SVEIKATOS TECHNOLOGIJOS VERTINIMAS: KRŪTIES ......nekontroliuojami ląstelių dariniai, bet jie neiplinta ir nėra pavojingi gyvybei, tačiau gali padidinti riziką susirgti krūties

SVEIKATOS TECHNOLOGIJOS VERTINIMAS:

KRŪTIES VĖŽIO DIAGNOSTIKA NAUDOJANT VAKUUMINĘ

KRŪTIES BIOPSIJĄ

HEALTH TECHNOLOGY ASSESSMENT:

VACUUM-ASSISTED BREAST BIOPSY IN THE DIAGNOSIS OF

BREAST CANCER

2017

VILNIUS

2

Valstybinė akreditavimo sveikatos priežiūros veiklai tarnyba

prie Sveikatos apsaugos ministerijos

Autoriai: Medicinos technologijų skyriaus vyr.specialistės:

Kristina Grigaitė

Vitalija Mazgelė

Valstybinė akreditavimo sveikatos priežiūros veiklai tarnyba prie Sveikatos apsaugos ministerijos

Jeruzalės g. 21, LT-08420 Vilnius

Tel. (8 5) 261 5177,

Faks. (8 5) 212 7310,

El. paštas: [email protected]

Sveikatos technologijos vertinimo santrauką galima rasti interneto svetainėje:

http://www.vaspvt.gov.lt/node/486

______________________________________________________________________________

State Health Care Accreditation Agency

under the Ministry of Health

Authors: Chief specialists of Medical Technology division:

Kristina Grigaitė

Vitalija Mazgelė

State Health Care Accreditation Agency under the Ministry of Health

Jeruzalės st. 21, LT-08420 Vilnius

Tel. (370 5) 261 5177,

Fax. (370 5) 212 7310,

E. mail: [email protected]

Health technology assessment is available on the website:


mailto:[email protected]


mailto:[email protected]


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TABLE OF CONTENTS

ABBREVIATIONS .................................................................................................................................. 5

SANTRAUKA ......................................................................................................................................... 6

Sveikatos technologijos vertinimo metodika ......................................................................................... 6

Tikslinė būklė......................................................................................................................................... 7

Tikslinė populiacija ................................................................................................................................ 8

Sveikatos priežiūros technologijos naudojimas ..................................................................................... 8

Šiuolaikinis būklės valdymas ................................................................................................................. 8

Kompensavimas ..................................................................................................................................... 9

Pagrindinės technologijos charakteristikos ............................................................................................ 9

Investicijos ir priemonės, reikalingos technologijos naudojimui ........................................................ 10

Pagrindinės alternatyvių technologijų charakteristikos ir referencinis standartas ............................... 10

Pacientų saugumas ............................................................................................................................... 10

Testo tikslumas .................................................................................................................................... 11

Su sveikata susijusi gyvenimo kokybė ir pacientų pasitenkinimas ..................................................... 12

SVEIKATOS TECHNOLOGIJOS FUNKCINĖ VERTĖ ..................................................................... 13

IŠVADOS ............................................................................................................................................... 14

REKOMENDACIJOS ............................................................................................................................ 15

SUMMARY ........................................................................................................................................... 16

Methodology of Health Technology Assessment ................................................................................ 16

Target Condition .................................................................................................................................. 17

Target Population ................................................................................................................................. 18

Utilisation of the VABB Technology .................................................................................................. 18

Current Management of the Condition ................................................................................................ 18

Regulatory Status ................................................................................................................................. 19

Features of the technology ................................................................................................................... 19

Investments and tools required to use the technology ......................................................................... 20

Features of the comparator and the reference Standard ....................................................................... 20

Patient safety ........................................................................................................................................ 20

Test accuracy ....................................................................................................................................... 21

Health-related quality of life and patient satisfaction .......................................................................... 22

HEALTH PROBLEM AND CURRENT USE OF THE VABB ........................................................... 24

Target Condition .................................................................................................................................. 24

Target Population ................................................................................................................................. 25

Utilisation of the VABB Technology .................................................................................................. 25

Current Management of the Condition ................................................................................................ 25

Regulatory Status ................................................................................................................................. 26

Discussion ............................................................................................................................................ 27

DESCRIPTION AND TECHNICAL CHARACTERISTICS OF THE VABB TECHNOLOGY ........ 28

Features of the VABB technology ....................................................................................................... 28

Claimed benefit of the VABB in relation to the comparators ......................................................... 29

Features of the comparator and the reference standard ....................................................................... 30

Comparators of the VABB technology ........................................................................................... 30

Reference standard of the VABB technology ................................................................................. 30

Investments and tools required to use the VABB technology ............................................................. 31

Training and information needed to use the VABB technology .......................................................... 31

Discussion ............................................................................................................................................ 32

SAFETY ................................................................................................................................................. 33

Adverse events ..................................................................................................................................... 33

False positive/ negative findings .......................................................................................................... 34

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Discussion ............................................................................................................................................ 35

CLINICAL EFFECTIVENESS ............................................................................................................. 36

Test accuracy ....................................................................................................................................... 36

Test accuracy according to imaging modality ................................................................................ 36

Test accuracy according to needle size ........................................................................................... 37

Test accuracy in comparison with alternative ................................................................................. 37

Health-related quality of life and patient satisfaction .......................................................................... 37

Discussion ............................................................................................................................................ 38

CONCLUSIONS .................................................................................................................................... 40

RECOMENDATIONS ........................................................................................................................... 41

REFERENCES ....................................................................................................................................... 42

APPENDIX 1: METHODS AND DESCRIPTION OF THE EVIDENCES USED ............................. 49

Reporting of results .............................................................................................................................. 49

Study characteristics ........................................................................................................................ 49

Patient characteristics ...................................................................................................................... 50

Quality assessment .......................................................................................................................... 50

Outcomes......................................................................................................................................... 51

APPENDIX 2: DOCUMENTATION OF THE BASIC SEARCH STRATEGIES .............................. 52

Flow charts of study selection.............................................................................................................. 53

APPENDIX 3: QUESTIONS USED FROM HTA CORE MODEL APPLICATION FOR

DIAGNOSTIC TECHNOLOGIES (Version 3.0) .................................................................................. 54

Health Problem and Current Use of the VABB Technology ............................................................... 54

Description and Technical Characteristics of the VABB Technology ................................................ 54

Safety ................................................................................................................................................... 54

Clinical Effectiveness .......................................................................................................................... 55

APPENDIX 4: DESCRIPTION OF THE EVIDENCE USED .............................................................. 56

Evidence tables of individual studies included .................................................................................... 56

APPENDIX 5: QUALITY ASSESSMENT OF SELECTED STUDIES .............................................. 65

Included studies ................................................................................................................................... 65

Excluded studies .................................................................................................................................. 66

Quality assessment ............................................................................................................................... 74

QUADAS-2 checklist for case series ................................................................................................... 78

The AMSTAR checklist for systematic reviews ................................................................................. 80

The IHE checklist for case series ......................................................................................................... 82

Checklist for potential ethical, organisational, social and legal aspects .............................................. 83

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ABBREVIATIONS

$ – dollar sign;

% – percent;

~ – approximately;

£ – pound sign;

€ – euro sign;

3D – three-dimensional;

BCa – breast cancer;

CE – Conformité Européene (European Conformity);

CNB – core needle biopsy;

DALYs – disability-adjusted life years;

DBT – Digital Breast Tomosynthesis;

DBT – digital breast tomosynthesis;

DCIS – ductal carcinoma in situ;

e.g. – for example;

ESMO – European Society of Medical Oncology;

etc. – et cetera;

FDA – Food and Drug Administration;

FN – false negative;

FP – false positive;

G – French gauge;

ICa – infiltrating cancer;

ICD-10 (TLK-10-AM) – International Classification of Diseases, 10th Revision;

IDC – invasive ductal carcinoma;

IHME – Institute of Health Metrics and Evaluation;

ILC – invasive lobular carcinoma;

lsns. – lesions;

Med. – median;

MIBB group – Minimally Invasive Breast Biopsies Working Group;

MMx – digital mammography;

MRI – magnetic resonance imaging;

MRI-VABB – magnetic resonance imaging-guided vacuum-assisted breast biopsy;

n – number;

NPV – negative predictive value;

PPV – positive predictive value;

pts. – patients;

QoL – quality of life;

S – stereotactic;

S-VABB – stereotactic-guided vacuum-assisted breast biopsy;

TMI – Testing Morbidities Index questionnaire

TNM – cancer staging system (tumour–node–metastases).

US – ultrasound;

USA – the United States of America;

US-FNA – ultrasound-guided fine needle aspiration;

US-VABB – ultrasound-guided vacuum-assisted breast biopsy;

VABB – vacuum-assisted breast biopsy;

vs. – versus;

WHO – World Health Organization.

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SANTRAUKA

Sveikatos technologijos vertinimo metodika

Vertinimas atliktas remiantis tarptautinio Europos sveikatos technologijų vertinimo tinklo

„EUnetHTA“ parengta sveikatos technologijų vertinimo metodika. VABB diagnostinės technologijos

vertinimo analizė atlikta remiantis mokslinės literatūros šaltiniais, esančiais:

• The Cochrane Library duomenų bazėje;

• PubMed (Medline) duomenų bazėje;

• CRD duomenų bazėje;

• Gamintojų internetiniuose puslapiuose, kurių ieškota rankiniu būdu viešai prieinamoje

erdvėje (internete).

Sisteminė literatūros paieška buvo tikslinama naudojant duomenų filtrą – publikacijos

publikuotos 5 metų laikotarpiu nuo 2012 m. Sisteminės literatūros paieškos strategija pateikta 2 priede.

Straipsniai, susiję su „Saugumo“ ir „Klinikinio efektyvumo“ skyriais, buvo atrinkti VASPVT

(Valstybinė akreditavimo sveikatos priežiūros veiklai tarnyba prie Sveikatos apsaugos ministerijos,

Lietuva) Medicinos technologijų skyriaus specialistų. Siekiant pagerinti paieškos jautrumą,

diagnostinių tyrimų filtras nebuvo naudojamas. Papildomai, siekiant patvirtinti paieškos strategijos

tinkamumą, ieškota sisteminių apžvalgų, peržiūrėti jų literatūros sąrašai. Papildomi moksliniai

straipsniai buvo įtraukti arba atmesti vadovaujantis PICO lentele, kuri pateikta santraukoje.

Atsakant į „Klinikinio efektyvumo“ ir „Saugumo“ skyrių klausimus, nebuvo rasta sveikatos

technologijų vertinimų ar randomizuotų kontroliuojamų tyrimų; buvo remtasi rastomis sisteminėmis

literatūros apžvalgomis bei prospektyviniais ir retrospektyviniais nekontroliuojamais tyrimais.

Atsakant į „Sveikatos problema ir dabartinis technologijos naudojimas“ bei „Techninės

charakteristikos“ skyrių klausimus, į vertinimą įtrauktiems tyrimams jokie apribojimai netaikyti.

Pritrūkus informacijos prieš tai minėtuose literatūros šaltinių tipuose ir negalint atsakyti į kai

kuriuos „Sveikatos problema ir dabartinis technologijos naudojimas“ bei „Techninės charakteristikos“

skyrių klausimus, rankiniu būdu (internete) buvo vykdomos papildomos paieškos specifiniuose

literatūros šaltiniuose (medicininių rekomendacijų duomenų bazėse, gamintojų internetiniuose

puslapiuose ir kt.).

Vertinime naudojamų technologijos diagnostinį tikslumą vertinančių tyrimų kokybė buvo

įvertinta specialiu „QUADAS-2“ klausimynu (žr. Priedas 5). Klausimynas vertina tyrimų kokybę

keturiose srityse: pacientų atranka, indekso testas, referencinis standartas, tyrimo eiga ir laikas.

Atskirai kiekviena sritis (domenas) yra vertinama atsižvelgiant į neatsitiktinių klaidų riziką, taip pat

pirmieji trys domenai vertinami taikymo problemos atžvilgiu. Klausimyno kiekvienos srities

neatsitiktinių klaidų rizikos rezultatai klasifikuojami į „žema“, „neaiški“ ir „aukšta“. Vertinime

naudojamų sisteminių literatūros apžvalgų kokybė buvo patikrinta specialiu, sisteminėms literatūros

apžvalgoms skirtu, „AMSTAR“ kontrolės klausimynu (žr. Priedas 5). Be to, trijų tyrimų (vienas

tyrimas įtrauktas į „Saugumo“ skyrių, kiti du – į „Klinikinio efektyvumo“ skyriaus poskyrį apie

gyvenimo kokybę ir pacientų pasitenkinimą) kokybė buvo tikrinta specialiu, nekontroliuojamiems

tyrimams skirtu, Sveikatos Ekonomikos instituto kontrolės klausimynu (angl. The IHE checklist) (žr.

Priedas 5).

Atrinktų tyrimų bei juose analizuojamų populiacijų pagrindinės charakteristikos ir rezultatai,

susiję su klinikiniu efektyvumu bei saugumu, pateikti lentelėse (žr. Priedas 4).

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PICO lentelė

Populiacija Įvairaus amžiaus moterys, kurioms įtariami:

• Pirminiai didelės rizikos/ piktybiniai krūties dariniai (B3–B5);

• Mikrokalcifikatai (B2);

• Dariniai, matomi tik su magnetiniu rezonansu.

MeSH: Breast Neoplasms (C04.588.180, C17.800.090.500).

Intervencija Vakuuminė krūties biopsija (VABB) kartu su naudojama ultragarso (US-

VABB), rentgeno (mamografo) (S-VABB) ar magnetinio rezonanso (MRI-

VABB) vaizdinimo priemone.

MeSh terms: Biopsy (E01.370.225.500.384.100, E01.370.225.998.054, E01.370.388.100, E04.074,

E05.200.500.384.100, E05.200.998.054, E05.242.384.100); Image-Guided Biopsy

(E01.370.225.500.384.100.370, E01.370.225.998.054.370, E01.370.388.100.370, E04.074.370,

E05.200.500.384.100.370, E05.200.998.054.370, E05.242.384.100.370); Mammary Ultrasonography

(E01.370.350.850.860, E01.370.378.850); Interventional Ultrasonography (E01.370.350.850.855,

E04.502.890); X-Ray Tomography (E01.370.350.700.810, E01.370.350.825.810); Magnetic Resonance

Imaging (E01.370.350.825.500). Alternatyvos • Histologinė/ chirurginė biopsija;

• Stulpelinė biopsija;

• Aspiracinė punkcija.

MeSH terms: Surgical Pathology (H02.403.650.510); Biopsy (E01.370.225.500.384.100,

E01.370.225.998.054, E01.370.388.100, E04.074, E05.200.500.384.100, E05.200.998.054,

E05.242.384.100); Image-Guided Biopsy (E01.370.225.500.384.100.370, E01.370.225.998.054.370,

E01.370.388.100.370, E04.074.370, E05.200.500.384.100.370, E05.200.998.054.370,

E05.242.384.100.370); Needle Biopsy (E01.370.225.500.384.100.119, E01.370.225.998.054.119,

E01.370.388.100.100, E04.074.119, E04.665.100, E05.200.500.384.100.119, E05.200.998.054.119,

E05.242.384.100.119); Fine Needle Biopsy (E01.370.225.500.384.100.119.500,

E01.370.225.998.054.119.500, E01.370.388.100.100.500, E04.074.119.500, E04.665.100.500,

E05.200.500.384.100.119.500, E05.200.998.054.119.500, E05.242.384.100.119.500).

Rezultatai

Efektyvumas

1) Diagnostinis tikslumas (specifiškumas, jautrumas);

2) Ligai specifinis mirštamumas, Ligai specifinis sergamumas;

3) Gyvenimo kokybė.

Saugumas

1) Nepageidaujami įvykiai;

2) Klaidingai neigiami/ Klaidingai teigiami radiniai.

PICO klausimas: Ar vakuuminė krūties biopsija įvairaus amžiaus moterims, kurioms įtariami

pirminiai didelės rizikos ar piktybiniai krūties dariniai, mikrokalcifikatai, tik su magnetiniu

rezonansu matomi dariniai, yra efektyvesnė ir saugesnė negu alternatyvūs diagnostiniai metodai,

atsižvelgiant į diagnostinį tikslumą, terapinį poveikį, ligai specifinį mirštamumą ir sergamumą,

gyvenimo kokybę ir nepageidaujamus įvykius?

Tikslinė būklė

Krūties vėžys prasideda, kai krūties ląstelės pradeda nekontroliuojamai augti, o jų perteklius

kaupiasi į darinį ar sluoksnį, vadinamą augliu arba naviku, kurį dažniausiai galima apčiuopti arba

galima pamatyti rentgeno pagalba (mamografijos metu). Gerybiniai krūties navikai taip pat yra

nekontroliuojami ląstelių dariniai, bet jie neišplinta ir nėra pavojingi gyvybei, tačiau gali padidinti

riziką susirgti krūties vėžiu. Navikas yra piktybinis (vėžinis), jei ląstelės gali peraugti aplinkinius

audinius ar plisti (metastazuoti) į kitus organus. Pagal Tarptautinę statistinę ligų ir sveikatos sutrikimų

klasifikaciją (TLK-10-AM) krūties navikai apibrėžiami kaip Krūties piktybinis navikas (pagal TLK-

10-AM: C50), Krūties karcinoma in situ (pagal TLK-10-AM: D05) ir Krūties gerybinis navikas (pagal

TLK-10-AM: D24). (A0002)

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Pagrindiniai krūties vėžio atsiradimo rizikos veiksniai: lytis, vyresnis amžius, paveldimumas

(dažniausiai genai BRCA1 ir BRCA2), estrogenų poveikis (endogeninis ir egzogeninis), krūties

audinio tankumas, kai kurios gerybinės krūties ligos (dažniausiai atipinė hiperplazija), jonizuojanti

spinduliuotė, alkoholis, nepakankamas fizinis aktyvumas, antsvoris ar nutukimas. (A0003)

Kai navikas yra mažas ir lengviausiai gydomas krūties vėžys paprastai nesukelia jokių

simptomų. Dėl tokių priežasčių yra labai svarbu, kad moterys tikrintųsi pagal rekomenduojamą tvarką

ir krūties vėžys būtų aptinkamas ankstyvosiose stadijose. Retesni simptomai ir požymiai yra: krūties

skausmas ar sunkumas; nuolatiniai krūties pokyčiai (pvz., patinimas, sustorėjimas, krūties odos

paraudimas; krūties spenelio pakitimai (pvz., atsiradęs skystis (ypač kruvinas), erozija, įtraukimas).

Svarbu pažymėti, jog krūties skausmas nėra reikšmingas krūties vėžio simptomas – sveikų moterų

krūtys gali būti skausmingos priklausomai nuo ciklo. (A0004; A0005)

Pagal IHME duomenis, 2015 metais 195 valstybėse krūties vėžio sukeltos negalios prarasti

sveiko gyvenimo metai (DALYs) siekė 15.1 mln. metų. Lietuvoje 2011 metais vidutinė vieno paciento

tiesioginių išlaidų dalis, skirta krūties vėžio atvejui, buvo apie 2580 €; vidutinė tiesioginių išlaidų dalis

skyrėsi priklausomai nuo krūties vėžio stadijos: nuo 2409 € pirmojoje stadijoje iki 3688 € ketvirtojoje

stadijoje. (A0006)

Tikslinė populiacija

Jaunesnių nei 40 m. amžiaus moterų krūties vėžio dažnis yra mažesnis – krūties vėžio rizika

didesnė vyresnėms nei 50 m. moterims, o su amžiumi rizika dar didėja. (A0007)

2012 m. (paskutinių metų prieinami duomenys) krūties vėžys buvo antras iš visų dažniausiai

diagnozuojamų vėžių (abiems lytims): 12% visų diagnozuotų vėžių (1.7 mln. gyventojų) ir penkta

dažniausia mirties priežasties (abiems lytims): 6% visų mirčių dėl vėžių (522,00 gyventojų). Krūties

vėžys yra pagrindinė moterų mirties dėl vėžio priežastis mažiau išsivysčiusiuose regionuose (324,000

mirčių, 14.3% nuo visų mirčių), ir antra moterų mirties dėl vėžio priežastis labiau išsivysčiusiuose

regionuose (198,000 mirčių, 15.4% nuo visų mirčių). Nepaisant aukšto sergamumo Vakarų šalyse, dėl

ankstyvo krūties vėžio nustatymo ir gydymo apie 89% moterų išgyvena 5 m. po krūties vėžio

diagnozės. (A0023)

Lietuvoje krūties vėžys yra dažniausiai pasitaikanti moterų vėžio rūšis: kasmet naujai

diagnozuojamas apie 2500 moterų ir apie 550 moterų kasmet miršta dėl krūties vėžio. 2015 metais

Lietuvoje dėl krūties vėžio (pagal TLK-10-AM: C50) mirė 576 moterys, o ligotumas siekė 7.9

atv./1000 moterų. Duomenys apie gerybinius krūties navikus yra neaiškūs dėl duomenų sujungimo

statistinėse formose. (A0023)

Sveikatos priežiūros technologijos naudojimas

Vakuuminė krūties biopsija (VABB) – audinių mėginių ėmimo metodas, kai naudojamas

specialus vakuuminis prietaisas ir vaizdinimo priemonė, ir kai per vieną dūrį galima paimti audinių iš

visos zonos. Tai mažiau invazinė priemonė negu atvira chirurginė biopsija, tačiau ne visais atvejais

galima taikyti VABB. (A0001; F0001)

Pasaulinė krūties biopsijų (visų tipų ir lokacijų) rinka nuo 409,2 mln. € (2015 m.) pasieks apie

683.3 mln. € (2020 m.). Atsižvelgiant į Akreditavimo tarnybai pateiktą paraišką, VABB (gamintojas:

EnCor®) kaina Lietuvoje siekia apie 91,000 €; papildomai kasmetinės tiesioginės ir netiesioginės

išlaidos gali siekti dar apie 67,000 €. (A0011)

Šiuolaikinis būklės valdymas

Krūties vėžio diagnozė nustatoma remiantis klinikinės apžiūros, vaizdinimo priemonių ir

patologinio įvertinimo rezultatais. Patologinė diagnostika turėtų būti grindžiama biopsija, kuri

atliekama kartu su ultragarso ar rentgeno vaizdinėmis priemonėmis. Galutinė patologinė diagnozė

9

pateikiama pagal Pasaulio sveikatos organizacijos klasifikaciją ir pagal naviko-limfmazgių-metastazių

(TNM) klinikinę klasifikaciją. Papildomai turi būti įvertinama: asmens sveikatos istorija; šeimos

istorija, susijusi su krūties/ kiaušidžių vėžiais ir kitomis vėžio formomis; fizinė būsena; kraujo ląstelių,

kepenų ir inkstų funkcijos tyrimas; šarminės fosfatazės ir kalcio kiekis. (A0024)

Daugelis Europos valstybių yra patvirtinusios nacionalines ar regionines moterų patikros

programas, kuriomis siekiama dar priešklinikinėje stadijoje mamografijos tyrimo metu nustatyti

krūties vėžį. Siekiant užtikrinti krūties vėžio patikrą ir diagnostiką, Europos gairėse yra

rekomenduojama stebėti tam tikrus veiklos parametrus ir rodiklius. Mamografinė patikra, atliekama

kas 2 metus, parodė didžiausią mirtingumo mažinimo naudą 50–69 metų moterims ir yra

rekomenduojama tiek Europos Sąjungos, tiek kitų šalių. (A0025)

Kompensavimas

Klinikinėje praktikoje dažniausiai yra naudojami šie VABB prietaisai: VaCora® (CR Bard,

Inc., Covington, GA, USA), EnCor® (EnCor® MR, SenoRx, Allso Viejo, CA, USA), Mammotome®

(Ethicon Endo-surgery, Inc., Cincinnati, Ohio, USA) ir ATEC® (Suros Surgical Systems, Inc.,

Indianapolis, USA). Visi prietaisai turi tiek CE ženklą, tiek yra patvirtinti JAV Maisto ir vaistų

administracijoje (FDA). (A0020; A0022)

VABB metodas kai kuriose šalyse (Prancūzija, JAV) yra visiškai arba dalinai

kompensuojamas. Lietuvos Nacionalinis vėžio institutas vakuuminei krūties biopsijai reikalingas datas

įsigyja rėmėjų dėka, o valstybė kompensuoja tik dalį tokių procedūrų. (A0021)

Pagrindinės technologijos charakteristikos

Vakuuminės krūties biopsijos (VABB) technologija, leidžianti manipuliuoti adata 360°

kampu ir vieno dūrio metu paimti ne vieną bioptatą, buvo sukurta ir pristatyta devintajame praėjusio

amžiaus dešimtmetyje (~1995 m.). Pirmoji VABB (su Mammotome® sistema) atlikta 1995 m.

rugpjūčio mėn. Denveryje, JAV; nuo 1996 m. ši technologija naudojama Europoje. Rinkoje yra 4-ių

gamintojų prietaisai, skirti vakuuminei biopsijai atlikti su skirtingo dydžio adatomis (7–14G):

Mammotome®, EnCor®, ATEC®, VaCora®; šios sistemos turi keletą skirtingų modelių. Visos

sistemos gali būti naudojamos trimis būdais – rentgeno kontrolėje (mamografija) (S), ultragarso

kontrolėje (US) arba magnetinio rezonanso kontrolėje (MRI), tačiau tik naudojantis ultragarsiniu

prietaisu procedūra vyksta esamuoju laiku (bioptatų paėmimas matomas ultragarsinio prietaiso

monitoriaus ekrane). (B0001; B0003)

Ši biopsija yra minimaliai invazinė procedūra, ją lyginant su chirurgine biopsija, po VABB

pasiekiamas geresnis kosmetinis rezultatas, trumpesnė procedūros trukmė, mažesnė vidinių randų

tikimybė. Procedūra paprastai trunka apie 30–60 min., po jos pacientas gali būti išleidžiamas namo.

Tai įrodo, jog atliekant VABB yra mažesnės laiko ir ekonominės išlaidos, kadangi chirurginė biopsija

trunka 1–2 val., reikalingas pooperacinis periodas, kad pacientas atsigautų po nejautros.

VABB metu paimami audinių mėginiai yra didesni ir pakanka vieno dūrio; lyginant su

stulpeline biopsija (CNB), reikia atlikti 4–6 adatos dūrius, norint paimti pakankamą biopsinės

medžiagos kiekį. Procedūros metu prasidėjus kraujavimui, VABB technologija turi kraują siurbiančią

funkciją. Dar vienas technologijos privalumas – ji gali būti taikoma terapiniais tikslais nedidelių

nepiktybinių krūties darinių, pvz., fibroadenoma, šalinimui. (B0002; B0001)

Sveikatos priežiūros įstaiga, kurioje bus atliekama VABB priklauso nuo vaizdinimo prietaisų,

kurie bus naudojami per procedūrą (mamografas, ultragarsinis prietaisas, magnetinio rezonanso

tomografas). VABB su mamografu arba ultragarsiniu prietaisu gali būti atliekama ambulatorinėmis

sąlygomis taikant vietinę nejautrą, dalyvaujant radiologui ar patyrusiam specialistui. VABB su MRI

atliekama tik tose gydymo įstaigose, kurios turi šį prietaisą. (B0004)

https://www.google.lt/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&cad=rja&uact=8&ved=0ahUKEwinmPqYw8rOAhXDVBQKHYBUDSEQFggqMAE&url=http%3A%2F%2Fwww.bardbiopsy.com%2Fproducts%2Fencor.php&usg=AFQjCNFmTa_OdlfrzsW94zav-WxUmiybPw&bvm=bv.129759880,d.d24

https://www.google.lt/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&cad=rja&uact=8&ved=0ahUKEwiEnoHFwsrOAhVB7xQKHWBeCvEQFggjMAE&url=http%3A%2F%2Fwww.bardbiopsy.com%2Fproducts%2Fvacora_video.php%3Fi%3Dmri&usg=AFQjCNHVMMS8BhRQwh5No8Jz0sL1m8AB-Q

10

Investicijos ir priemonės, reikalingos technologijos naudojimui

Laisvai pastatomas pultas (angl. console) užtikrina vakuumo funkciją (išskyrus VaCora®

sistema); atliekant MRI-VABB, pultas negali būti toje pačioje patalpoje dėl magnetinio lauko

poveikio. Priklausomai nuo skirtingų VABB technologijos gamintojų, procedūras atliekant su

skirtingais vaizdinimo prietaisais reikia ir skirtingo pultų skaičiaus: ATEC® sistemai pakanka vieno

pulto ir mamografui, ir ultragarsiniam prietaisui, ir MRI, EnCor® sistemai reikia dviejų pultų,

Mammotome® sistemai reikia trijų skirtingų pultų. Pultas plastikiniais vamzdeliais sujungtas su

biopsiniu zondu (adata), ant kurio yra biopsinės adatos nukreipėjas. Biopsiniai zondai su adatomis,

plastikinių vamzdelių rinkiniai, „atliekų“ kanistrai (angl. debris canisters), biopsinės medžiagos

surinkimo talpa, visos šios dalys yra vienkartinės. Procedūrai atlikti reikalingi ir specialūs gulimieji

arba sėdimieji biopsiniai stalai. Papildomai kiekvienai procedūrai reikalingos šios vienkartinės

priemonės: krūties audinio žymeklis, skalpelis, sterilios pirštinės, sterili tvarsliava, talpa su 10%

formalino tirpalu biopsinei medžiagai, švirkštai ir adatos, medicininis ultragarsinis gelis (US-VABB) ir

pan. (B0009)

Remiantis specialistų konsensuso rekomendacijomis kaip atlikti S-VABB (Vokietijos

senologų draugija) (angl. Interdisciplinary Consensus Recommendations for the use of Vacuum-

Assisted Breast Biopsy under Sonographic Guidance (German Society of Senology)), specialisto

kvalifikacijai įgyti reikalingi specialūs kursai; po kursų, pirmosios 10 procedūrų turi būti atliekamos

stebint VABB ekspertui. Remiantis Europos krūtų vaizdinimo draugija (angl. The European Society of

Breast Imaging), prieš atliekant VABB su MRI, reikia atlikti 20 mokomųjų procedūrų su patyrusių

specialistų priežiūra; norint neprarasti kompetencijos, rekomenduojama atlikti mažiausiai 25 MRI-

VABB per metus. (B0013)

Pagrindinės alternatyvių technologijų charakteristikos ir referencinis standartas

Nuo 1968 m. atliekama aspiracinė punkcija ilgai buvo laikoma funkcionaliausiu metodu

nustatant kietų darinių krūtyje kilmę. Aspiracinės punkcijos metu plona punktuojamąja adata

praduriama krūties oda ir švirkštu paimama darinio ląstelių arba skysčio. Ilgainiui, susiduriant su šio

metodo trūkumais, aspiracinę punkciją ėmė keisti stulpelinė biopsija, kurios pagrindinis privalumas –

histologinio mėginio paėmimas. Vieno dūrio metu paimamas vienas bioptatas, tačiau norint paimti

pakankamą biopsinės medžiagos kiekį reikalingi 4–6 adatos dūriai. Tiek aspiracinė punkcija, tiek

stulpelinė biopsija yra minimaliai invazinės procedūros atliekamos ambulatorinėmis sąlygomis,

pacientų gerai toleruojamos ir greitos. (B0003; B0001; B0004)

Chirurginė biopsija ilgą laiką buvo vadinama „auksiniu standartu“ ar „referenciniu standartu“

diagnozuojant krūties vėžį, ypač tais atvejais, kai įtariamai navikinį darinį sunku pasiekti su biopsine

adata. Dabartinėje praktikoje kiti biopsijų metodai (su skirtingais vaizdinimo prietaisais) iš dalies, bet

ne visiškai, pakeitė chirurginę biopsija. Chirurginė biopsija dabar dažniausiai taikoma, kai su kitų rūšių

biopsijomis nepavyksta nustatyti diagnozės, tačiau specialistams abejonė išlieka. Procedūros metu,

kuri atliekama su bendrąja arba vietine nejautra, įtariamai navikinis darinys pažymimas metaline viela.

Chirurgas atlieka pjūvį, pašalina vielą ir visą pažymėtą krūties audinių sektorių (paprastai golfo

kamuoliuko dydžio), po to seka histologinis audinių ištyrimas diagnozei nustatyti. (B0001; B0004)

Pacientų saugumas

Nepageidaujami įvykiai, susiję su VABB procedūra, nurodyti 7-iuose į vertinimą įtrauktuose

tyrimuose (n=2697). Išskirtos trys nepageidaujamų įvykių grupės: susiję su prietaisu ir/ arba

procedūra, gyvybei keliantys grėsmę (pavojingi) ir gyvybei nepavojingi. (C0008; C0004)

Vienintelis su prietaisu ir/ arba procedūra susijęs nepageidaujamas įvykis buvo intraoperacinis

kraujavimas; jis buvo nurodytas 3-uose tyrimuose, atvejų dažnis varijavo nuo 0.5% iki 21.3%. Nors

dažnis gana aukštas, reikia pastebėti, jog didžiają atvejų dalį (17.4%) sudarė lengvo pobūdžio

kraujavimas. Pavojingų nepageidaujamų įvykių grupėje buvo infekcija, hematoma, dėl kurios prireikė

11

chirurginės intervencijos, vidutinė/ didelė hematoma ir vidutinis/ didelis randas vidiniuose audiniuose;

šios komplikacijos buvo nurodytos 3-uose tyrimuose, atvejų dažnis varijavo nuo 0% iki 6.2%. Gyvybei

nepavojingos komplikacijos – odos kraujosruvos, nedidelės hematomos, nedideli vidinių audinių

randai – nurodytos 6 tyrimuose; atvejų dažnis varijavo nuo 1.1% iki 41.3%. (C0008; C0004)

Vienas tyrimas palygino VABB procedūras, kurios buvo atliktos 178 pacientams su

skirtingomis S-VABB sistemomis (Mammotome® ir ATEC®) ir skirtingais adatų dydžiais (8G, 9G,

11G, 12G). Tyrimo tikslas – įvertinti, kada dažniau įvyksta intraoperacinis kraujavimas, hematoma ar

susiformuoja randas. Rezultatai parodė, jog intraoperacinis kraujavimas (p<0.001) ir pooperacinė

hematoma (p=0.029) statistiškai reikšmingai dažniau susiformuoja procedūras atliekant su didesnio

diametro adatomis (11G vs. 8G), kai buvo naudojama Mammotome® sistema, tačiau statistinio

reikšmingumo nebuvo naudojant didesnes adatas (12G vs. 9G) su ATEC® sistema. Be to, su

Mammotome® sistemos mažesnio diametro (11G) adatomis buvo nustatyta statistiškai reikšmingai

mažiau kraujavimo (p=0.015)/ hematomų (p=0.001) atvejų, lyginant su ATEC® sistemos 12G dydžio

adatomis; statistiškai reikšmingi skirtumai su didesnėmis adatomis (8G ir 9G) nenustatyti. Statistiškai

reikšmingo ryšio, tarp randų susidarymo, VABB sistemos ir adatos dydžio, nebuvo. (C0004)

Viename į vertinimą įtrauktame tyrime daliai pacientų buvo atlikta CNB, tačiau jokie

nepageidaujami įvykiai nenurodyti; nė viename tyrime nebuvo nurodyti nepageidaujami įvykiai susiję

ir su referenciniu standartu. (C0008)

Dažniausios su VABB susijusios komplikacijos – intraoperacinis kraujavimas ir hematomos.

Stengiantis sumažinti šių nepageidaujamų atvejų dažnį, prieš VABB pacientams rekomenduojama

pakoreguoti dozę ar visiškai nutraukti gydymą antikoaguliantais. Iš karto po procedūros, intervencijos

vieta yra sutvarstoma, tikintis, jog spaudimas užtikrins hemostazę. (C0007; C0062)

Klaidingai teigiamos/ neigiamos reikšmės buvo nurodytos 16-oje tyrimų (iš 19-os). Visuose

tyrimuose klaidingai teigiamų atvejų dažnis lygus 0%. Taip yra todėl, kad VABB pašalina daug

įtariamai navikinio audinio ir po VABB atliekant chirurginę biopsiją galima gauti priešingus rezultatus

– be vėžinių ląstelių; chirurginės biopsijos rezultatai gali prieštarauti indekso testo rezultatams. Vis

dėlto, VABB patvirtinus krūties vėžį, tokie rezultatai laikomi teisingai teigiamais, vietoj klaidingai

teigiamų, nes manoma, jog visos vėžinės ląstelės buvo pašalintos per VABB procedūrą. Klaidingai

neigiamų atvejų dažnis tyrimuose varijavo nuo 0% iki 23.2%. (C0006)

Klaidingai neigiamų reikšmių dažnį analizuojant pagal tai, su kokia vaizdinimo priemone

atlikta VABB, buvo nustatyta: klaidingai neigiamų atvejų dažnis su US-VABB po chirurginės

biopsijos buvo lygus 1.3% (2 iš 152 pacientų); su S-VABB klaidingai neigiamų atvejų dažnis varijavo

nuo 0% iki 19.4% (114 iš 589 pacientų); su MRI-VABB – nuo 6% (4 iš 67 pacientų) iki 23.2% (16 iš

69 pacientų). Su CNB klaidingai neigiamų reikšmių dažnis buvo aukštesnis nei su VABB – 42.1% (8

iš 19 pacientų) vs. 9.1% (1 iš 11 pacientų). (C0006)

Klaidingi diagnostinių tyrimų rezultatai gali daryti neigiamą įtaką paciento būklei. Yra

moksliškai įrodyta, jog klaidingai teigiami tyrimo rezultatai pasireiškia nuolatiniu susirūpinimu ir

baime dėl diagnozuotos ligos. Taip pat gali būti susiję su nereikalingu papildomos biopsinės

procedūros atlikimu, nereikalingo gydymo taikymu ir didesnėmis ekonominėmis išlaidomis. Dėl

klaidingai neigiamų tyrimo rezultatų pacientui gali būti nesuteiktas reikalingas gydymas. (C0006)

Testo tikslumas

Testo tikslumas remiasi vienpusiais tyrimais, kuriuose lyginami indekso testo (VABB) ir

referencinio standarto (chirurginė biopsija) rezultatai. Manoma, kad chirurginė biopsija yra 100%

patikimas metodas, vis dėlto praktikoje patikimumas gali būti mažesnis. (D1003)

Bendras VABB jautrumas svyravo nuo 0% iki 100%: septyniuose tyrimuose jautrumas buvo

0%, o trijuose – 100%. Vis dėlto, šešiuose tyrimuose VABB jautrumas svyravo nuo 88.9% iki 98.4%.

Bendras VABB specifiškumas visuose 16 įtrauktų tyrimų buvo 100%. Teigiama prognostinė vertė

svyravo nuo 0% iki 100%, o neigiama prognostinė vertė (NPV) – nuo 75.7% iki 100%. Bendras

krūties vėžio neįvertinimo rodiklis svyravo nuo 0% iki 23.2% (nuo 0 iki 114 pacientų tyrimuose buvo

klasifikuoti kaip nesergantys krūties vėžiu (pagal TLK-10-AM: C50 arba D05)), tačiau dažniausiai

12

neįvertinimo rodiklis tyrimuose buvo nuo 0% iki 7.6% (nuo 0 iki 16 pacientų buvo klasifikuoti kaip

nesergantys krūties vėžiu). (D0020; D0029; D1001; D1006; D1019)

VABB buvo atliekamas su trimis skirtingomis vaizdinimo sistemomis (ultragarsas, rentgenas

ir magnetinio rezonanso tomografas). Jautrumas svyravo nuo 0% iki 100% visoms vaizdinimo

sistemoms, tačiau S-VABB jautrumas daugiausiai buvo nuo 89.2% iki 94.7%, MRI-VABB – 0%, o

US-VABB – 98.4%. Visų vaizdinimo sistemų specifiškumas – 100%. Visų vaizdinimo sistemų PPV

svyravo nuo 0% iki 100%, tačiau 4/5 tyrimai nurodė, kad S-VABB PPV yra 100%, o 3/4 tyrimai

nurodė, kad MRI-VABB reikšmė yra 0%. S-VABB neigiama prognostinė vertė buvo nuo 80.6% iki

100%, MRI-VABB – 76.8% iki 94%, o US-VABB apie 93.3%. Krūties vėžio neįvertinimo rodiklis

pagal vaizdinimo sistemas buvo: US-VABB – 1.3% (2 iš 152 pacientų buvo neteisingai klasifikuoti

kaip nesergantys krūties vėžiu), S-VABB – 10.9% (155 iš 1419 pacientų), o MRI-VABB – 15.2% (56

iš 368 pacientų). (D1006; D1007; D1019)

VABB procedūra buvo atliekama naudojant įvairių diametrų adatas (7G, 8G, 9G – didelio

skersmens, ir 10G, 11G, 12G, 13G – mažo skersmens). Didelio skersmens adatų jautrumas svyravo

nuo 0% iki 91.5%, tačiau dažniausiai svyravo apie 88.9–91.5%. Mažo skersmens adatų jautrumas

svyravo nuo 0% iki 100%, tačiau dažniausiai svyravo apie 89.2–98.4%. Specifiškumas abiejose

grupėse buvo 100%. PPV abiejose grupėse svyravo nuo 0% iki 100%, tuo tarpu NPV didelio

skersmens grupėje buvo 75.7–94%, o mažo skersmens – 80.6–100% (daugeliu atvejų NPV buvo 80.6–

93.3%). Krūties vėžio neįvertinimo rodiklis pagal didelį ir mažą adatų diametrus atitinkamai buvo

9.1% (76 iš 834 pacientų buvo neteisingai klasifikuoti kaip nesergantys krūties vėžiu) ir 10.6% (148 iš

1400 pacientų). (D1006; D1007; D1019)

Viename retrospektyviniame tyrime VABB rezultatai buvo lyginami su CNB rezultatais.

Pacientai buvo suskirstyti į dvi grupes, kur 11 pacientų buvo atlikta VABB (9 iš 11 pacientų taip pat

buvo atlikta CNB) ir 19 pacientų buvo atlikta CNB (9 iš 19 taip pat buvo atlikta VABB). VABB ir

CNB metodų jautrumas atitinkamai buvo 83.3% ir 0%, specifiškumas – 100%, PPV atitinkamai 100%

ir 0%, NPV atitinkamai – 83.3% ir 57.9%. Krūties vėžio neįvertinimo rodiklis VABB siekė 9.1% (1 iš

11 pacientų buvo neteisingai klasifikuotas kaip nesergantis krūties vėžiu), o CNB – 42.1% (8 iš 19

pacientų). (D0020; D1002)

Su sveikata susijusi gyvenimo kokybė ir pacientų pasitenkinimas

Dviejuose tyrimuose pagrindinis tikslas buvo ištirti gyvenimo kokybės ir pacientų

pasitenkinimo VABB procedūra rezultatus. Viename perspektyviniame tyrime aprašyta 90 moterų

VABB patirtis ir trumpalaikės pacientų gyvenimo kokybės pokyčiai. Šiuo atveju skaitmeninė krūtų

tomosintezė (S-VABB (DBT)) buvo blogiau toleruojama (blogesnė VABB patirtis skausmo,

diskomforto, baimės, nerimo, fizinės ir psichinės funkcijos aspektais) negu skaitmeninė mamografija

(S-VABB (MMx)), tačiau bendras pasitenkinimas procedūra ir drovėjimasis (varžymasis) tyrimo metu

buvo panašus abiejose pacientų grupėse. (D0012; D0017)

Kitame retrospektyviniame tyrime lyginamos dviejų gamintojų VABB sistemos (150 pacientų

VABB atlikta su ATEC® (9G adata), o 39 pacientams – su Mammotome® (11G adata) sistema).

Nebuvo nustatyta reikšmingo skirtumo tarp dviejų VABB sistemų, kai lyginama paciento būklė tyrimo

metu (p=0.25) ir po jo (p=0.2). Vis dėlto, ATEC® sistema buvo dažniau negu Mammotome® susijusi

su pacientų pranešamomis komplikacijomis (p=0.005; 41.3% ir 17.9%). Abiejose grupėse (ATEC® ir

Mammotome®) pacientai buvo pakankamai patenkinti kosmetiniais rezultatas po biopsijos (97.3% ir

97.4%) ir, prireikus, vėl rinktųsi VABB procedūrą (88% ir 92.3% atitinkamai), o ne chirurginę

biopsiją. (D0012; D0017; D0029)

Vis dėlto, abiejuose tyrimuose gyvenimo kokybės ir bendro pasitenkinimo procedūra balai

buvo mažesni jaunesnio amžiaus moterų grupėse; jaunesnės moterys dažniau pranešdavo apie

įvykusias komplikacijas (p=0.02). Be to, pacientai, kuriems diagnozuotas piktybinis krūties navikas,

statistiškai reikšmingai blogiau vertino VABB procedūrą: savo būklę per procedūrą (p=0.011), savo

būklę po procedūros (p=0.035) bei kosmetinį rezultatą po biopsijos (p=0.024). (D0012; D0017;

D0029)

13

SVEIKATOS TECHNOLOGIJOS FUNKCINĖ VERTĖ

Vadovaujantis Ligų, vaistinių preparatų ir medicinos pagalbos priemonių įrašymo į

kompensavimo sąrašus ir jų keitimo tvarkos aprašu, patvirtintu Lietuvos Respublikos sveikatos

apsaugos ministro 2002 m. balandžio 5 d. įsakymu Nr. 159 „Dėl Ligų, vaistinių preparatų ir medicinos

pagalbos priemonių įrašymo į kompensavimo sąrašus ir jų keitimo tvarkos aprašo patvirtinimo“, buvo

įvertinta šios sveikatos technologijos – vakuuminės krūties biopsijos – kaip medicinos pagalbos

priemonės (MPP), funkcinė vertė. Vakuuminės krūties biopsijos funkcinė vertė buvo vertinta krūties

vėžio atveju (1 lentelė).

1 lentelė. Vakuuminės krūties biopsijos funkcinė vertė.

Funkcinės vertės

kriterijai

Vakuuminė krūties

biopsija Pastabos

Ligos įtaka sveikatai 3 Krūties vėžys laikomos gyvybei pavojinga

būkle.

Socialinė MPP svarba 2

Vakuuminė krūties biopsija gali padėti

užkirsti kelią gręsiančiam neįgalumui ir

prarastam darbingumui, jei naudojama laiku.

MPP inovatyvumas 1

Vakuuminė krūties biopsija gali iš dalies

pakeisti alternatyvias MPP, kai nepavyksta

nustatyti diagnozės, tačiau lieka įtarimas dėl

krūties darinio piktybiškumo.

MPP klinikinis

efektyvumas 3

Vakuuminės krūties biopsijos efektyvumas

didesnis nei alternatyvių MPP; naudojama

tada, kai alternatyvios MPP neefektyvios arba

yra indikacijų, dėl kurių alternatyvios MPP

nėra efektyvios.

MPP ekonominis

efektyvumas 2*

Vakuuminės krūties biopsijos klinikinis

efektyvumas didesnis nei alternatyvių MPP,

tačiau ir jos kaina yra aukštesnė.

Galutinis balas 11

*Ekonominio efektyvumo aspektas nebuvo vertintas, tačiau vakuuminės krūties biopsijos metu

naudojamų priemonių kaina yra didesnė negu stulpelinei biopsijai.

14

IŠVADOS

1. Krūties vėžys yra antra dažniausia moterų mirties dėl vėžio priežastis labiau išsivysčiusiuose

regionuose, tačiau dėl ankstyvo krūties vėžio nustatymo ir gydymo 5 m. išgyvenamumas siekia

~89%. Atrankinė mamografinė patikra dėl krūties vėžio, atliekama kas 2 metus, parodė

didžiausią mirtingumo mažinimo naudą 50–69 metų moterims. Jei po profilaktinio patikrinimo

yra įtarimų dėl vėžio, patologinė diagnostika turėtų remtis biopsijos rezultatais.

2. Rinkoje yra 4-ių gamintojų prietaisai, turintys CE ir FDA ženklus, skirti vakuuminei krūties

biopsijai: Mammotome®, EnCor®, ATEC®, VaCora®; šios sistemos turi keletą skirtingų

modelių. Visos sistemos gali būti naudojamos trimis būdais – rentgeno (mamografija),

ultragarso arba magnetinio rezonanso kontrolėje, tačiau tik naudojantis ultragarsiniu prietaisu

procedūra vyksta esamuoju laiku.

3. Dažniausios su VABB susijusios komplikacijos – intraoperacinis kraujavimas (0.5–21.3%) ir

hematomos (0.1–41.3%). Bendras visų nepageidaujamų atvejų dažnis – 0–41.3%, tačiau

dauguma šių komplikacijų – nekeliančios pavojaus. Biopsinės adatos diametras gali daryti įtaką

komplikacijų dažniui, tačiau norint tai patvirtinti, reikalingi papildomi tyrimai.

4. Visuose tyrimuose klaidingai teigiamų atvejų dažnis lygus 0% – VABB pašalina daug įtariamai

navikinio audinio ir po VABB atliekant chirurginę biopsiją gaunami priešingi rezultatai (be

vėžinių ląstelių). Klaidingai neigiamų atvejų dažnis tyrimuose varijavo nuo 0% iki 23.2%.

Pagal vaizdinimo sistemas, didžiausias klaidingai neigiamų atvejų dažnis buvo su MRI-VABB

– 6–23.2%. Klaidingi diagnostinių tyrimų rezultatai sukelia problemų, dėl kurių pacientui gali

būti nesuteiktas savalaikis gydymas.

5. Bendras VABB jautrumas siekia 88.9–98.4%, specifiškumas – 100%. Bendras krūties vėžio

neįvertinimo rodiklis svyravo apie 0–23.2% (nuo 0 iki 114 pacientų klasifikuoti kaip

nesergantys krūties vėžiu (pagal TLK-10-AM: C50 arba D05)). Pagal vaizdinimo sistemas, S-

VABB rodikliai (jautrumas: 89.2–94.7%, krūties vėžio neįvertinimas: 10.9% (155 iš 1419

pacientų)) geresni nei MRI-VABB (jautrumas: 0%, krūties vėžio neįvertinimas: 15.2% (56 iš

368 pacientų)). Biopsinės adatos diametras testo tikslumui reikšmingos įtakos neturėjo.

6. Daugelis pacientų (97.3%) buvo patenkinti kosmetiniais rezultatais po VABB, ir, prireikus, vėl

rinktųsi VABB procedūrą (88–92.3%), o ne chirurginę biopsiją. Vis dėlto, gyvenimo kokybės

ir bendro pasitenkinimo procedūra balai buvo mažesni jaunesnio amžiaus moterų grupėse

(p=0.02), taip pat, pacientai, kuriems diagnozuotas piktybinis krūties navikas, statistiškai

reikšmingai blogiau vertino VABB procedūrą (p=0.011–0.035).

https://www.google.lt/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&cad=rja&uact=8&ved=0ahUKEwinmPqYw8rOAhXDVBQKHYBUDSEQFggqMAE&url=http%3A%2F%2Fwww.bardbiopsy.com%2Fproducts%2Fencor.php&usg=AFQjCNFmTa_OdlfrzsW94zav-WxUmiybPw&bvm=bv.129759880,d.d24

https://www.google.lt/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&cad=rja&uact=8&ved=0ahUKEwiEnoHFwsrOAhVB7xQKHWBeCvEQFggjMAE&url=http%3A%2F%2Fwww.bardbiopsy.com%2Fproducts%2Fvacora_video.php%3Fi%3Dmri&usg=AFQjCNHVMMS8BhRQwh5No8Jz0sL1m8AB-Q

15

REKOMENDACIJOS

1. Atsižvelgiant į didesnę VABB kainą, lyginant su rutiniškai atliekamomis biopsijomis (CNB),

VABB turėtų būti skiriama pacientams, kuriems įprastais diagnostiniais metodais nepavyko

nustatyti diagnozės, tačiau specialistams išliko abejonė dėl darinio piktybiškumo.

2. Šiuo metu turimų diagnostinio tikslumo rezultatų patikslinimui ir patvirtinimui reikalingi

palyginamieji prospektyviniai tyrimai, kuriuose VABB saugumo bei efektyvumo rezultatai

būtų sugretinami su alternatyvių technologijų (CNB, FNA) ar kitų VABB sistemų rezultatais.

16

SUMMARY

Methodology of Health Technology Assessment

The assessment was made on the basis of health technology assessment methodology

prepared by International European Health Technology Assessment Network ‘EUnetHTA’. The rapid

assessment was based primarily on a basic systematic literature search in the following sources:

• Cochrane Library database;

• PubMed (Medline);

• CRD database;

• Hand searches including articles from the manufacturers.

The systematic literature search was conducted with time limitation from 2012; systematic

literature search strategies are introduced further in Appendix 2.

Relevant articles for the ‘Safety’ and ‘Clinical effectiveness’ domains were selected by the

Chief specialists of Medical Technology division of VASPVT (State Health Care Accreditation

Agency under the Ministry of Health, Lithuania). Search filter for studies of diagnostic tests was not

used to increase search sensitivity. Also, systematic reviews on the topic were searched and their lists

of included studies were used to validate search strategy and to make sure all relevant studies were

identified. References were included or excluded according to the PICO-scheme described in the

summary.

In terms of study design, no HTAs or RCTs were found; only prospective and retrospective

case series were selected for answering questions related to the domains ‘Safety’ and ‘Clinical

effectiveness’. For the two other domains ‘Health problem and current use of the technology’ and

‘Description and technical characteristics’, no restrictions in terms of study design were applied.

In cases where questions within the domains ‘Health problem and current use of technology’

and ‘Description and technical characteristics of technology’ could not be answered using the

information retrieved from the basic systematic literature search described earlier, additional searches

within specific information sources (e.g. databases for clinical guidelines, websites of manufactures

etc.) and, if needed, hand searching were performed.

The quality of diagnostic accuracy studies was assessed by QUADAS-2 checklist (see

Appendix 5). The tool assesses study quality in four domains: patient selection, index test, reference

standard, and flow and timing. Each domain is assessed in terms of risk of bias, and concerns

regarding applicability (for the first three domains). Application of the tool results in a judgement of

risk of bias for each study categorised as low, high, or unclear. For assessing the quality of systematic

review, the AMSTAR checklist for systematic reviews was used (see Appendix 5). Also, the quality of

3 CSs (one for ‚Safety domain‘ (adverse events) and two for ‚Clinical effectiveness‘ domain (quality

of life)) was assessed using the IHE checklist for case series (see Appendix 5).

Study details, study population, results regarding efficacy/ effectiveness and safety of selected studies

were extracted into a data extraction tables (see Appendix 4).

17

PICO for Vacuum–assisted breast biopsy system

Population Women all ages with suspected:

• high-risk/ malignant breast lesions (B3–B5);

• calcifications (B2);

• lesions only seen on MRI.

MeSH: Breast Neoplasms (C04.588.180, C17.800.090.500).

Intervention Vacuum–assisted breast biopsy (VABB) under ultrasound (US-VABB) or

stereotactic (S-VABB) or magnetic resonance imaging (MRI-VABB)

guidance.

MeSH terms: Biopsy (E01.370.225.500.384.100, E01.370.225.998.054, E01.370.388.100, E04.074,

E05.200.500.384.100, E05.200.998.054, E05.242.384.100); Image-Guided Biopsy

(E01.370.225.500.384.100.370, E01.370.225.998.054.370, E01.370.388.100.370, E04.074.370,

E05.200.500.384.100.370, E05.200.998.054.370, E05.242.384.100.370); Mammary Ultrasonography

(E01.370.350.850.860, E01.370.378.850); Interventional Ultrasonography (E01.370.350.850.855,

E04.502.890); X-Ray Tomography (E01.370.350.700.810, E01.370.350.825.810); Magnetic

Resonance Imaging (E01.370.350.825.500).

Comparison • Histology/ Surgical pathology;

• Core needle biopsy (CNB);

• Fine needle aspiration cytology (FNAC).

MeSH terms: Surgical Pathology (H02.403.650.510); Biopsy (E01.370.225.500.384.100,

E01.370.225.998.054, E01.370.388.100, E04.074, E05.200.500.384.100, E05.200.998.054,

E05.242.384.100); Image-Guided Biopsy (E01.370.225.500.384.100.370, E01.370.225.998.054.370,

E01.370.388.100.370, E04.074.370, E05.200.500.384.100.370, E05.200.998.054.370,

E05.242.384.100.370); Needle Biopsy (E01.370.225.500.384.100.119, E01.370.225.998.054.119,

E01.370.388.100.100, E04.074.119, E04.665.100, E05.200.500.384.100.119, E05.200.998.054.119,

E05.242.384.100.119); Fine Needle Biopsy (E01.370.225.500.384.100.119.500,

E01.370.225.998.054.119.500, E01.370.388.100.100.500, E04.074.119.500, E04.665.100.500,

E05.200.500.384.100.119.500, E05.200.998.054.119.500, E05.242.384.100.119.500).

Outcomes

Efficacy

1) Diagnostic accuracy (Specificity, Sensitivity);

2) Disease specific-mortality, Disease specific-morbidity;

3) QoL and satisfaction.

Safety

1) Adverse events (AE);

2) False negative/ false positive findings.

PICO research questions: Is VABB system for the diagnosis of high risk or malignant neoplasm

of breast, calcifications or lesions only seen on MRI, more effective and safer concerning

diagnostic accuracy, therapeutic impact, quality of life and adverse events than comparative

diagnostic procedures?

Target Condition

Breast cancer (BCa) starts when cells in the breast begin to grow out of control. These cells

usually form a tumor that can often be seen on an x-ray or felt as a lump. Benign breast tumors are

abnormal growths, but they do not spread outside of the breast and they are not life threatening, but

some benign breast lumps can increase a woman's risk of getting breast cancer. The tumor is malignant

(cancerous) if the cells can grow into (invade) surrounding tissues or spread (metastasize) to distant

areas of the body. According to the International Statistical Classification of Diseases and Related

Health Problems 10th Revision (ICD-10) breast cancers are defined as a Malignant neoplasm of breast

with code C50, a Carcinoma in situ of breast with code D05, and a Benign neoplasm of breast with

code D24. (A0002)

Main risk factors for developing breast cancer are: gender, older age, genetic predisposition

(usually genes BRCA1 and BRCA2), exposure to oestrogens (endogenous and exogenous), dense

18

breast tissue, certain benign breast conditions (usually atypical hyperplasia), ionising radiation,

alcohol, physical inactivity, overweight or obesity. (A0003)

Breast cancer typically produces no symptoms when the tumor is small and most easily

treated. Therefore, it is very important for women to follow recommended screening guidelines for

detecting breast cancer at an early stage. Less common signs and symptoms include breast pain or

heaviness; persistent changes to the breast, such as swelling, thickening, or redness of the breast’s skin;

and nipple abnormalities such as spontaneous discharge (especially if bloody), erosion, or retraction. It

is important to note that pain (or lack thereof) does not indicate the presence or the absence of breast

cancer. (A0004; A0005)

According to the IHME (Institute of Health Metrics and Evaluation) data in 195 countries (in

2015) global breast cancer DALYs in all ages were 15.1 million years. The total average direct cost of

BCa amounted per patient in Lithuania was about 2580 € in 2011. The BCa direct medical cost

increased according to the diagnosed stage of diseases from 2409 € in stage 1 to 3688 € in stage 4.

(A0006)

Target Population

Rates of breast cancer are low in women under 40 – breast cancer mainly affects women over

50 and the risk increases with age: rates begin to increase after age 40 and are highest in women over

age 70. (A0007)

In 2012 (the latest year for which information is available) breast cancer was the second of the

most common diagnosed cancers worldwide (for both sexes): 12% of all cancers diagnosed (1.7

million people), and the fifth the most common causes of cancer death worldwide (for both sexes): 6%

of all cancer deaths; (522,000 people). Among females breast cancer was the most common cause of

cancer death in less developed regions (324,000 deaths, 14.3% of total), and it is now the second cause

of cancer death in more developed regions (198,000 deaths, 15.4%) after lung cancer. Despite the high

incidence rates, in Western countries, 89% of women diagnosed with BCa are still alive 5 years after

their diagnosis, which is due to detection and treatment. (A0023)

Also, breast cancer is the most common cancer in Lithuanian women, about 2,500 women are

newly diagnosed with BCa and approximately 550 deaths occur from this disease annualy. In 2015

BCa (according to the ICD-10: C50) morbidity was 12,377 cases (7.9 cases per 1000 women) and

there were 576 death cases in 2015. Information about benign breast lumps is uncertain because of a

variety of diagnoses are merged in statistical forms. (A0023)

Utilisation of the VABB Technology

Vacuum-assisted breast biopsy is a tissue sampling technique that uses a special instrument

and imaging guidance to remove samples of breast tissue through a single, small skin incision. This

technique allows the surgeon to remove more tissue through a single incision than is possible with a

traditional core biopsy and is a much less invasive procedure than an open surgical biopsy. However,

not all breast abnormalities can be sampled using the VABB, since some conditions of the breast may

make the areas of interest difficult to locate using imaging techniques. (A0001; F0001)

The global breast biopsy (all types and all locations) market is poised to reach $728.8 million

(around 683.3 million €) by 2020 from $436.4 million (around 409.2 million €) in 2015. According to

the subbmission file, the price of the VABB technology (EnCor®) in Lithuania is around 91,000 €;

additionally, direct and indirect costs is about 67,000 €. However, an ATEC® Sapphire console, which

may be used for all modalities, costs £15,000 (around 17,000 €). (A0011)

Current Management of the Condition

The diagnosis of breast cancer is based on clinical examination in combination with imaging,

and confirmed by pathological assessment. Pathological diagnosis should be based on a core needle

19

biopsy, obtained preferably by ultrasound or stereotactic guidance. A marker (e.g., surgical clip)

should be placed into the tumour at biopsy, to ensure surgical resection of the correct site. Final

pathological diagnosis should be made according to the World Health Organization (WHO)

classification and the tumour–node–metastases (TNM) staging system. Other assessments include:

complete personal medical history, family history relating to breast/ ovarian and other cancers,

physical examination, a full blood count, liver and renal function tests, alkaline phosphatase and

calcium levels. (A0024)

Eighteen European countries have established national or regional population-based

mammography screening programmes, to detect breast cancers at a pre-clinical stage. The European

Guidelines for quality assurance in BCa screening and diagnosis recommend performance parameters

and indicators that should be monitored in any screening programme. Mammography screening, every

2 years, has shown the greatest mortality reduction benefit in the age group of 50–69 years and is

recommended by the European Union and numerous individual countries. (A0025)

Regulatory Status

The most commonly used vacuum-assisted biopsy devices in clinical settings are VaCora®

(CR Bard, Inc., Covington, GA, USA), EnCor® (EnCor® MR, SenoRx, Allso Viejo, CA, USA),

Mammotome® (Ethicon Endo-surgery, Inc., Cincinnati, Ohio, USA) and ATEC® (Suros Surgical

Systems, Inc., Indianapolis, USA). Also, there are some new products as Bexcore® (Medical Park Co.,

Ltd., Korea) that already have a CE mark (in 2015) and FDA approval is in progress; however, data

about this product is limited. (A0022)

The Mammotome® minimally invasive biopsy system was approved for clinical application

by the FDA in April 1995. The summaries of safety and effectiveness were presented to the FDA in

2001 (Mammotome®), in 2004 (ATEC®), in 2008 (VaCora®), and in 2011 (EnCor®). Recently, the

FDA approved use of the VABB devices for the therapeutic purpose of benign lesions. (A0020)

In 2006, VaCora® VABB system received CE Mark clearance in Europe, followed by a

controlled European rollout in October 2006. Also, launching VABB system in November 2005,

EnCor® has received approval to apply the CE Mark in 2008. ATEC® breast biopsy system is CE

marked since January 2009. The CE mark covers the console (ATEC® Sapphire) and disposable

handpiece. (A0020)

The VABB technology is fully or partly reimbursed in some countries; however,

reimbursement is inadequate. Needles for VABB in National Cancer institute (Lithuania) are available

mostly through sponsors, only a part of such procedures are reimbursed through National Health

Insurance Fund. (A0021)

Features of the technology

Vacuum-assisted breast biopsy (VABB), allowing for multiple and larger coaxial core

sampling at 360° with a single skin insertion, has been introduced onto the market in the mid-1990s.

The first VABB biopsy (Mammotome® Breast Biopsy System) was performed on August 5, 1995 in

Denver, USA; since 1996, the technology has been used in Europe. Currently, there are four systems in

routine use using 7 to 14 French gauge (G) needles or probes: Mammotome®, VaCora®, EnCor® and

ATEC®; these systems also have few models and versions. All VABB systems can be used with

stereotactic (S), ultrasound (US) or magnetic resonance (MRI) guidance. Only during US-VABB real-

time visualisation is available. (B0001; B0003)

In general, VABB is a minimally invasive intervention and is superior to open biopsy in

regards to cosmetic outcome, the duration of the procedure, and postoperative internal scars. The

procedure usually takes <1 hour and the patient may be discharged from the hospital immediately. This

represents a significant time and cost savings compared to open biopsy (duration 1–2 hours, few hours

of recovery time). The samples acquired using VABB are much larger than samples acquired using

core needle biopsy (CNB) and CNB requires 4 to 6 biopsy needle insertions, therefore, VABB only 1,

20

because tissue samples can be obtained with a single insertion. In the event of bleeding complications,

there is a possibility of direct aspiration of blood during VABB. Also, VABB sometimes could be used

to remove benign breast lesions such as fibroadenomas. (B0002; B0001)

The healthcare setting in which VABB is used depends on the imaging technique (MRI,

ultrasound or stereotactic). Both stereotactic- and ultrasound-image-guided biopsies can be done in an

outpatient setting by a radiologist or advanced practitioner. MRI-guided biopsies will be done in a

radiology department by a radiologist or advanced practitioner. (B0004)

Investments and tools required to use the technology

Vacuum effect is achieved by the use of a free-standing vacuum console (except VaCora®)

(which remains outside the MRI suite during MRI-VABB). Depending on VABB device, 3 imaging

modalities (US, S, MRI) need 1 (ATEC®), 2 (EnCor®) or 3 (Mammotome®) different consoles for

the procedure. Console is connected to the biopsy probe (or handpiece) by plastic tubing and needle

also is mounted to a probe. Probes with needles and side collection chambers, tubing sets and debris

canisters are all disposable components. Dedicated prone tables and upright systems for biopsies are

required. Some more disposable items are required for every procedure: marker clip, surgical scalpel,

sterile gloves, compreses, drapes, little pot with a solution of 10 % formaldehyde to fixate the tissue/

specimen, few syringes with needles to administer the anaesthetics, some sterile ultrasound gel (for

US-VABB). (B0009)

According to Interdisciplinary Consensus Recommendations for the use of Vacuum-Assisted

Breast Biopsy under Sonographic Guidance (German Society of Senology) attending a special VABB

course is recommended and the first 10 examinations should be conducted under the supervision of an

investigator with experience performing VABB. With MRI, the initial training involves 20 procedures

according to the European guidelines and then a minimum of 25 procedures per year to maintain

competence. (B0013)

Features of the comparator and the reference Standard

Since 1968, fine needle aspiration (FNA) has long been the most functional examination to

determine the nature of the nodules, but gradually, in view of limitations, core needle biopsy (CNB)

was introduced; the main advantage of CNB is that it enables histologic diagnosis. As a single sample

is obtained each time the device is inserted, multiple insertions are needed to obtain sufficient breast

tissue, usually, 4 to 6 samples are taken. CNB is an outpatient procedure, minimally invasive, well

tolerated and quick. (B0003; B0001; B0004)

Historically, surgical excision was the “gold standard” or „reference standard“ for the

diagnosis of BCa. In contemporary practice, other biopsy methods (guided by imaging modalities) has

largely, but not completely, replaced surgical excision. Diagnostic excision biopsy is now relatively

unusual and are carried out specifically for the purpose of establishing a diagnosis in patients with

inconclusive needle biopsy results. During a procedure, first, a wire is positioned in the abnormal

breast tissue to identify the area to be cut out. Then, general anesthesia or a local anesthesia with

sedation is used. A surgeon makes an incision in the breast, removes the localization wire and a large

section of tissue, typically about the size of a golf ball. The incision in the breast is then closed with

stitches and covered with a protective bandage. (B0001; B0004)

Patient safety

Adverse events related to diagnostic VABB technology were reported in 7 case series

(n=2697); they were divided into 3 groups: device and/ or procedure related, serious and non-serious

adverse events. (C0008; C0004)

Intraoperative bleeding which was reported in 3 case series was an only device and/ or

procedure related adverse event; the incidence rate varied from 0.5% to 21.3%. Although a high rate

21

was reported, most of cases were classified as small bleeding – 17.4%. Infection, haematoma with

surgical intervention or moderate/ severe haematoma and moderate/ severe scar formation were titled

as serious adverse events and reported in 3 case series; the incidence rate of these complications varied

from 0% to 6.2%. Non-serious adverse events – skin ecchymosis, small haematoma, small scar

formation – were reported in 6 case series; the incidence rate varied from 1.1% to 41.3%. (C0008;

C0004)

1 case serie compared VABB systems (Mammotome® and ATEC®) with different needle

diameters (8G, 9G, 11G, 12G) regarding intraoperative bleeding, haematoma and scar formation in

178 cases of S-VABBs. Results showed more interventional bleedings (p<0.001) and post-

interventional haematomas (p=0.029) with the larger needle sizes significantly for Mammotome®

(11G vs. 8G) and not significantly for ATEC® (12G vs. 9G). Also, 11G Mammotome® system

revealed significantly less bleedings (p=0.015)/ haematomas (p=0.001) compared to the ATEC® 12G

system while there were no significant differences for the large systems. No significant correlation was

found between scar formation, VABB system or needle size. (C0004)

1 included case serie had the alternative technology – CNB, however, adverse events were not

provided and not analysed; none of the included case series reported adverse events related to

reference standard. (C0008)

The most common complications of VABB are haematomas and bleeding. To minimize the

risk of bleeding, patients on anticoagulation therapy need to have their treatment stopped or adjusted.

Also, immediately after the biopsy needle is withdrawn from the breast, compression of the biopsy site

is performed to achieve hemostasis. (C0007; C0062)

False positive/ negative findings were reported in 16 case series (of 19). False positive (FP)

rate equalled 0% in all included studies. It can be explained because occasionally VABB removes the

entire target lesion that is being biopsied, rendering subsequent surgical biopsies unable to confirm the

findings of the index test procedure. In such cases of VABB diagnoses of malignancy, it is considered

that VABB results are true positive instead of FP as malignancy was completely removed at biopsy.

FN values ranged from 0% to 23.2% in all included studies. (C0006)

According to specific imaging modality FN rate were: US-VABB FN rate after surgical

excision in 1 study was equal 1.3% (2/ 152 pts.), S-VABB FN rate in 5 studies varied from 0% to

19.4% (114/ 589 pts.) and MRI-VABB FN rate in 4 studies varied from 6% (4/ 67 pts.) to 23.2% (16/

69 pts.). In comparison with CNB, CNB had higher FN rate than VABB – 42.1% (8/ 19 pts.) vs. 9.1%

(1/ 11 pts.). (C0006)

Misinterpretation of tests, based on FP and FN findings, may lead to over- or undertreating

patients. While FP results may cause worry, anxiety, distress and perceptions of BCa risk even several

years later, physical issues related to diagnostic procedures and economic costs, a FN finding can give

a false sense of security even though the cancer is present as well as delay treatment. (C0006)

Test accuracy

The test accuracy is based upon a one-sided comparison between the results of the index test

and those of the reference standard (surgical excision). It is believed that surgical excision is 100%

reliable, still it is important to note that the assumption of 100% accuracy for the reference standard

rarely holds true in practice. (D1003)

Overall sensitivity varied from 0% to 100%. Seven case series reported sensitivity equal to

0% and three case series equal to 100%. Also, six studies valued VABB sensitivity from 88.9% to

98.4%. Overall specificity was reported in all sixteen included studies and was 100%. Positive/

negative predictive values (PPV/ NPV) were reported in all 16 studies; PPV ranged from 0% to 100%,

and NPV ranged from 75.7% to 100%. Overall underestimation rate varied from 0% to 23.2% (from 0

to 114 patients were incorrectly classified as not having a BCa) in sixteen studies. However,

underestimation rate mostly varied from 0% to 7.6% (from 0 to 16 patients incorrectly classified as not

having a BCa). (D0020; D0029; D1001; D1006; D1019)

22

VABB was guided with three different imaging modalities (ultrasound, stereotactic or

magnetic resonance) in 15 included studies. Sensitivity varied from 0% to 100% in all imaging

modalities; however, S-VABB sensitivity mostly varied from 89.2% to 94.7%, MRI-VABB mostly

was equal to 0%, and US-VABB sensitivity was 98.4%. All imaging modalities had specificity value

of 100%. PPV in all imaging modalities ranged from 0% to 100%, however 4/5 studies stated that S-

VABB value is 100% and 3/4 studies stated that MRI-VABB value is 0%. NPV of S-VABB ranged

from 80.6% to 100%, NPV of MRI-VABB ranged from 76.8% to 94%, and NPV of US-VABB was

reported as 93.3%. Underestimation rates according to imaging modalities were: US-VABB – 1.3% (2

of 152 patients were incorrectly diagnosed as not having a BCa), S-VABB – 10.9% (155 of 1419

patients), and MRI-VABB – 15.2% (56 of 368 patients). (D1006; D1007; D1019)

VABB was performed using different needle available in a wide variety of outer diameters

described by gauge numbers (7G, 8G, 9G – large core, and 10G, 11G, 12G, 13G – small core).

Sensitivity in a large core group varied from 0% to 91.5%; however, sensitivity in this group mostly

was 88.9–91.5%. Sensitivity in a small core diameter group varied from 0% to 100%; however,

sensitivity in this group mostly was 89.2–98.4%. Specificity according to the needle diameter in both

groups was 100%. PPV in both groups ranged from 0% to 100%. Meanwhile NPV in the large core

group was 75.7–94%, while NPV in the small core group was 80.6–100% (in most cases NPV was

80.6–93.3%). Underestimation rates according to needle sizes were: large core – 9.1% (76 of 834

patients were incorrectly diagnosed as not having a BCa), and small core – 10.6% (148 of 1400

patients). (D1006; D1007; D1019)

One retrospective case serie had alternative for VABB – core needle biopsy with 14G needle;

patients after VABB procedures or CNB procedures had the same reference standard (surgical

excision). All in all, patients were classified into two groups, where 11 patients received VABB and

subsequent surgical procedure (9 of 11 also underwent CNB), and 19 patients who underwent CNB

and subsequent surgical procedure (9 of 19 also underwent VABB and were dublicated). The

probabilities that a test will indicate 'disease' among those with the disease (sensitivity) were 83.3%

(VABB) and 0% (CNB), and the fraction of those without disease who will have a negative test result

(specificity) were 100% for both tests. However, the percentages of patients with a positive test who

actually have the disease (PPV) were 100% and 0%, respectively; the percentages of patients with a

negative test who do not have the disease (NPV) were 83.3% and 57.9%, respectively. In this case

underestimation rates were quite different: 9.1% (1 of 11 patients) for the VABB and 42.1% (8 of 19

patients) for the CNB. (D0020; D1002)

Health-related quality of life and patient satisfaction

Two studies reported quality of life (QoL) and patient safisfaction outcomes. In one

prospective study of 90 women included biopsy experience was described with a validated instrument

for assessing short-term QoL related to diagnostic testing. In this case, digital breast tomosynthesis

guided VABBs (S-VABB (DBT)) were less tolerated (worst biopsy experience in terms of pain or

discomfort, fear or anxiety, and regarding physical and mental function after testing) than digital

mammography guided VABB (S-VABB (MMx)) ones. Same study also included questions about the

patient’s satisfaction, such as “the staff showed concern for my worries” and “the doctor explained

what to expect during the biopsy”. However, overall satisfaction and the level of embarrassment

during testing resulted similar for both procedures. (D0012; D0017)

Another retrospective study, which reported patient satisfaction, included 189 patients, of

which 150 patients received 9 gauge needle VABB while using ATEC® biopsy device and 39 patients

received 11 gauge needle VABB using Mammotome® system. Comparing the two biopsy devices no

significant difference was found between the two devices regarding the patient condition while

undergoing (p=0.25) and after (p=0.2) the biopsy. However, the ATEC® system was significantly

more frequently associated with self-reported complications (p=0.005; 41.3% and 17.9%) and 43.5%

patients of all self-reported complications (n=69) reported severe pain. In both groups (ATEC® and

Mammotome®) patients were mostly satisfied with the cosmetic result after the biopsy (97.3% and

23

97.4%, respectively) and would again prefer VABB to an open surgical biopsy (88% and 92.3%,

respectively). (D0012; D0017; D0029)

However, in both studies scores were lower in the youngest age group, with short-term QOL

decreasing as long as the decrease in patient age. Also, older women evaluated the procedure as less

consciousness-affecting (condition during the procedure) than younger (p=0.02), and therefore the

younger group announces a higher frequency (p=0.02) of complications. Moreover, patients diagnosed

with a malignant lesion rated the VABB statistically significantly worse in terms of condition during/

after the procedure and in evaluation of the cosmetic result after the biopsy (p=0.011; p=0.035;

p=0.024, respectively) than those with a benign histology. (D0012; D0017; D0029)

24

HEALTH PROBLEM AND CURRENT USE OF THE VABB

Target Condition

Breast cancer (BCa) starts when cells in the breast begin to grow out of control. These cells

usually form a tumor that can often be seen on an x-ray or felt as a lump. Benign breast tumors are

abnormal growths, but they do not spread outside of the breast and they are not life threatening, but

some benign breast lumps can increase a woman's risk of getting breast cancer. The tumor is malignant

(cancerous) if the cells can grow into (invade) surrounding tissues or spread (metastasize) to distant

areas of the body [1,2]. According to the International Statistical Classification of Diseases and

Related Health Problems 10th Revision (Australian Modification) (ICD-10) breast cancers are defined

as a Malignant neoplasm of breast with code C50, a Carcinoma in situ of breast with code D05, and a

Benign neoplasm of breast with code D24 [3].

Breast cancers can start from different parts of the breast. Most breast cancers begin in the

ducts that carry milk to the nipple (ductal cancers), some start in the glands that make breast milk

(lobular cancers). A small number of cancers start in other tissues in the breast; these cancers are called

sarcomas and lymphomas and are not really thought of as breast cancers [1]. Also, most breast lumps

are not cancer, they are benign; any breast lump or change needs to be checked by a health care

specialist to determine whether it is benign or malignant, and whether it might impact your future

cancer risk [1].

Ductal carcinoma in situ (DCIS) is the most common type of non-invasive breast cancer.

DCIS is called "non-invasive" because it has not spread beyond the milk duct into any normal

surrounding breast tissue. DCIS is not life-threatening, but having DCIS can increase the risk of

developing an invasive breast cancer later on and it does require treatment to prevent the condition

from becoming infiltrating (ICa). Most recurrences happen within the 5 to 10 years after initial

diagnosis; the chances of a recurrence are under 30% [4,5].

Most breast cancers are invasive, or infiltrating. These cancers have broken through the walls

of the glands or ducts where they originated and grown into surrounding breast tissue. The prognosis

of invasive breast cancer (invasive lobular carcinoma (ILC), invasive ductal carcinoma (IDC)) is

strongly influenced by the stage of the disease [2]. About 8 of 10 invasive breast cancers are IDCs and

about 1 invasive breast cancer in 10 is an ILC [6].

Main risk factors for developing breast cancer are: gender, older age, genetic predisposition

(usually genes BRCA1 and BRCA2), exposure to oestrogens (endogenous and exogenous), dense

breast tissue, certain benign breast conditions (usually atypical hyperplasia), ionising radiation,

alcohol, physical inactivity, overweight or obesity [7].

Breast cancer typically produces no symptoms when the tumor is small and most easily

treated. Therefore, it is very important for women to follow recommended screening guidelines for

detecting breast cancer at an early stage. When breast cancer has grown to a size that can be felt, the

most common physical sign is a painless lump. Sometimes breast cancer can spread to underarm

lymph nodes and cause a lump or swelling, even before the original breast tumor is large enough to be

felt. Less common signs and symptoms include breast pain or heaviness; persistent changes to the

breast, such as swelling, thickening, or redness of the breast’s skin; and nipple abnormalities such as

spontaneous discharge (especially if bloody), erosion, or retraction. It is important to note that pain (or

lack thereof) does not indicate the presence or the absence of breast cancer. Any persistent change in

the breast should be evaluated by a physician as soon as possible [2].

According to the IHME (Institute of Health Metrics and Evaluation) data in 195 countries (in

2015) global breast cancer DALYs in all ages were 15.1 million years [8]. The total average direct cost

of BCa amounted per patient in Lithuania was about 2580 € in 2011. The BCa direct medical cost

increased according to the diagnosed stage of diseases from 2409 € in stage 1 to 3688 € in stage 4 [9].

25

Target Population

Rates of breast cancer are low in women under 40 – breast cancer mainly affects women over

50 and the risk increases with age: rates begin to increase after age 40 and are highest in women over

age 70 [10,11].

In 2012 (the latest year for which information is available) breast cancer was the second of the

most common diagnosed cancers worldwide (for both sexes): 12% of all cancers diagnosed (1.7

million people), and the fifth the most common causes of cancer death worldwide (for both sexes): 6%

of all cancer deaths; (522,000 people). Among females breast cancer was the most common cause of

cancer death in less developed regions (324,000 deaths, 14.3% of total), and it is now the second cause

of cancer death in more developed regions (198,000 deaths, 15.4%) after lung cancer [12,13]. Also,

breast cancer is the most common cancer in Lithuanian women, about 2,500 women are newly

diagnosed with BCa and approximately 550 deaths occur from this disease annualy [14]. In 2015 BCa

(according to the ICD-10: C50) morbidity was 12,377 cases (7.9 cases per 1000 women) [15] and there

were 576 death cases in 2015 [16]. Information about benign breast lumps is uncertain because of a

variety of diagnoses are merged in statistical forms.

Utilisation of the VABB Technology

Vacuum-assisted breast biopsy (VABB) is a tissue sampling technique that uses a special

instrument and imaging guidance to remove samples of breast tissue through a single, small skin

incision. This technique allows the surgeon to remove more tissue through a single incision than is

possible with a traditional core biopsy and is a much less invasive procedure than an open surgical

biopsy [17]. However, not all breast abnormalities can be sampled using the VABB, since some

conditions of the breast may make the areas of interest difficult to locate using imaging techniques

[18]. Overall, vacuum-assisted biopsy is becoming more common, but it is still a relatively new

procedure for now, VABB could partially replace existing techniques in the near future [17]. The

global breast biopsy (all types and all locations) market is poised to reach $728.8 million (around

683.3 million €) by 2020 from $436.4 million (around 409.2 million €) in 2015 [19].

According to the subbmission file, the price of the VABB technology (EnCor®) in Lithuania

is around 91,000 €; additionally, direct and indirect costs is about 67,000 €. However, an ATEC®

Sapphire console, which may be used for all modalities, costs £15,000 (around 17,000 €) [20].

Current Management of the Condition

Eighteen European countries have established national or regional population-based

mammography screening programmes, to detect breast cancers at a pre-clinical stage. The European

Guidelines for quality assurance in BCa screening and diagnosis recommend performance parameters

and indicators that should be monitored in any screening programme. Mammography screening, every

2 years, has shown the greatest mortality reduction benefit in the age group of 50–69 years and is

recommended by the European Union and numerous individual countries [7].

It must be noted that the review stresses the importance of taking into account the risk of

over-diagnosis and over-treatment, as well as false positive (FP) screening, when balancing the

benefits and harms of screening. Screening programmes carry the risk of false negative (FN) results,

consequently a false feeling of security among patients and doctors may be instilled. Nevertheless,

mammography screening and population-based awareness programmes, together with improved

treatment, may contribute to mortality reduction in breast cancer. Therefore, there is recommended

(after a discussion of the benefits and risks with the woman who is to be screened) regular

mammography in women aged 50–69 years [7].

The diagnosis of breast cancer is based on clinical examination in combination with imaging,

and confirmed by pathological assessment. Clinical examination includes bimanual palpation of the

26

breasts and loco-regional lymph nodes and assessment for distant metastases (bones, liver and lungs; a

neurological examination is only required when symptoms are present). Imaging includes bilateral

mammography and ultrasound of the breast and regional lymph nodes [21]. An magnetic rezonance

imaging (MRI) of the breast is not routinely recommended, but should be considered in some cases.

Several new techniques are being tested for screening and diagnostic imaging, such as: 3D

mammography (breast tomosynthesis), 3D ultrasound, shear wave elastography and contrast-enhanced

mammography/ spectral mammography. None of these are routinely implemented as yet, but they have

the potential to increase diagnostic accuracy, especially in women with dense breasts [7].

Apart from imaging, pre-treatment disease evaluation includes pathological examination of

the primary tumour and cytology/ histology of the axillary nodes, if involvement is suspected. Other

assessments include: complete personal medical history, family history relating to breast/ ovarian and

other cancers, physical examination, a full blood count, liver and renal function tests, alkaline

phosphatase and calcium levels. Pathological diagnosis should be based on a core needle biopsy,

obtained preferably by ultrasound or stereotactic guidance [7,21]. A core needle biopsy (if this is not

possible, at least a fine needle aspiration indicating carcinoma) must be obtained before any type of

treatment is initiated. A marker (e.g., surgical clip, carbon) should be placed into the tumour at biopsy,

to ensure surgical resection of the correct site. As a minimum, ultrasound-guided fine needle aspiration

(US-FNA) or core needle biopsy (CNB) of suspicious lymph nodes should be carried out. Final

pathological diagnosis should be made according to the World Health Organization (WHO)

classification [22] and the tumour–node–metastases (TNM) staging system [7].

The choice of treatment strategy must be extensively discussed with the patient and take into

account the patient's preferences. It should be based on the tumour burden/ location (size and location

of primary tumour, number of lesions, extent of lymph node involvement) and biology (pathology,

including biomarkers and gene expression), as well as the age and general health status of the patient.

Management of breast cancer includes local treatment (surgery, breast-conservation surgery,

mastectomy, risk-reducing mastectomy, radiation therapy) and adjuvant systemic treatment (endocrine

therapy, chemotherapy, targeted therapy) [21]. All modalities (chemotherapy, endocrine therapy and

targeted therapy) used in adjuvant treatment may also be used preoperatively. Most patients who

present with unresectable non-metastatic disease will first be treated with primary systemic therapy. If

rendered resectable, this should be followed by surgery and radiation therapy, according to the

principles outlined for loco-regional advanced disease. In general, chemotherapy should not be used

concomitantly with endocrine therapy [7].

Regulatory Status

The most commonly used vacuum-assisted biopsy devices in clinical settings are VaCora®

(CR Bard, Inc., Covington, GA, USA), EnCor® (EnCor® MR, SenoRx, Allso Viejo, CA, USA),

Mammotome® (Ethicon Endo-surgery, Inc., Cincinnati, Ohio, USA) and ATEC® (Suros Surgical

Systems, Inc., Indianapolis, USA). Also, there are some new products as Bexcore® (Medical Park Co.,

Ltd., Korea) that already have a CE mark (in 2015) and FDA approval is in progress; however, data

about this product is limited [23].

The Mammotome® minimally invasive biopsy system was approved for clinical application

by the FDA in April 1995 [24]. The summaries of safety and effectiveness were presented to the FDA

in 2001 (Mammotome®), in 2004 (ATEC®), in 2008 (VaCora®), and in 2011 (EnCor®) [25].

Recently, the FDA approved use of the VABB devices for the therapeutic purpose of benign lesions

[17].

In 2006, VaCora® VABB system received CE Mark clearance in Europe, followed by a

controlled European rollout in October 2006 [26]. Also, launching VABB system in November 2005,

EnCor® has received approval to apply the CE Mark in 2008 [27]. ATEC® breast biopsy system is

CE marked since January 2009. The CE mark covers the console (ATEC® Sapphire) and disposable

handpiece [20].

27

The VABB technology is fully or partly reimbursed in some countries. However, in the view

of practitioners, reimbursement of VABB technology is inadequate in most countries [28]. In France, it

is considered important that practitioners and patients have access to this technique and be aware of its

availability [29]. Needles for VABB in National Cancer institute (Lithuania) are available mostly

through sponsors, only a part of such procedures are reimbursed through National Health Insurance

Fund.

Discussion

Breast cancer is the most common cancer in women both in the developed and less developed

world, and is increasing particularly in developing countries where the majority of cases are diagnosed

in late stages. Therefore, early detection in order to improve BCa outcome and survival remains the

cornerstone of breast cancer control [30]. It is visible that throughout the last two decades the interest

in early detection of BCa has increased steadily [30].

The diagnosis of BCa is based on clinical examination in combination with imaging, and

confirmed by pathological assessment. Minimally invasive breast biopsy has proved to be an important

technique in the diagnosis of BCa [31]. Where resources allow, vacuum-assisted biopsy techniques

might offer significant advantages for biopsy in a proportion of patients in achieving definitive pre-

operative diagnosis and reducing the need for surgical intervention [32].

Despite the high incidence rates, in Western countries, 89% of women diagnosed with BCa

are still alive 5 years after their diagnosis, which is due to detection and treatment [33]. However,

health statistics is mostly based on malignant cancer and information about benign breast lumps is

uncertain because a variety of diagnoses are merged in statistical forms. There is some concern that

over time some benign breast conditions could progress and become malignant, so they also should be

taken quite seriously and followed closely [34].

28

DESCRIPTION AND TECHNICAL CHARACTERISTICS OF THE

VABB TECHNOLOGY

Features of the VABB technology

Vacuum-assisted breast biopsy allowing for multiple and larger coaxial core sampling at 360°

with a single skin insertion, has been introduced onto the market in the mid-1990s with the goal of

eliminating the sampling difficulties associated with core needle biopsy. The first VABB biopsy

(Mammotome® Breast Biopsy System) was performed on August 5, 1995 in Denver, USA; since

1996, the technology has been used in Europe [35,36,37,38].

Currently, there are four systems in routine use based on the principle of single or multiple

cores using 7 to 14 French gauge (G) needles or probes: Mammotome®, VaCora®, EnCor® and

ATEC® [39]; these systems also have few models and versions. New products such as Bexcore® from

Korean manufacturer Medical Park Co., Ltd are also emerging, however, data about this technology is

limited [40,41].

Although the principles of operation are similar for all of these VABB systems, there are

some differences as well. The different systems are divided mainly into open or closed, depending on

whether the tissue sampling is performed manually or automatically. Only the EnCor® system has

fully automated and programmable needle functions and an oscillating scissor action instead of the

usual rotating cutter; the sharp Tri-Concave tip design used in the trochar and probe needle appears

particularly effective in penetrating dense parenchyma with minimal tissue shift (some users even

report that they no longer use a scalpel to nick the skin) [39,42,43]. The VaCora® system offers an

alternative concept to the three console-based vaccum systems, is the only battery-operated system and

thus the only true handheld system. The disadvantage of this system is that the device has to be

removed from the breast after each sample is taken; this causes more difficulty from blood and air and

it is essential to use a support for the gun in order to reduce the risk of displacing the cannula. The

vacuum aspirate is reported to be less powerful and the sampling process slower (69 vs. 39 minutes).

Coaxial systems (other three) are reported to be able to biopsy smaller lesions (10 vs. 19 mm), faster

and with greater confidence. However, this system is very compact, easy to handle and much less

costly. While the Mammotome® also takes individual samples, the biopsy system remains in the

breast during the entire intervention. The samples are transported to a chamber in the handle, where

they can later be removed [43,44,45].

All VABB systems can be used with stereotactic guidance (S) (either using upright devices or

prone table systems), ultrasound (US) or magnetic resonance (MRI) [42]. Only during US-VABB real-

time visualisation is available; it is equipped with computer software that facilitates easy automatic or

manual sample collection [38,46,47]. Table 1 shows a comparison of these systems.

Table 1. Comparison of VABB systems [39,43].

Attribute Mammotome® VaCora® ATEC® EnCor®

Drivers required Separate for US, S

and MRI Same for all Same for all Separate for MRI

Command unit

Same for all

Self-contained

Various options;

Requires different

units

Same for all

Vacuum

adjustment No No

Requires different

units Yes

Needle gauge 11 and 8 14 and 10 12 and 9 10 and 7

Multiple core

retrieval Yes No Yes Yes

Cutting method Rotating Rotating Rotating Scissor

29

Open or closed

tissue collection Open Open Closed Closed

Needle rotation Manual only Manual only Manual only Manual or

automated

Lavage No No Full Sample chamber

Biopsy site

marker system Yes No Yes Yes

Local anesthetic

function No delivery chanel

Allows deep local

delivery

Allows deep local

delivery

Allows deep local

delivery

The healthcare setting in which VABB is used depends on the imaging technique (MRI,

ultrasound or stereotactic). Both stereotactic- and ultrasound-image-guided biopsies can be done in an

outpatient setting by a radiologist or advanced practitioner. MRI-guided biopsies will be done in a

radiology department by a radiologist or advanced practitioner [20].

During a procedure with, the patient can be placed in prone, sitting, semireclining lateral or

upright position depending on an imaging modality used. A special table is necessary for prone

position, which is an extra cost and also takes more space [46]. Before VABB, imaging must be

performed on two planes, and the lesion metrics (length, width and depth) and site (side, clock

position, and distance from nipple to lesion) are to be documented on the image. During the entire

procedure the movement of the needle should be monitored on ultrasound [48].

If it is stereotactic biopsy, coordinates are calculated on the basis of +15° and -15° stereotactic

images/ projections; this allows calculation of the depth of the suspicious lesion. Then the lesion is

marked on the stereotactic views and computer calculates the correct biopsy position [46,49]. During

MRI-VABB a minimum of five scan series usually required: pre-contrast, post-contrast, confirm

obturator position, immediate post-biopsy scan and final scan after clip deployment [43].

After some initial images have been taken, the overlying skin will be cleansed with antiseptic.

A local anaesthetic will be injected into the skin and breast tissue. Repeat pictures or images are taken

at this stage to confirm the correct positioning of the biopsy site and needle. A small (3–4 mm)

incision is made in the anaesthetised skin and the needle inserted. When the radiologist is satisfied that

enough samples have been taken, a small titanium (strong, lightweight metal) marker clip (2 mm) may

be inserted into the breast via the biopsy needle. This is done so that the area of abnormality can be

located at a later date if surgery is required. If inserted, the clip is safe, cannot be felt, and does not

need to be removed [50,51].

Claimed benefit of the VABB in relation to the comparators [36,48,52,53,54,55]

• VABB is a minimally invasive intervention and is superior to open biopsy in regards to

cosmetic outcome, the duration of the procedure, and postoperative internal scars. The

procedure usually takes <1 hour and the patient may be discharged from the hospital

immediately. This represents a significant time and cost savings compared to open biopsy

(duration 1–2 hours, few hours of recovery time);

• The samples acquired using VABB are much larger than samples acquired using core needle

biopsy and CNB requires 4 to 6 biopsy needle insertions, therefore, VABB only 1, because

tissue samples can be obtained with a single insertion;

• VABB systems allow sampling around a full 360-degree arc either by manual rotation of the

driver or manual or automated rotation of the needle within the driver;

• In the event of bleeding complications, there is a possibility of direct aspiration of blood during

VABB;

• Image-guided vacuum-assisted core biopsy has been regularly used for gathering samples of

tissue in women with breast lesions suspicious of breast cancer, or when histological evidence

of a benign lesion is required. This procedure can also be used to remove benign breast lesions

such as fibroadenomas. This can reduce the need for open surgical biopsy or excision.

30

Features of the comparator and the reference standard

Comparators of the VABB technology

Fine needle aspiration. The publication of cytology results for a series of 2,111 FNA

samples by Franzen and Zajicek in 1968 established the technique as a vital part of the assessment of

breast lesions [56]. Currently, FNA is no longer the criterion standard for initial evaluation of all

palpable breast masses. However, it is particularly useful in the evaluation of cystic lesions detected by

ultrasonography [57].

Fine needle aspiration is a biopsy procedure that uses a thin needle on a syringe to draw fluid

and/or cellular material from a breast abnormality. The procedure can be done without using imaging

to guide the needle or under US or mammogram guidance. The technique of FNA is determined

largely by individual surgeon preference; a 21G needle attached to a 10 ml syringe is used most

commonly. To perform FNA, the skin should be disinfected with an alcohol wipe, and the needle is

passed through the lesion a number of times, while maintaining suction. Breast FNA is a quick test,

which takes 10 to 20 seconds for each sample. Once the biopsy is completed pressure is applied to the

puncture site to assist haemostasis. The aspirante is transfered to slides, which may be air-dried or

fixed according to the preference of the laboratory. Later, a cytologist examines the slides. The success

of FNA biopsy is highly dependent on the expertise of the cytologist, as well as on accurate

localization [57,58].

Fine needle aspiration is a quick way to distinguish between a fluid-filled cyst and a solid

mass and, possibly, to avoid a more invasive biopsy procedure. If, however, the mass is solid, a tissue

sample will be obtained [59].

Core needle biopsy. FNA has long been the most functional examination to determine the

nature of the nodules, but gradually, in view of limitations, CNB was introduced; the main advantage

of CNB is that it enables histologic diagnosis [57,60]. Nowadays, according to European Society of

Medical Oncology (ESMO) the diagnosis of BCa is based on clinical examination in combination with

imaging, and confirmed by pathological assessment. Pathological diagnosis should be based on a

CNB, when suspicious lesion is located by palpation (freehand biopsy) or obtained preferably by

imaging (stereotactic mammography, ultrasound, MRI). CNB (if this is not possible, at least a fine

needle aspiration indicating carcinoma) must be obtained before any type of treatment is initiated

[7,61].

CNB is a procedure that involves removing small samples of breast tissue through a hollow

core needle inserted through the skin. Basic CNB uses a special 11G, 14G, or 16G needle (the smaller

the gauge, the larger the diameter of the needle); all needles and syringes are for single use only. A

core needle, also called an automatic, spring-loaded needle, consists of an inner needle connected to a

trough, or shallow receptacle, covered by a sheath and attached to a spring-loaded mechanism [62].

The procedure is usually performed under local anesthesia and may take only 20 minutes; depending

on used imaging it may take up to an hour [61,63]. As a single sample is obtained each time the device

is inserted, multiple insertions are needed to obtain sufficient breast tissue, usually, 4 to 6 samples are

taken (4 to 6 insertions).The actual insertion of the needle is generally less than one minute. A small

marker may be placed at the biopsy site so that it can be located in the future if necessary. CNB is an

outpatient procedure, minimally invasive, well tolerated and quick [62,64,65].

Reference standard of the VABB technology

Surgical biopsy. Historically, surgical excision was the “gold standard” or „reference

standard“ for the diagnosis of palpable breast masses and, early in the era of mammographic screening,

for the diagnosis of suspicious nonpalpable lesions. In contemporary practice, CNB (guided by

imaging modalities) has largely, but not completely, replaced surgical excision [61,66]. Diagnostic

31

excision biopsy is now relatively unusual and are carried out specifically for the purpose of

establishing a diagnosis in patients with inconclusive needle biopsy results [67,68].

Open surgical biopsies often involve a two-step process. During procedure, intraoperative

ultrasound, specimen radiography, and immediate consultation with the attending radiologist and

pathologist should be available as needed. First, a radiologist identifies the area to be biopsied.

Through a process known as wire localization, a wire is positioned in the abnormal breast tissue to

identify the area to be cut out and removed during the breast biopsy surgery. Next, the patient is taken

to the operating room where she is placed under general anesthesia or a local anesthesia with sedation.

A surgeon makes a 1 to 2-inch incision in the breast and removes the localization wire and a large

section of tissue, typically about the size of a golf ball. The incision in the breast is then closed with

stitches and covered with a protective bandage. Because of the hospital and surgical resources needed to perform the operation, open surgical

biopsies are more costly than other breast biopsy methods [53,66].

Investments and tools required to use the VABB technology

Vacuum effect is achieved by the use of a free-standing vacuum console (except VaCora®)

(which remains outside the MRI suite during MRI-VABB). Depending on VABB device, 3 imaging

modalities (US, S, MRI) need 1 (ATEC®), 2 (EnCor®) or 3 (Mammotome®) different consoles for

the procedure [20,39,43]. Reusable adapter is important for an effortless insertion of the biopsy needle

and foot pedal allows a single and continuous cycle of tissue acquisition and collection [20,69,70].

Console is connected to the biopsy probe (or handpiece) by plastic tubing and needle also is mounted

to a probe [71]. Probes with needles and side collection chambers, tubing sets and debris canisters are

all disposable components [20,72]. Special biopsy grid or grid cube is used in MRI-VABB as a lesion

target system [45,73]. Dedicated prone tables and upright systems for biopsies are required [73].

Also, some more disposable items are required for every procedure: marker clip, surgical

scalpel, sterile gloves, compreses, drapes, little pot with a solution of 10 % formaldehyde to fixate the

tissue/specimen, few syringes with needles to administer the anaesthetics, some sterile ultrasound gel

(for US-VABB) [46].

Training and information needed to use the VABB technology

According to the quality guidelines of the Minimally Invasive Breast Biopsies Working

Group (MIBB group) in Switzerland, the operator for VABB procedures must be a specialist in

radiology, gynaecology, obstetrics or surgery. Before being allowed to operate independently, the

operator must complete a workshop with successful interventions on a phantom and five supervised

interventions when the method is established at their institute or 20 interventions under supervision

when the method is newly introduced at their institution. For maintenance of qualifications, each

operator must perform at least 12 interventions per year, with a minimum of 20 interventions per

institution per year. Using an 11G needle or bigger depending of the size of the lesion at least 12

samples should be taken [36].

According to Interdisciplinary Consensus Recommendations for the use of Vacuum-Assisted

Breast Biopsy under Sonographic Guidance (German Society of Senology), the investigator should be

a specialist and should have more than 2 years of experience performing breast sonography. He should

provide evidence of having conducted a minimum of 600 breast sonographies, of which at least 200

cases were pathological. The investigator should also provide evidence of at least 50 documented

ultrasound-guided interventional procedures. Attending a special VABB course is recommended and

the first 10 examinations should be conducted under the supervision of an investigator with experience

performing VABB [48].

In France, training in MRI-guided vacuum-assisted biopsies with histological confirmation

under the supervision of a specialist is required before a practitioner can work alone. The initial

32

training involves three procedures in France (as access to MRI is still limited) but 20 procedures are

required according to the guidelines from The European Society of Breast Imaging and then a

minimum of 25 procedures per year to maintain competence [44,45,74].

Discussion

For decades, small samples of tissue have been obtained using a needle to diagnose lesions in

many anatomical locations. Breast lesions were identified as particularly suitable for the technique due

to their accessibility [56]. With the continuous advancement of diagnostic and treatment technology

for BCa, collection of diseased tissue has undergone gradual transition; needle biopsies and fine needle

aspiration cytology have essentially replaced surgical excisional biopsy.

The advantages of using FNA include reduced morbidity, quicker procedure time, and less

side effects or complications. Comparing to FNA, needle biopsy yields more tissue for better

diagnostic assessment and ancillary studies, as well as allowing assessment of stromal invasion in

malignant lesions. With the advent of imaging detection of early diseases, non-palpable lesions have

become increasingly detected, and these lesions are not amenable to FNA assessment, with needle

biopsy becoming the mainstay for preoperative diagnosis. Needle biopsy includes core needle biopsy

and vacuum-assisted breast biopsy [24,65]. However, compared to FNA and CNB, VABB can remove

larger and multiple tissue samples in a single breast insertion [46]. Also, numerous studies attest that

percutaneous VABB is less invasive, causes less damage compared to open surgery [47]. In terms of

cost effectiveness in comparison with reference standard, many studies state that VABB brings

advantages because it is a well-tolerated method and reduces time off work [37,42,75,76]; the entire

procedure takes half an hour and the patient may be discharged from the hospital immediately after the

intervention without hospitalization. A number of European cost analyses have reported large savings

related to VABB compared with excisional surgery [48]. However, with reference to CNB, VABB is

approximately 1.22 times costlier [51,76].

VABB is currently recommended for stereotactic and MRI-guided interventions. US-guided

VABB is not generally indicated, because the less expensive core biopsy procedure frequently

achieves the same objective, however the advantage of this procedure is real-time visualisation. US-

guided VABB might be indicated as a therapeutic procedure for histology proven benign lesions in

selected situations [36].

While much progress has been made, there is still room for improvement through

development of new technologies that increase accuracy, safety, and cost-effectiveness, e.g., Digital

Breast Tomosynthesis (DBT), which is rapidly emerging as a relatively new imaging modality able to

detect breast lesions not visible at mammography. Consequently, percutaneous CNB on DBT-detected

lesions are going to increase [47,65]. Additionally, MRI-guided VABB should become more common

in order to capitalize on breast MRI, which is already widely performed.

It is also believed that the role of VABB, which is currently used to remove benign breast

lesions, will be expanded to treat malignant tumors. This would provide, in the near future, a

minimally invasive procedure not only for diagnosis, but also for treatment [47]. However, the

complete excision of microcalcifications is not to be considered an advantage compared to other

techniques for percutaneous VABB needle biopsies since the goal is not therapeutic [42].

33

SAFETY

Adverse events

Adverse events related to diagnostic VABB technology were reported in 7 case series

[37,42,55,75,77,78,79] (n=2697); they were divided into 3 groups: device and/ or procedure related,

serious and non-serious adverse events. It must be noted that significant differences in rates are due to

differences in the number of patients included in case series. Also, 2 case series [42,78] reported the

number of lesions (instead of the number of patients) included in case series and because of that,

adverse events were calculated from lesions. However, only a small number of people experienced

VABB for a few times during the same procedure, so this should not significantly distort the results.

Overall, adverse events and their incidence rate were reported in 7 case series

[37,42,55,75,77,78,79] after VABB procedure: infection 0%, scar formation 14.6% (small: 11.8%,

moderate/ severe: 2.8%), skin ecchymosis 2.3–19%, intraoperative bleeding 0.5–21.3% (small: 17.4%,

moderate/ severe: 0.5–3.9%), haematoma 0.1–41.3% (small: 1.1–41.3%, moderate/ severe/ with

surgical intervention: 0.1–6.2%).

Also, adverse events could be analysed according to assignment to 3 groups.

Intraoperative bleeding which was reported in 3 case series [42,78,79] was an only device

and/ or procedure related adverse event; the incidence rate varied from 0.5% (2/393 lsns.) [78] to

21.3% (38/ 178 pts.) [79]. Although a high rate was reported [79], most of cases were classified as

small bleeding – 31/ 178 pts. (17.4%). In 2 case series [78,79], six patients experienced moderate/

severe intraoperative bleeding due to which VABB procedure had to be aborted. The best prevention

of bleeding from the biopsy site seems to be a pressure dressing applied during the initial 24 hours,

also preventing pain which may be associated with bleeding and the growing hematoma inside the

breast [37].

Infection, haematoma with surgical intervention or moderate/ severe haematoma and

moderate/ severe scar formation were titled as serious adverse events and reported in 3 case series

[37,55,79]; the incidence rate of these complications varied from 0% [55] to 6.2% (11/ 178 pts.) [79].

Although infection was mentioned as an adverse event in 1 case serie [55], there was no case of a

diagnosed infection of the biopsy site. 1 patient (1/ 1177 pts., 0.1%) in one case serie [37] required

emergency surgical intervention of the haematoma. It is not reported how other patients (11/ 178 pts.

6.2%) who experienced moderate/ severe haematomas were treated [79].

Non-serious adverse events – skin ecchymosis, small haematoma, small scar formation –

were reported in 6 case series [37,42,55,75,77,79]; the incidence rate varied from 1.1% (1/ 88 pts.)

[75] to 41.3% (74/ 179 pts.) [55]. Although the VABB technology is supportive for blood suction out

of the biopsy cavity to reduce the chance of haematoma, however, the most common complication

after the procedure is haematoma [37,42,55,75,77,79]. Still, most of haematomas are small (1.1–

41.3%) and not require surgical intervention or hospitalization. In addition to the studies reporting

small scar formation or small haematoma, 2 case series [37,75] reported skin ecchymosis 2.3–19%; 1

case serie [37] stated there were skin ecchymosis without haematoma development.

1 case serie [79] compared VABB systems (Mammotome® and ATEC®) with different

needle diameters (8G, 9G, 11G, 12G) regarding intraoperative bleeding, haematoma and scar

formation in 178 cases of S-VABBs. Results showed more interventional bleedings (p<0.001) and

post-interventional haematomas (p=0.029) with the larger needle sizes significantly for Mammotome®

(11G vs. 8G) and not significant (p=0.799, p=0.596, respectively) for ATEC® (12G vs. 9G). On the

one hand, with Mammotome® system it can be explained by a larger biopsy cavity with a greater area

of injured breast tissue caused by rotating cutting knife. On the other hand, the similar bleeding rates

of the two needle sizes with ATEC® system are obviously more influenced by the rotating cutting

knife causing more fragmentation than by the biopsy cavity size.

The comparison of the 11G Mammotome® system revealed significantly less bleedings

(p=0.015)/ haematomas (p=0.001) compared to the ATEC® 12G system while there were no

34

significant differences for the large systems; it is considered that the correlation of tissue fragmentation

of the specimen and tissue injuries in the biopsy cavity are cause for higher bleeding and haematoma

rates with the ATEC® system.

No significant correlation was found between scar formation, VABB system or needle size

and no correlation between risk of scar formation after bleeding or haematoma with the examined

VABB systems or needle size.

One included case serie [80] had the alternative technology – CNB, however, adverse events

were not provided and not analysed; none of the included case series reported adverse events related to

reference standard. Also, information about harms related to frequency of applying the technology;

changes in frequency or severity of harms over time was not provided or analysed. Information

considering occupational and environmental safety was not reported as well.

False positive/ negative findings

False positive/ negative findings were reported in 16 case series (of 19)

[35,37,42,75,76,77,78,80,81,82,83,84,85,86,87,88].

False positive (FP) rate equalled 0% in all included studies. It can be explained because

occasionally VABB removes the entire target lesion that is being biopsied, rendering subsequent

surgical biopsies unable to confirm the findings of the index test procedure. In such cases of VABB

diagnoses of malignancy, it is considered that VABB results are true positive instead of FP as

malignancy was completely removed at biopsy [89].

A false negative (FN) finding was defined as one that was diagnosed as benign disease, but

was subsequently found to be cancer possibly due to a failure of obtaining a part of cancerous tissue of

cancer lesions at the previous biopsy [90]. FN values ranged from 0% [42,75,76] to 23.2% [88] in all

included studies. However, in some studies FN rate could be analysed according to specific imaging

modality.

US-VABB FN findings. 1 case serie [37] was included in this assessment where patients

(n=152) were biopsied only with ultrasound guided VABB and 10G/ 11G needles; FN rate after

surgical excision was equal 1.3% (2/ 152 pts.).

S-VABB FN findings. In 5 case series [35,42,75,78,86] patients (n=1419) were biopsied only

with stereotactic guided VABB (8G, 10G, 11G needles). However, 2 studies [42,78] had two groups;

the main difference was different needle sizes used for biopsies – 10G vs. 11G [42] and 8G vs. 11G

[78]. The standard size of needles is usually 10G, 11G or 12G, whereas 8G or 9G needles are used for

larger lesions and therapeutic excisions [79]. Results show that FN rate in 5 studies varied from 0%

[42,75] to 19.4% (114/ 589 pts.) [86]. In case series [42,78] with two groups, FN values were lower

when bigger needle size was applied: 10G (FN 0%) vs. 11G (FN 3%) [42], 8G (FN 4.9%) vs. 11G (FN

6.7%) [78].

MRI-VABB FN findings. Biopsies (n=368) in 4 case series [83,84,85,88] were performed

only with MRI-guided VABB. All cases used 9G needles and ATEC® vacuum-assisted biopsy

system. FN values varied from 6% (4/ 67 pts.) [83] to 23.2% (16/ 69 pts.) [88].

Only one case serie [80] had alternative for VABB – core needle biopsy with 14G needle; in

this study FP values for both technologies (VABB and CNB) were 0%, however, FN value was higher

in CNB patients – 42.1% (8/19 pts.) vs. 9.1% (1/ 11 pts.). VABB was performed with stereotactic and

ultrasound imaging modalities, different size needles (7G, 8G, 10G, 11G).

Misinterpretation of tests, based on FP and FN findings, may lead to over- or undertreating

patients. While FP results may cause worry, anxiety, distress and perceptions of BCa risk even several

years later, physical issues related to diagnostic procedures and economic costs, a FN finding can give

a false sense of security even though the cancer is present as well as delay in treatment [91,92].

35

Discussion

It is always desirable to have a definitive pre-operative diagnosis because early detection of

BCa improves the chance of cure and thereby saves lives. Among percutaneous biopsy techniques,

VABB obtains large tissue samples to alleviate some of the limitations associated with conventional

percutaneous biopsy techniques. The major advantage of VABB is the chance to withdraw a number of

samples sufficient for an accurate diagnosis with a single insertion of the needle and even, in some

cases, to completely remove the lesion; a 10-fold greater tissue volume is obtained per core with

VABB compared with CNB [42,45,76].

In general, these complications are possible after VABB: skin ecchymosis, haematomas at the

site of the biopsy, bleeding, pain, skin and pectoral muscle damage, vasovagal reactions [37,51,90]; the

last two noted were not reported in the included studies. Literature data also mentioned isolated cases

of pneumothorax and infectious complications, yet these were not reported in this assessment as well

[37]. The most common complication of VABB is haematoma, occasionally requiring emergency

surgical intervention and bleeding.

Any needle biopsy procedure may result in bleeding or infection, although the rate of

significant haematoma requiring drainage or infection requiring antibiotic treatment is only 0.2%.

Adverse or allergic reactions to medications, latex, disinfectant solutions, and tape or adhesives are

also possible but rare. To minimize the risk of bleeding, patients on anticoagulation therapy need to

have their treatment stopped or adjusted. Also, immediately after the biopsy needle is withdrawn from

the breast, compression of the biopsy site is performed to achieve hemostasis [48,93].

VABBs differ with respect to the use of imaging, the use of needles of varying diameter, the

numbers of samples taken. These and other factors may affect the rate of complications. For example,

some biopsy procedures may retrieve larger amounts of tissue, improving test performance, but the

retrieval of larger amounts of tissue may also result in more complications, such as bleeding [89].

Some studies suggested that VABB method led to increased bleeding and performing biopsies

with patients seated upright was associated with increased incidence of vasovagal reactions; however,

results were reported in a way that precluded quantitation of the relative risk [89,93]. Moreover,

according to literature [57,75,89], information about the dissemination or displacement of cancer cells

during the VABB procedure was provided by a small number of studies with various designs (and

experimental studies), however, they were not regarded as clinically relevant; the significance and true

incidence of this phenomenon remains uncertain.

Comparative studies with VABB and excisional surgery concerning complication rates,

postoperative pain, and periods of absence from work have not been published thus far [48]; based on

the literature data from indirect comparisons and expert opinion, open biopsy appeared to be

associated with an increased incidence of adverse events (including serious adverse events) compared

to VABB [89]; complications, the duration of the procedure, costs, possible scarring, and breast

deformations tend to seek less invasive and cheaper methods [37,77].

According to scientific data, the false negative rate of VABB is significantly lower than that

of CNB or FNA [76]. Studies have shown that FN results after S-VABB vary between 0.45% and

22.2% [75], which is similar to results found in this assessment (0–19.4%). MRI-VABB showed the

highest rate of FN (compared to other imaging modalities) in this assessment – 6–23.2%. Literature

data reports, FN rates could vary from 13% to 57% [85]. These seemingly elevated FN results on

MRI-VABB likely relates to sampling not performed under real-time direct visualization and that

lesion targeting cannot be as easily verified [94].

36

CLINICAL EFFECTIVENESS

Test accuracy

The test accuracy is based upon a one-sided comparison between the results of the index test

and those of the reference standard. Any discrepancy is assumed to arise from error in the index test. It

is believed that surgical excision is 100% reliable, still it is important to note that the assumption of

100% accuracy for the reference standard rarely holds true in practice. Test accuracy consists of

sensitivity, specificity, positive predictive value and negative predictive value. Also, the outcome of

interest in this assessment was underestimation rate. Reference standard which was surgical excision

was used in all case series included in the clinical effectiveness domain, except two studies [55,95]

which were included for the assessment of quality of life.

Overall sensitivity was reported in sixteen studies

[35,37,42,75,76,77,78,80,81,82,83,84,85,86,87,88] and varied from 0% to 100%. Seven case series

[77,81,82,83,85,86,88] reported that sensitivity is equal to 0% and three case series [42,75,76] stated

that sensitivity is 100%. Also, six studies [35,37,42,78,84,87] valued VABB sensitivity from 88.9% to

98.4%. Overall specificity was reported in all sixteen included studies

[35,37,42,75,76,77,78,80,81,82,83,84,85,86,87,88] and was 100%.

Positive/ negative predictive values were reported in all 16 studies; positive predictive value

(PPV) ranged from 0% [77,81,82,83,85,86,88] to 100% [35,37,42,75,76,78,84,87], and negative

predictive value (NPV) ranged from 75.7% [87] to 100% [42,75,76].

Overall underestimation rate varied from 0% to 23.2% (from 0 to 114 patients were

incorrectly classified as not having a BCa) in sixteen studies

[35,37,42,75,76,77,78,80,81,82,83,84,85,86,87,88]. However, underestimation rate mostly varied from

0% to 7.6% (from 0 to 16 patients incorrectly classified as not having a BCa)

[35,37,42,75,76,78,81,82,83,84,87].

Test accuracy according to imaging modality

VABB was guided with three different imaging modalities (ultrasound, stereotactic or

magnetic resonance) in all included studies, except one [87] where this information was not applicable.

Some patients included in clinical effectiveness analysis were biopsied with VABB conjuncted with a

single imaging modality: US-VABB [37], S-VABB [35,42,75,78,86], MRI-VABB [83,84,85,88];

however, some patients had VABB procedure with different imaging modalities in the same study:

US-VABB and S-VABB [76,77,80], or S-VABB and MRI-VABB [82], or US-VABB and S-VABB

and MRI-VABB [81].

Sensitivity, specificity and PPV/ NPV varied according to the different imaging modality. S-

VABB sensitivity varied from 0% [86] to 100% [42,75]. However, three studies [35,42,78] valued S-

VABB sensitivity from 89.2% to 94.7%. MRI-VABB sensitivity in three case series [83,85,88] was

equal to 0% and one study [84] reported sensitivity of 88.9%. US-VABB sensitivity reported in one

study [37] and was 98.4%. All imaging modalities had specificity value of 100%.

Positive predictive value in all imaging modalities ranged from 0% to 100%, however four

[35,42,75,78] of five studies stated that S-VABB value is 100% and three [83,85,88] of four studies

stated that MRI-VABB value is 0%. Though negative predictive value had a less considerable ranges

in all imaging modalities. Negative predictive value of S-VABB ranged from 80.6% to 100%

[35,42,75,78,86], NPV of MRI-VABB ranged from 76.8% to 94% [83,84,85,88], and NPV of US-

VABB was reported in only one study [37] and it was 93.3%.

Underestimation rates according to imaging modalities were: US-VABB – 1.3% (2 of 152

patients were incorrectly diagnosed as not having a BCa) [37], S-VABB – 10.9% (155 of 1419

patients) [35,42,75,78,82,86], and MRI-VABB – 15.2% (56 of 368 patients) [83,84,85,88].

37

Test accuracy according to needle size

VABB was performed using different needle available in a wide variety of outer diameters

described by gauge numbers (7G, 8G, 9G – large core, and 10G, 11G, 12G, 13G – small core). Two

studies [75,95] did not reported the size of needles and two studies [80,81] had a mixed information

about needle sizes. Also, one study [82] compared 8G/ 9G needles with 9G/ 10G, however this

information was assigned to a large core group.

Sensitivity in a large core group varied from 0% [82,83,85,88] to 91.5% [78]; however, three

studies [78,84,87] stated that sensitivity in this group is 88.9–91.5%. On the other hand, sensitivity in a

small core diameter group varied from 0% [77,86] to 100% [42,76]; however, four studies

[35,37,42,78] stated that sensitivity in this group is 89.2–98.4%. Specificity according to the needle

diameter in both groups was 100% [35,37,42,76,77,78,82,83,84,85,86,87,88].

Positive predictive value in the large core group ranged from 0% [82,83,85,88] to 100%

[78,84,87]. The same was in the small core group – PPV ranged from 0% [77,86] to 100%

[35,37,42,76,78]. Meanwhile negative predictive value in the large core group was 75.7–94%

[78,82,83,84,85,87,88], while NPV in the small core group was 80.6–100% [35,37,42,76,78,86] (in

most cases NPV was 80.6–93.3%).

Underestimation rates according to needle sizes were: large core – 9.1% (76 of 834 patients

were incorrectly diagnosed as not having a BCa) [78,82,83,84,85,87,88], and small core – 10.6% (148

of 1400 patients) [35,37,42,76,77,78,86].

Test accuracy in comparison with alternative

Only one retrospective case serie [80] had alternative for VABB – core needle biopsy with

14G needle; patients after VABB procedures or CNB procedures had the same reference standard

(surgical excision). Moreover, this study included 70 patients (mean age was 55 years), and some of

them underwent CNB and subsequent VABB procedure. All in all, patients were classified into two

groups, where 11 patients received VABB and subsequent surgical procedure (9 of 11 also underwent

CNB), and 19 patients who underwent CNB and subsequent surgical procedure (9 of 19 also

underwent VABB and were dublicated).

The probabilities that a test will indicate 'disease' among those with the disease (sensitivity)

were 83.3% (VABB) and 0% (CNB), and the fraction of those without disease who will have a

negative test result (specificity) were 100% for both tests. However, the percentages of patients with a

positive test who actually have the disease (PPV) were 100% and 0%, respectively; the percentages of

patients with a negative test who do not have the disease (NPV) were 83.3% and 57.9%, respectively.

In this case underestimation rates were quite different: 9.1% (1 of 11 patients) for the VABB

and 42.1% (8 of 19 patients) for the CNB [80].

Health-related quality of life and patient satisfaction

Two studies [55,95] reported quality of life (QoL) and patient safisfaction outcomes. In one

prospective study [95] of 90 women included, 45 underwent digital breast tomosynthesis guided

VABB (S-VABB (DBT)) and 45 digital mammography guided VABB (S-VABB (MMx)). Biopsy

experience was described with the Testing Morbidities Index (TMI), a validated instrument for

assessing short-term QoL related to diagnostic testing. Women in the S-VABB (DBT) group have a

decreased short-term QoL (higher mean of scores) compared to the S-VABB (MMx) group,

emphasizing a worst biopsy experience in terms of pain or discomfort before and during the test (2.6–

2.7 and 2.5–2.6 (mild/ moderate), respectively), fear or anxiety before and during the test (3.1–3.2 and

3.0 (moderate), respectively) and regarding physical (2.4 and 2.2 (mild problems), respectively) and

38

mental (3.1 and 2.8 (moderate problems), respectively) function after testing [95]. In this case, S-

VABBs (DBT) were less tolerated than S-VABB (MMx) ones [95]. However, patient age was a

significant independent predictor of TMI score (p>0.05). TMI scores were lowest in the youngest age

group, with short-term QOL decreasing as long as the decrease in patient age [95].

Same study [95] also included questions about the patient’s satisfaction, such as “the staff

showed concern for my worries” and “the doctor explained what to expect during the biopsy”.

However, overall satisfaction resulted similar for both procedures (Med.=3 (somewhat disagree)) [95].

Also, the level of embarrassment during testing resulted similar for both procedures (Med.=3

(moderate)) [95].

Another retrospective study [55], which reported patient satisfaction, included 189 patients, of

which 150 patients received 9 gauge needle VABB while using ATEC® biopsy device and 39 patients

received 11 gauge needle VABB using Mammotome® system. Comparing the two biopsy devices no

significant difference was found regarding the patient condition while undergoing (p=0.25; 2.6 (very

good/ good) and 2.2 (very good), respectively for devices) and after (p=0.2; 2.2 (very good) and 1.8

(excelent/ very good), repectively) the biopsy. However, the ATEC® system was significantly more

frequently associated with self-reported complications (p=0.005; 41.3% and 17.9%) and 43.5%

patients of all self-reported complications (n=69) reported severe pain [55].

In both groups (ATEC® and Mammotome®) patients were mostly satisfied with the cosmetic

result after the biopsy (97.3% and 97.4%, respectively) and would again prefer VABB to an open

surgical biopsy (88% and 92.3%, respectively) [55]. Also, older women evaluated the procedure as

less consciousness-affecting (condition during the procedure) than younger (p=0.02), and therefore the

younger group announces a higher frequency (p=0.02) of complications. Moreover, patients diagnosed

with a malignant lesion rated the VABB statistically significantly worse in terms of condition during/

after the procedure and in evaluation of the cosmetic result after the biopsy (p=0.011; p=0.035;

p=0.024, respectively) than those with a benign histology [55].

Discussion

There was conducted an assessment of the benefits and risks of breast biopsy methods for

breast cancer diagnosis, with respect to test performance, underestimation rates, and patient-relevant

outcomes [89].

There is believed that benign papillomas diagnosed at CNB with imaging concordance may

be safely managed with clinical and imaging follow-up. This suggests that conservative management

with imaging follow-up as opposed to surgical excision may be appropriate in most cases where an

initial diagnosis is made with VABB [81]. However, others advocate surgical excision to exclude any

associated malignancy [81]. In this assessment as a reference standard only a pathological

confirmation (following open biopsy or excisional surgery) was chosen, although the reference

standard in the reviewed studies was a combination of clinical follow-up and pathologic confirmation

(following open biopsy or excisional surgery). In this assessment was assumed that pathologic

confirmation have a timely result and a minor measurement error than follow-up. It is unlikely that this

assumption is exactly true (e.g., some degree of diagnostic error is possible for pathologic

examination), however, clinical follow-up may provide less accurate information in at least two years.

However, it is believed that the error rate of the reference standard (pathological confirmation) is low

enough that its influence on estimates is unlikely to be substantial [89]. All in all, surgical excision is

still warranted particularly if there is atypia or calcifications on the core biopsy, the patient is

postmenopausal, the lesion is peripheral, or the patient has a personal history of breast cancer [83].

VABB removes a greater amount of material, thus reducing the likelihood of preoperative

underestimation (less frequent underdiagnosis of malignancies), as well as the need to repeat the

procedure due to the inadequacy of sampled tissue [36,42,83]. The larger vacuum-assisted devices

(8G/ 9G) may provide wider sampling of the imaging target and may lower the upgrade rate for a

variety of lesions [42,83]. Significantly better performances were observed when greater calibre

differences were considered, and a single value in the Gauge scale did not lead to superior

39

performance [42]. However, previous investigators have suggested that no single needle type is

suitable in every case, as performance varies between institutions and for different lesion types, also

the choice of needle must take into account local biopsy performance data, risk of complications and

resource considerations (cost of disposables and operator time) [51].

Optimal selection of CNB or US-VABB for percutaneous breast biopsy has not been well

established [96]. Ultrasound-guided VABB is not generally indicated, because the less expensive core

biopsy procedure frequently achieves the same objective. Ultrasound-guided VABB might be

indicated as a therapeutic procedure for histology proven benign lesions in selected situations [36].

The fact is that choice often depends on personal preference [96].

The strength of the VABB systems lies, however, in their high predictive value for the

absence of malignancy (NPV) [42]. VABB in the breast has been adopted for first-line diagnosis in

North America and Europe, however, additional costs of VABB have inhibited widespread first-line

diagnostic use in the UK and 14G CNB remains the standard technique in many centres. Greater

diagnostic accuracy using VABB may prove cost-effective if diagnosis with VABB leads to fewer

repeat operations, although the difference in cost between VABB (£250) and CNB (£25) is appreciable

[51]. Nevertheless, VABB costs much less than open biopsy: a number of European cost-analyses have

reported a savings of approximately 82 % compared with open biopsy [48].

When the discussion turns to what is appropriate for the patients, they were mostly satisfied

with the cosmetic result after the biopsy and would again prefer VABB to an open surgical biopsy

[51,55,95]. However, patients diagnosed with malignant disease at VABB judged the biopsy

procedure, the complication rate and the cosmetic result more negative than the group with benign

findings. This might be influenced in retrospective view by the upcoming procedures that patients

underwent, as oncological treatment and open surgery had to be performed [55]. Also, an obvious

difference was seen in needle diameter (9G vs. 11G): despite a higher accuracy, larger core was

suggesting a higher traumatic potency [55].

In summary, VABB is a minimally invasive intervention of the breast and is superior to open

biopsy in regards to cosmetic outcome, the duration of the procedure, and postoperative internal scars.

Comparative studies concerning disease specific-mortality, disease specific-morbidity, postoperative

pain, and periods of absence from work have not been published thus far [48].

40

CONCLUSIONS

1. Breast cancer is now the second most common cause of cancer death in more developed

regions; however, 89% of women diagnosed with breast cancer are still alive 5 years after their

diagnosis, which is due to detection and treatment. Mammography screening, every 2 years,

has shown the greatest mortality reduction benefit in the age group of 50–69 years. If

something suspicious is found during a screening exam, a pathological diagnosis should be

based on a biopsy.

2. Currently, there are four CE and FDA approved systems in routine use: Mammotome®,

VaCora®, EnCor® and ATEC®; these systems also have few models and versions. All VABB

systems can be used with stereotactic, ultrasound or magnetic resonance guidance. Only during

US-VABB real-time visualisation is available.

3. The most common complications of VABB are intraoperative bleeding (0.5–21.3%) and

haematomas (0.1–41.3%). The incidence rate of all adverse events varies from 0% to 41.3%,

however, most of the complications are small and non-serious. Biopsy needle diameter may

affect the complication rate, still, in order to confirm this, further studies are required.

4. False positive rate equalled 0% in all included studies, because occasionally VABB removes

the entire target lesion that is being biopsied, rendering subsequent surgical biopsies unable to

confirm the findings of the index test procedure. False negative values ranged from 0% to

23.2%. With respect to specific imaging modality, the highest false negative rate was reported

with MRI-VABB – 6–23.2%. False negative findings can give a false sense of security even

though the cancer is present as well as delay in treatment.

5. Overall VABB sensitivity varied from 88.9% to 98.4%, specificity was equal to 100%. Overall

underestimation rate varied from 0% to 23.2% (from 0 to 114 patients were incorrectly

classified as not having a breast cancer (according to ICD-10: C50 or D05)). According to

different imaging modalities S-VABB rates (sensitivity: 89.2–94.7%, underestimation: 10.9%

(155 of 1419 patients)) were better than MRI-VABB rates (sensitivity: 0%, underestimation:

15.2% (56 of 368 patients)). Needle size for breast biopsy seems to have no particular impact

on test accuracy.

6. Patients were mostly satisfied with the cosmetic result after the biopsy (97.3%) and would

again prefer VABB to an open surgical biopsy (88–92.3%). However, scores were lower in the

youngest age group, with short-term QOL decreasing as long as the decrease in patient age.

Also, patients diagnosed with a malignant lesion rated the VABB statistically significantly

worse (p=0.011–0.035) than those with a benign histology.

41

RECOMENDATIONS

1. Considering the significantly higher cost of VABB compared to CNB and the usage of VABB

technology when alternative technologies provide negative results (and still high cancer risk

exists), VABB should be offered only to appropriately selected patients.

2. The results from diagnostic accuracy studies require clarification and confirmation in

comparative prospective studies, where safety and efficacy of the VABB technology would be

compared with the results of alternative technologies (CNB, FNA) or other VABB systems.

42

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74. Wallis M, Tarvidon A, Helbich T, Schreer I. Guidelines from the European Society of Breast

Imaging for diagnostic interventional breast procedures. European Radiology. 2007 Feb; 17(2):

581–588. Available from: http://link.springer.com/article/10.1007%2Fs00330-006-0408-

x#Sec6

75. Agacayak F, Ozturk A, Bozdogan A, Selamoglu D, Alco G, Ordu C, Pilanci KN, Killi R,

Ozmen V. Stereotactic vacuum-assisted core biopsy results for non-palpable breast lesions.

Asian Pacific Journal of Cancer Prevention. 2014;15(13):5171-4.

76. Debi U, Thulkar S, Sharma S, Sharma MC, Seenu V, Deo SVS, Agarwal S, Hari S. Role of

directional vacuum assisted breast biopsy in previously equivocal biopsies for breast masses

suspicious for malignancy. Malaysian Journal of Pathology. 2015 Apr;37(1):25-33.

77. Kibil W, Hodorowicz-Zaniewska D, Popiela TJ, Kulig J. Vacuum-assisted core biopsy in

diagnosis and treatment of intraductal papillomas. Clinical Breast Cancer. 2013 Apr;13(2):129-

32.

78. Venkataraman S, Dialani V, Gilmore HL, Mehta TS. Stereotactic core biopsy: Comparison of

11 gauge with 8 gauge vacuum assisted breast biopsy. European Journal of Radiology. 2012

Oct;81(10):2613-9.

79. Schaefer FK, Order BM, Eckmann-Scholz C, Strauss A, Hilpert F, Kroj K, Biernath-Wüpping

J, Heller M, Jonat W, Schaefer PJ. Interventional bleeding, hematoma and scar-formation after

vacuum-biopsy under stereotactic guidance: Mammotome(®)-system 11 g/8 g vs. ATEC(®)-

system 12 g/9 g. European Journal of Radiology. 2012 May;81(5):e739-45.

80. Parkin CK, Garewal S, Waugh P, Maxwell AJ. Outcomes of patients with lobular in situ

neoplasia of the breast: the role of vacuum-assisted biopsy. Breast. 2014 Oct;23(5):651-5.

81. Hawley JR, Lawther H, Erdal BS, Yildiz VO, Carkaci S. Outcomes of benign breast

papillomas diagnosed at image-guided vacuum-assisted core needle biopsy. Clinical Imaging.

2015 Jul-Aug;39(4):576-81.

https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/465694/nhsbsp20.pdf

https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/465694/nhsbsp20.pdf

http://www.associationofbreastsurgery.org.uk/media/4565/surgical_guidelines_for_the_management_of_breast_cancer.pdf

http://www.associationofbreastsurgery.org.uk/media/4565/surgical_guidelines_for_the_management_of_breast_cancer.pdf

http://www.emsor.es/wp-content/uploads/2011/01/Overview-of-minimally-invasive-breast-biopsies.pdf

http://www.emsor.es/wp-content/uploads/2011/01/Overview-of-minimally-invasive-breast-biopsies.pdf

https://www.somatex.com/tumark-flex-atec.html

https://books.google.lt/books?id=DdUmj7o8bKwC&pg=PA295&lpg=PA295&dq=disposable+handpiece+vacuum+biopsy&source=bl&ots=BWX3SJpBOp&sig=JJKpTXL8FrlBruF1HRUBO33lCnU&hl=lt&sa=X&ved=0ahUKEwjV7tub3MjRAhUG1BoKHR8uCEY4ChDoAQhTMA0#v=onepage&q=disposable%20handpiece%20vacuum%20biopsy&f=false




http://www.bardbiopsy.com/pdf/S120265-0_BARD_WasteManagement_WP_1_31_13_SAMPLE.pdf

http://www.bardbiopsy.com/pdf/S120265-0_BARD_WasteManagement_WP_1_31_13_SAMPLE.pdf

http://pubs.rsna.org/doi/full/10.1148/radiol.13120985

http://link.springer.com/article/10.1007%2Fs00330-006-0408-x#Sec6

http://link.springer.com/article/10.1007%2Fs00330-006-0408-x#Sec6

47

82. Dialani V, Venkataraman S, Frieling G, Schnitt SJ, Mehta TS. Does isolated flat epithelial

atypia on vacuum-assisted breast core biopsy require surgical excision? The Breast Journal.

2014 Nov-Dec;20(6):606-14.

83. Brennan SB, Corben A, Liberman L, Dershaw DD, Brogi E, Van Zee KJ, Morris E. Papilloma

diagnosed at MRI-guided vacuum-assisted breast biopsy: is surgical excision still warranted?

AJR. American Journal of Roentgenology. 2012 Oct;199(4):W512-9.

84. Rauch GM, Dogan BE, Smith TB, Liu P, Yang WT. Outcome analysis of 9-gauge MRI-guided

vacuum-assisted core needle breast biopsies. AJR. American Journal of Roentgenology. 2012

Feb;198(2):292-9.

85. Heller SL, Elias K, Gupta A, Greenwood HI, Mercado CL, Moy L. Outcome of high-risk

lesions at MRI-guided 9-gauge vacuum- assisted breast biopsy. AJR. American Journal of

Roentgenology. 2014 Jan;202(1):237-45.

86. Bianchi S, Bendinelli B, Castellano I, Piubello Q, Renne G, Cattani MG, Di Stefano D, Carrillo

G, Laurino L, Bersiga A, Giardina C, Dante S, Di Loreto C, Quero C, Antonacci CM, Palli D;

VANCB Study Group. Morphological parameters of flat epithelial atypia (FEA) in stereotactic

vacuum-assisted needle core biopsies do not predict the presence of malignancy on subsequent

surgical excision. Virchows Archiv. 2012 Oct;461(4):405-17.

87. Timpe L, Berkemeyer S, Puesken M, Tio J, Heindel W, Weigel S. Rates of presurgical

underestimation of breast cancer after standardized assessment of breast calcifications. RoFo.

2015 Jun;187(6):445-9.

88. Lourenco AP, Khalil H, Sanford M, Donegan L. High-risk lesions at MRI-guided breast

biopsy: frequency and rate of underestimation. AJR. American Journal of Roentgenology. 2014

Sep;203(3):682-6.

89. Dahabreh IJ, Wieland LS, Adam GP, Halladay C, Lau J, Trikalinos TA. Core Needle and Open

Surgical Biopsy for Diagnosis of Breast Lesions: An Update to the 2009 Report. Comparative

Effectiveness Review No. 139. (Prepared by the Brown Evidence-based Practice Center under

Contract 290-2012-00012-I.) AHRQ Publication No.14-EHC040-EF. Rockville, MD: Agency

for Healthcare Research and Quality. September 2014.

www.effectivehealthcare.ahrq.gov/reports/final.cfm

90. Ohsumi S, Taira N, Takabatake D, Takashima S, Hara F, Takahashi M, Kiyoto S, Aogi K,

Nishimura R. Breast biopsy for mammographically detected nonpalpable lesions using a

vacuum-assisted biopsy device (Mammotome) and upright-type stereotactic mammography

unit without a digital imaging system: experience of 500 biopsies. Breast Cancer. 2014

Mar;21(2):123-7.

91. Singleton JK, DiGregorio RV, Green-Hernandez C, Holzemer SP, Faber ES, Ferrara LR, Slyer

JT. Primary Care. An Interprofessional Perspective. Second Edition. Springer Publishing

Company. 2015. Available from:

https://books.google.lt/books?id=jJCKBQAAQBAJ&pg=PA19&lpg=PA19&dq=false+negativ

e+findings+could+delay+the+treatment&source=bl&ots=j1STnO7AIt&sig=bMrWTUSATX3v

3s9VYzRRkRlNzRY&hl=lt&sa=X&ved=0ahUKEwiKrdb6l-

fSAhXoApoKHXZBDl0Q6AEIMzAD#v=onepage&q=false&f=false

92. DeFrank JT, Brewer N. A model of the influence of false-positive mammography screening

results on subsequent screening. Health Psychology Review. 2010; 4(2): 112–127. Available

from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3160720/

93. Huang ML, Adrada BE, Candelaria R, Thames D, Dawson D, Yang WT. Stereotactic breast

biopsy: pitfalls and pearls. Techniques in Vascular and Interventional Radiology. 2014

Mar;17(1):32-9.

94. Heller SL, Moy L. Breast Oncology: Techniques, Indications, and Interpretation. 2017.

Available from:

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+negative+rate+of+MRI+vacuum+assisted+breast+biopsy&source=bl&ots=9gAlxuaH_V&sig

=ZFEquhMuOt6MxdgcruShVE-_Wo0&hl=lt&sa=X&ved=0ahUKEwic-

http://www.effectivehealthcare.ahrq.gov/reports/final.cfm

https://books.google.lt/books?id=jJCKBQAAQBAJ&pg=PA19&lpg=PA19&dq=false+negative+findings+could+delay+the+treatment&source=bl&ots=j1STnO7AIt&sig=bMrWTUSATX3v3s9VYzRRkRlNzRY&hl=lt&sa=X&ved=0ahUKEwiKrdb6l-fSAhXoApoKHXZBDl0Q6AEIMzAD#v=onepage&q=false&f=false





https://books.google.lt/books?id=g5w7DgAAQBAJ&pg=PA245&lpg=PA245&dq=high+false+negative+rate+of+MRI+vacuum+assisted+breast+biopsy&source=bl&ots=9gAlxuaH_V&sig=ZFEquhMuOt6MxdgcruShVE-_Wo0&hl=lt&sa=X&ved=0ahUKEwic-_mi74rTAhXjHJoKHTnDBAgQ6AEISTAG#v=onepage&q=high%20false%20negative%20rate%20of%20MRI%20vacuum%20assisted%20breast%20biopsy&f=false



48

_mi74rTAhXjHJoKHTnDBAgQ6AEISTAG#v=onepage&q=high%20false%20negative%20ra

te%20of%20MRI%20vacuum%20assisted%20breast%20biopsy&f=false

95. Tagliafico A, Gristina L, Bignotti B, Valdora F, Tosto S, Calabrese M. Effects on short-term

quality of life of vacuum-assisted breast biopsy: comparison between digital breast

tomosynthesis and digital mammography. The British Journal of Radiology.

2015;88(1056):20150593.

96. Uematsu T. How to choose needles and probes for ultrasonographically guided percutaneous

breast biopsy: a systematic approach. Breast Cancer. 2012 Jul;19(3):238-41.

97. EUnetHTA Joint Action 2, Work Package 8. HTA Core Model® Application for Diagnostic

Technologies version 3.0; 2016. Available from: http://meka.thl.fi/htacore/model/AE-tables-

diagnostics-3.0.pdf



http://meka.thl.fi/htacore/model/AE-tables-diagnostics-3.0.pdf

http://meka.thl.fi/htacore/model/AE-tables-diagnostics-3.0.pdf

49

APPENDIX 1: METHODS AND DESCRIPTION OF THE

EVIDENCES USED

The assessment was made on the basis of health technology assessment methodology

prepared by International European Health Technology Assessment Network ‘EUnetHTA’. The rapid

assessment was based primarily on a basic systematic literature search in the following sources:

• Cochrane Library database;

• PubMed (Medline);

• CRD database;

• Hand searches including articles from the manufacturers.

The systematic literature search was conducted with time limitation from 2012; systematic

literature search strategies are introduced further in Appendix 2.

Relevant articles for the ‘Safety’ and ‘Clinical effectiveness’ domains were selected by the

Chief specialists of Medical Technology division of VASPVT (State Health Care Accreditation

Agency under the Ministry of Health, Lithuania). Search filter for studies of diagnostic tests was not

used to increase search sensitivity. Also, systematic reviews on the topic were searched and their lists

of included studies were used to validate search strategy and to make sure all relevant studies were

identified. References were included or excluded according to the PICO-scheme described in the

summary.

In terms of study design, no HTAs or RCTs were found; only prospective and retrospective

case series were selected for answering questions related to the domains ‘Safety’ and ‘Clinical

effectiveness’. For the two other domains ‘Health problem and current use of the technology’ and

‘Description and technical characteristics’, no restrictions in terms of study design were applied.

In cases where questions within the domains ‘Health problem and current use of technology’

and ‘Description and technical characteristics of technology’ could not be answered using the

information retrieved from the basic systematic literature search described earlier, additional searches

within specific information sources (e.g. databases for clinical guidelines, websites of manufactures

etc.) and, if needed, hand searching were performed.

The quality of diagnostic accuracy studies was assessed by QUADAS-2 checklist (see

Appendix 5). The tool assesses study quality in four domains: patient selection, index test, reference

standard, and flow and timing. Each domain is assessed in terms of risk of bias, and concerns

regarding applicability (for the first three domains). Application of the tool results in a judgement of

risk of bias for each study categorised as low, high, or unclear. For assessing the quality of systematic

review, the AMSTAR checklist for systematic reviews was used (see Appendix 5). Also, the quality of

3 CSs (one for ‚Safety domain‘ (adverse events) and two for ‚Clinical effectiveness‘ domain (quality

of life)) was assessed using the IHE checklist for case series (see Appendix 5).

Study details, study population, results regarding efficacy/ effectiveness and safety of selected

studies were extracted into a data extraction tables (see Appendix 4).

Reporting of results

Study characteristics

Four prospective case series [35,76,79,95] and fifteen retrospective case series

[37,42,55,75,77,78,80,81,82,83,84,85,86,87,88] were included for effectiveness and safety assessment.

The majority of diagnostic studies [78,81,82,83,84,88] were conducted in USA (one study

[85] was written together with researchers from the United Kingdom), four studies [35,42,86,95] in

Italy, three studies [55,79,87] in Germany, two studies [37,77] in Poland. Also, one study from each of

the countries was included in the assessment: India [76], Turkey [75], and the United Kingdom [80].

Index test was vacuum assisted breast biopsy guided with different imaging modalities:

ultrasound, stereotactic or magnetic resonance. In some case series patients were biopsied with VABB

50

conjuncted with a single imaging modality: US-VABB [37], S-VABB [35,42,75,78,86,95], MRI-

VABB [83,84,85,88]. Two case series [55,87] did not report which imaging modality was used with

VABB. However, some studies [76,77,80,81,82] included patients who had VABB procedure with

different imaging modalities in the same study. 7G, 8G, 9G, 10G, 11G, 12G, 13G needle sizes with

VABB devices were used; two studies [75,95] did not report the size of needles. Four VABB systems

(Mammotome®, VaCora®, EnCor®, ATEC®) were used in the included case series.

Reference standard which was surgical excision was used in all case series, except three

[55,79,95]: one study [79] was included only for safety, two studies [55,95] were included for the

assessment of quality of life.

Only one case serie [80] had alternative for VABB – core needle biopsy with 14G needle;

patients after VABB procedures or CNB procedures had the same reference standard (surgical

excision).

Conflict of interest was reported in five (of 19) case series [35,77,80,81,86,95] and in all of

them it was stated as “none”. The source of funding was declared in four case series (of 19)

[35,81,86,95]: two studies [35,81] stated there were no source of funding, one study [95] had financial

support from university and one study [86] was supported by a grant from the “Ente Cassa di

Risparmio” of Florence-Italy.

Patient characteristics

A total of 5365 (range from 37 to 1177) patients were included in 18 of 19 studies. One study

[42] reported only number of lesions (n=169). Nevertheless, 279 of 5365 patients were included only

into quality of life analysis [55,95]. Also, exclusively one study [76] reported sex of the patients –

there was one man out of 43 patients.

All patients included in HTA were suspected for primary benign/ high-risk/ malignant breast

lesions, with median age from 48 to 61 years (range 22–87) in five studies [55,76,82,83,85] and with

mean age from 41.7 to 56.2 years (range 18–92) in thirteen studies

[35,37,42,75,77,78,79,80,81,83,84,88,95]. Also, one study [87] did not reported age of the patients and

in one study [86] information about age of included patients was not applicable.

Index test (VABB) was not available for all included patients: one of the included studies [78]

reported reduced number of lesions; therefore 4488 patients

[35,37,55,75,76,77,79,80,81,82,83,84,85,86,87,88,95] and 997 lesions [42,78] an index test as a total

of patients received. Surgical excision as a reference standard was used in 16 of 19 included case series

and was applied to 1262 patients [35,75,76,77,80,82,86,87,88] and 976 lesions [37,42,78,81,83,84,85].

Also, surgical excision as a reference standard was not used in three studies – two [55,95] had a

purpose to assess quality of life and patients’ satisfaction, and one [79] was used to evaluate rate of

complications.

Quality assessment

The quality of sixteen diagnostic accuracy studies

[35,37,42,75,76,77,78,80,81,82,83,84,85,86,87,88] was assessed by QUADAS-2 checklist; three case

series [55,79,95] without reference standard were assessed by using the Institute of Health Economics

(IHE) checklist.

QUADAS-2 consists of four key domains: patient selection, index test, reference standard,

flow and timing. Each domain is assessed in terms of the risk of bias and the first three are also

assessed in terms of concerns regarding applicability.

Ten diagnostic studies [35,42,77,78,81,82,83,85,87,88] had low risk of bias in patient

selection domain; six case series [37,75,76,80,84,86] had unclear risk of bias in patient selection,

mostly because of nonconsecutive patients or patients not from random sample were enrolled in a

study. All studies had low risk of bias in index test domain; however, in reference standard domain

only one [82] case serie had low risk of bias. All other studies had unclear risk of bias due to the

51

uncertainty if reference standard results were interpreted without knowledge of the results of the index

test. Flow and timing domain had the majority of quality problems: only in one study [86] risk of bias

was low, seven studies [42,75,77,80,81,84,85] had unclear risk of bias and eight studies

[35,37,76,78,82,83,87,88] had high risk of bias. It is suggested that this poor evaluation can be related

to the fact that follow-up was not analysed in this assessment (Question: did all patients receive a

reference standard? All answers: no.).

The quality of three case series [55,79,95] assessed by IHE checklist was affected by

retrospective or questionable information about study design, partially clear description of

intervention, some issues about outcome measures and length of follow-up.

More detailed information on the quality assessment can be found in Appendix 5.

Outcomes

Sensitivity was reported in sixteen studies [35,37,42,75,76,77,78,80,81,82,83,84,85,86,87,88]

and varied from 0% to 100%. Seven case series [77,81,82,83,85,86,88] reported that sensitivity is

equal to 0% and three case series [42,75,76] stated that sensitivity is 100%. Also, seven studies

[35,37,42,78,80,84,87] valued VABB sensitivity from 83.3% to 98.4%. Four [35,37,84,87] of these

seven studies were one-way (VABB was not compared with other VABB devices or alternative).

However, two studies [42,78] were comparing different needle sizes [78] or manufacturers [42]. In one

study [80] VABB results were compared with CNB results: VABB sensitivity was 83.3% and CNB

reported 0% sensitivity.

Specificity was reported in all sixteen included studies

[35,37,42,75,76,77,78,80,81,82,83,84,85,86,87,88] and was 100%. In one study [80] where VABB

was compared with CNB, both devices reported 100% specificity.

Positive/ negative predictive values were reported in 16 studies

[35,37,42,75,76,77,78,80,81,82,83,84,85,86,87,88]; PPV ranged from 0% to 100%, and NPV ranged

from 75.7% to 100%. In one study [80] VABB results were compared with CNB results: VABB

reported PPV/ NPV of 100/ 83.3% and CNBs’ PPV/ NPV were 0/ 57.9%.

False positive/ false negative values of VABB were reported in all sixteen case series

[35,37,42,75,76,77,78,80,81,82,83,84,85,86,87,88] that were included for effectiveness assessment.

Diagnoses of malignancy on VABB were assumed to be correct, whether or not a tumor was observed

upon surgical excision; all diagnoses of malignancy on VABB were classified as true positives instead

of false positive. This operational definition was adopted from the Agency for Healthcare Research

and Quality (AHRQ) report: Core Needle and Open Surgical Biopsy for Diagnosis of Breast Lesions:

An Update to the 2009 Report [89].

False positive values in all studies were equal 0%; false negative values ranged from 0%

[42,75,76] to 23.2 % [88]. False positive value of CNB [80] was 0%, false negative value – 42.1%.

The term “Underestimation rate” has been used in this HTA for lesions that were diagnosed

as high-risk or benign lesions at biopsy, but with final pathology at surgical excision changed the

malignancy (in situ (DCIS) or invasive (ICa)). Underestimation rate was reported in 16 case series

[35,37,42,75,76,77,78,80,81,82,83,84,85,86,87,88] and varied from 0% to 23.2%. In one study [80]

VABB results were compared with CNB results: VABB reported underestimation rate of 9.1% (n=1)

and CNB reported 42.1% (n=8).

Quality of life and patient-related outcomes (patient satisfaction, pain, etc.)

before/during/after the procedure were reported in 2 prospective studies [55,95] (n=279). One study

[95] is comparing S-VABB (DBT) with S-VABB (MMx) while other study [55] is comparing two

different manufacturers’ biopsy devices (ATEC® vs. Mammotome®).

Adverse events were reported in seven case series [37,42,55,75,77,78,79] (n=2697); all

adverse events were divided in three groups: device and/ or procedure related, serious, non-serious.

The most common adverse event was haematoma [37,42,55,75,77,79].

None of the studies provided information about disease specific-mortality.

52

APPENDIX 2: DOCUMENTATION OF THE BASIC SEARCH

STRATEGIES

Database: PubMed

Search date: 2016-11-16

Results: 135 hits.

Searches Results

1. breast 414908

2. (tumor OR cancer OR ?carcinoma* OR neoplasm* OR (non-cancerous OR benign)) 3829226

3. Breast Neoplasms[MeSH Terms] 243510

4. (((breast) AND (tumor OR cancer OR ?carcinoma* OR neoplasm* OR (non-cancerous OR

benign))) OR Breast Neoplasms[MeSH Terms] 337714

5. biopsy 3042194

6. Biopsy[MeSH Terms] 245731

7. (vacuum assisted) OR (vacuum-assisted) 3566

8. ((vacuum assisted) OR (vacuum-assisted)) AND (biopsy OR Biopsy[MeSH Terms]) 1005

9.

(((breast) AND (tumor OR cancer OR ?carcinoma* OR neoplasm* OR (non-cancerous OR

benign))) OR Breast Neoplasms[MeSH Terms]) AND (((vacuum assisted) OR (vacuum-assisted))

AND (biopsy OR Biopsy[MeSH Terms]))

683

10.

(((breast) AND (tumor OR cancer OR ?carcinoma* OR neoplasm* OR (non-cancerous OR

benign))) OR Breast Neoplasms[MeSH Terms]) AND (((vacuum assisted) OR (vacuum-assisted))

AND (biopsy OR Biopsy[MeSH Terms])) Filters: published in the last 5 years; Humans; English

135

Database: Cochrane Library


Results: 16 hits.

Searches Results

1. MeSH descriptor: [Breast Neoplasms] explode all trees 9912

2. breast 29865

3. tumo*r* OR cancer* OR ?carcinoma* OR neoplasm* 123786

4. benign OR non-cancerous 6297

5. #3 OR #4 127640

6. #2 AND #5 OR #1 24183

7. MeSH descriptor: [Biopsy] explode all trees 5791

8. biopsy 15173

9. #7 OR #8 16217

10. vacuum-assisted OR vacuum assisted 430

11. #10 AND #9 58

12. #6 AND #11 42

13. #6 AND #11, Publication Year from 2012 to 2016 16

Database: CRD database


Results: 2 hits.

Searches Results

1. MeSH DESCRIPTOR Breast Neoplasms EXPLODE ALL TREES 1771

2. (tumor OR cancer OR carcinoma OR neoplasm OR (non-cancerous) OR benign) 12574

3. (breast) 2845

4. #2 AND #3 2297

5. #1 OR #4 2442

6. (((vacuum assisted) OR (vacuum-assisted)) AND biopsy) 21

7. #5 AND #6 16

8. #7 FROM 07/11/2011 TO 07/11/2016 2

53

Flow charts of study selection

Table I. Flow chart showing selection of studies.

Records identified

through PubMed

(Medline) searching

(n = 135)

Scr

een

ing

In

clu

ded

E

ligib

ilit

y

Iden

tifi

cati

on

Records identified

through Cochrane

Library searching

(n = 16)

Records after duplicates removed

(n = 148)

Records screened

(n = 148)

Records excluded (n = 128) with

reasons:

Wrong population: n=9

Wrong intervention: n=34

Wrong comparator: n=2

Wrong study design: n=20

Wrong research question: n=36

Incomplete reporting of results: n=15

Only abstract available: n=1

Background: n=11

Full-text articles assessed

for eligibility

(n = 20)

(1 SR; 19 CS)

Studies included in qualitative synthesis: n=20

Effectiveness Domain: n=19 (1 SR; 18 CS)

Safety Domain: n=19 (1 SR; 18 CS)

Records identified

through CRD

database searching

(n = 2)

Additional records

identified through

other sources

(n = 20)

54

APPENDIX 3: QUESTIONS USED FROM HTA CORE MODEL

APPLICATION FOR DIAGNOSTIC TECHNOLOGIES (Version 3.0)

Health Problem and Current Use of the VABB Technology [97]

Element ID Research question

A0007 What is the target population in this assessment?

A0023 How many people belong to the target population?

A0002 What is the disease or health condition in the scope of this assessment?

A0003 What are the known risk factors for the breast cancer?

A0004 What is the natural course of the breast cancer?

A0005 What is the burden of breast cancer for the patient?

A0006 What are the consequences of the breast cancer for the society?

A0024 How the breast cancer is currently diagnosed according to published guidelines and in

practice?

A0025 How the breast cancer is currently managed according to published guidelines and in

practice?

A0001 For which health conditions and populations, and for what purposes is the VABB

technology used?

A0011 How much is the VABB technology utilised?

F0001 Is the VABB technology a new, innovative mode of care, an add-on to or modification

of a standard mode of care or replacement of a standard mode of care?

A0022 Who manufactures the VABB technology?

A0020 For which indications has the VABB technology received marketing authorisation or

CE marking?

A0021 What is the reimbursement status of the VABB technology?

Description and Technical Characteristics of the VABB Technology [97]


B0001 What are the VABB technology and the comparators?

B0002 What is the claimed benefit of the VABB technology in relation to the comparators?

B0003 What is the phase of development and implementation of the VABB technology and

the comparators?

B0004 Who administers the VABB technology and the comparators and in what context and

level of care are they provided?

B0009 What equipment and supplies are needed to use the VABB technology and the

comparators?

B0013 What kind of training and information is needed for the personnel/ caregivers using

the VABB technology?

Safety [97]


C0008 How safe is the VABB technology in relation to the comparator(s)?

C0004 How does the frequency or severity of harms change over time or in different

settings?

C0006 What are the consequences of false positive, false negative and incidental findings

55

generated by using the VABB technology from the viewpoint of patient safety?

C0007 Are the VABB technology and comparator(s) associated with user-dependent harms?

C0062 How can one reduce safety risks for patients (including technology-, user-, and

patient- dependent aspects)?

Clinical Effectiveness [97]


D0012 What is the effect of the VABB technology on generic health-related quality of life?

D0017 Were patients satisfied with the technology?

D1001 What is the accuracy of the VABB technology against reference standard?

D1002 How does the VABB technology compare to other optional tests in terms of accuracy

measures?

D1003 What is the reference standard and how likely does it classify the target condition

correctly?

D1006 Does the VABB technology reliably rule in or rule out the target condition?

D1007 How does VABB technology accuracy vary in different settings?

D1019 Is there evidence that the replacing test (VABB technology) is more specific or safer

than the old one?

D0020 Does use of the VABB technology lead to improved detection of the condition?

D0029 What are the overall benefits and harms of the VABB technology in health outcomes?

56

APPENDIX 4: DESCRIPTION OF THE EVIDENCE USED

Evidence tables of individual studies included

Table II. Evidence table for case series study details.

Study details Study population

Author, years [ref.] Country Study

design

CoI

SoF

No. of

pts./lsns.

Age

[range yrs]

Index test No.

of pts./lsns.

Ref. stand. No. of

pts./ lsns.

Mean size of

masses

[range cm]

Debi, 2015 [76] India Prosp. CS CoI: NR

SoF: NR

P43

(1M)

Med.=48

[22–73] P43 P31

2.9

[0.7–6]

Hawley, 2015 [81] USA Retr. CS CoI: None.

SoF: None.

P184

L199

Mean=55.5

[33–85] P184/L199 L89

NA

[0.1–4.3]

Agacayak, 2014 [75] Turkey Retr. CS CoI: NR

SoF: NR P88

Mean=47

[36–70] P88 P29 NR

Bernardi, 2012 [35] Italy Prosp. CS CoI: None.

SoF: None. P769

Mean=54.3

[22–86] P769 P365

NA

[0–>5]

Kibil, 2013 [77] Poland Retr. CS CoI: None.

SoF: NR P62

Mean=49.6

[18–76] P62 P12

0.8

[0.4–1.8]

Dialani, 2014 [82] USA Retr. CS CoI: NR

SoF: NR P37

Med.=50

[41–68] P37 P29

NA

[0.2–7]

Brennan, 2012 [83] USA Retr. CS CoI: NR

SoF: NR

P73/

L75

Mean=50

Med.=49

[27–70]

P73/L75 L67 0.4

[>0.1–0.9]

Rauch, 2012 [84] USA Retr. CS CoI: NR

SoF: NR P197/ L218

Mean=52

[28–76] P197/L218 L85

1

[0.5–3.6]

Heller, 2014 [85] USA, UK Retr. CS CoI: NR

SoF: NR P140/ L151

Med.=50

[26–84] P140/L151 L147 NR

Bianchi, 2012 [86] Italy Retr. CS

CoI: None.

SoF: „Ente Cassa di

Risparmio“.

P589 NA P589 P589 NR

Mariscotti, 2014 [42] Italy Retr. CS CoI: NR

SoF: NR L169

Mean=52.7 L82 L25 0.8

Mean=53.9 L87 L33 0.9

Venkataraman, 2012

[78] USA Retr. CS

CoI: NR

SoF: NR

P877/

L912

Mean=56.2

[31–88] L435 L185

0.9

[0.2–7]

Mean=55.4

[25–86] L393 L193

0.9

[0.2–6]

Kibil, 2012 [37] Poland Retr. CS CoI: NR

SoF: NR

P1177/

L1183

Mean=41.7

[18–92] P1177/L1183 L152

1.2

[0.4–6.5]

Timpe, 2015 [87] Germany Retr. CS CoI: NR P506 NR P506 P119 NR

57

SoF: NR

Lourenco, 2014 [88] USA Retr. CS CoI: NR

SoF: NR P96

Mean=52

[34–79] P96 P69

1.6

[0.4–6]

Schaefer, 2012 [79] Germany Prosp. CS CoI: NR

SoF: NR P178

Mean=52

[32–81] P178 0 NR

Parkin, 2014 [80] UK Retr. CS* CoI: None.

SoF: NR P70

Mean=55

[42–76]

P52 P11 NR

P55 P19

Legend: CoI – conflict of interest; CS – case series; Lsns. or L – lesions; M – man/men; Med. – median; NA – not applicable; No. – number; NR – not reported; Prosp. – prospective;

Pts. or P – patients; ref. – reference; Ref. stand. – reference standard; Retr. – retrospective; SoF – source of funding; UK – United Kingdom; USA – the United States of America; yrs.

– years.

*Only 11 VABB and 19 CNB patients were included.

58

Table III. Evidence table for case series study outcomes.

Author, years

[ref.]

Index test: VABB Reference stand.:

surgical excision Outcomes

Biopsy method

(No. of pts.)

Needle

size Final diagnosis Final diagnosis

Sensitivity

(%)

Specificity

(%)

PPV/

NPV

(%)

FN/ FP

(%)

Underestimation

rate (%) [No. of

pts./lsns.]

Debi, 2015

[76]

US-VABB

(Mammot)

(P40/P43)

S-VABB

(Mammot)

(P3/P43)

11G

IDC: 23/43;

ILC: 5/43;

DCIS: 1/43;

NHL: 1/43;

Met. LCa: 1/43;

Fibroadenoma: 8/43;

Fibrocystic disease: 2/43;

Mastitis: 1/43;

Abscess: 1/43.

IDC: 19/31;

ILC: 4/31;

DCIS: 2/31;

Met. LCa: 1/31;

Fibroadenoma: 4/31;

Abscess: 1/31.

100* 100 100/

100

0/31* (0)

0/31 (0) 0

Hawley, 2015

[81]

US-VABB

(L110/L199)

S-VABB

(L78/L199)

MRI-VABB

(L11/L199)

8G

(US);

9G;

10G;

11G;

12G;

13G.

Benign papilloma:

199/199.

DCIS: 4/89;

Papilloma w. atypia:

21/89;

Benign papilloma: 64/89.

0 100 0/

95.5

4/89 (4.5)

0/89 (0)

4.5

[US-VABB: 1;

S-VABB: 3;

MRI-VABB: 0]

Agacayak, 2014

[75]

S-VABB

(P88/P88) NR

Malignant: 25/88:

ICa: 5/25;

DCIS: 20/25;

ADH: 4/88;

Benign: 59/88.

Malignant: 25/29;

Benign: 4/29. 100* 100

100/

100

0/29* (0)

0/29 (0) 0

Bernardi, 2012

[35]

S-VABB

(Mammot)

(P769/P769)

11G

Invasive: 58/769;

In situ: 187/769;

High-risk: 142/769;

Benign: 319/769;

Normal: 63/769.

Invasive: 69/365;

In situ: 167/365;

Atypia: 52/365;

Benign: 77/365.

93.7 100 100/

87.6

16/365 (4.4)

0/365 (0)

4.4

[S-VABB: 16]

Kibil, 2013 [77]

US-VABB

(P44/P62)

S-VABB

(P18/P62)

(Mammot/

EnCor)

10G/

11G


12/62;

Papilloma w.out atypia:

50/62.

IDC: 1/12;

ILC: 1/12;

ALH: 2/12;

Benign: 8/12.

0 100 0/

83.3

2/12 (16.7)

0/12 (0)

16.7

[NR: 2]

Dialani, 2014

[82]

S-VABB

(P30/P37)

(Mammot/

ATEC)

8G/

9G FEA: 37/37.

DCIS: 1/29;

LCIS: 1/29;

ADH: 4/29;

ALH:14/29;

0 100 0/

93.1

2/29 (6.9)

0/29 (0)

6.9

[S-VABB: 2]

59

MRI-VABB

(P7/P37)

(VaCora/

ATEC)

9G/

10G

FEA: 15/29;

Benign: 7/29.

Brennan, 2012

[83]

MRI-VABB

(L75/L75)

(ATEC)

9G


25/75;


50/75.

DCIS: 4/67;

LCIS: 3/67;

ADH: 1/67;

ALH: 1/67;

Papilloma w.atypia:

1/67;


22/67;

Radial scar: 1/67;

Columnar cell changes

w. atypia: 1/67;

Benign: 20/67.

0 100 0/

94

4/67 (6)

0/67 (0)

6

[MRI-VABB: 4]

Rauch,

2012 [84]

MRI-VABB

(L218/L218)

(ATEC)

9G

Malignant: 48/218:

IDC: 6/48;

ILC: 8/48;

IDC+ILC: 6/48;

IDC+DCIS: 6/48;

DCIS: 22/48;

High-risk: 37/218:

ADH: 13/37;

ALH: 12/37;

LCIS: 6/37;

Radical scar: 6/37;

Benign: 133/218.

Malignant: 54/85:

IDC: 10/54;

ILC: 9/54;

IDC+ILC: 6/54;

DCIS: 22/54;

IDC+DCIS: 7/54;

High-risk 12/85;

Benign: 19/85.

88.9 100 100/ 83.8 6/85 (7.1)

0/85 (0)

7.1

[MRI-VABB: 6]

Heller,

2014 [85]

MRI-VABB

(L151/L151)

(ATEC)

9G

High-risk: 151/151:

LCIS: 30/151;

ADH: 35/151;

ALH: 15/151;

Papillary: 30/151;

FEA: 16/151;

Radial scar: 25/151.

Malignant: 30/147:

IDC: 9/30;

ILC: 2/30;

DCIS: 19/30;

High-risk: 78/147;

Benign: 39/147.

0 100 0/

79.6

30/147

(20.4)

0/147 (0)

20.4

[MRI-VABB: 30]

Bianchi, 2012

[86]

S-VABB

(P589/P589)

(Mammot)

11G

FEA+ADH+LIN:

34/589;

FEA+LIN: 90/589;

FEA+ADH: 275/589;

FEA: 190/589.

Malignant: 114/589;

High-risk: 308/589;

Benign: 167/589.

0 100 0/

80.6

114/589

(19.4)

0/589 (0)

19.4

[S-VABB: 114]

Mariscotti, 2014

[42]

S-VABB

(L82/L169)

(EnCor)

10G

Malignant: 12/82;

High-risk: 12/82;

Benign: 58/82.

Malignant: 12/25:

ICa: 3/12;

DCIS: 9/12;

Benign: 13/25.

100* 100 100/

100

0/25* (0)

0/25 (0)

0

[S-VABB: 0]

S-VABB

(L87/L169) 11G

Malignant: 18/82;

High-risk: 15/82;

Malignant: 19/33:

DCIS: 19/19; 94.7 100

100/

93.3

1/33 (3)

0/33 (0)

3

[S-VABB: 1]

60

(Mammot) Benign: 54/82. Benign: 14/33.

Venkataraman,

2012 [78]

S-VABB

(L435/L828)

(Mammot)

8G

Malignant: 97/435:

DCIS: 70/97;

ICa: 27/97;

High-risk: 84/435;

Benign: 254/435.

Malignant: 106/185:

ICa: 34/106;

DCIS: 72/106;

High-risk: 75/185;

Benign: 4/185.

91.5 100 100/

89.8

9/185 (4.9)

0/185 (0)

4.9

[S-VABB: 9]

S-VABB

(L393/L828)

(Mammot)

11G

Malignant: 107/393:

ICa: 30/107;

DCIS: 77/107;

High-risk: 69/393;

Benign: 217/393.

Malignant: 120/193:

ICa: 46/120;

DCIS: 74/120;

High-risk: 59/193;

Benign: 14/193.

89.2 100 100/

84.9

13/193 (6.7)

0/193 (0)

6.7

[S-VABB: 13]

Kibil,

2012 [37]

US-VABB

(L1183/L1183)

(EnCor/

Mammot)

10G/

11G

Malignant: 122/1183:

IDC: 114/122;

ILC: 4/122;

DCIS: 4/122;

High-risk: 30/1183:

AH: 25/30;

LCIS: 5/30;

Benign: 1025/1183;

Non-diagnostic: 6/1183.

Malignant: 124/152:

IDC: 117/124;

ILC: 4/124;

DCIS: 3/124;

High-risk: 8/152:

AH: 3/8;

LCIS: 5/8;

Benign: 20/152.

98.4 100 100/

93.3

2/152 (1.3)

0/152 (0)

1.3

[US-VABB: 2]

Timpe,

2015 [87] NA 9G

Malignant: 82/506:

ICa: 11/82;

DCIS: 71/82;

High-risk: 60/506;

Benign: 359/506;

NR: 5/506.

Malignant: 91/119:

ICa: 19/91;

DCIS: 72/91;

Benign: 28/119.

90.1 100 100/

75.7

9/119 (7.6)

0/119 (0)

7.6

[NA: 9]

Lourenco, 2014

[88]

MRI-VABB

(P96/P96)

(ATEC)

9G

High-risk: 96/96:

ADH: 20/96;

LN: 9/96;

Papillary lesion: 27/96;

Radial scar: 20/96;

Other atypia: 20/96.

Malignant: 16/69:

ICa: 5/16;

DCIS: 11/16;

High-risk: 53/69:

ADH: 13/53;

LN: 5/53;

Papillary lesion: 16/53;

Radial scar: 10/53;

Other atypia: 9/53.

0 100 0/

76.8

16/69 (23.2)

0/69 (0)

23.2

[MRI-VABB: 16]

Schaefer, 2012

[79]

S-VABB

(P115/P178)

(Mammot)

8G

Benign: 178/178. – – – – – –

11G

S-VABB

(P63/P178)

(ATEC)

9G

12G

Parkin, 2014 [80] US-VABB/

S-VABB

7G;

8G;

Malignant: 5/52:

ILC: 2/5;

Malignant: 6/11:

ILC: 2/6; 83.3 100

100/

83.3

1/11 (9.1)

0/11 (0)

9.1

[NR: 1]

61

(Mammot)

(P45/P52)

(EnCor)

(P2/P5)

(VaCora)

(P5/P52)

10G;

11G

DCIS: 3/5;

ADH: 2/52;

Benign: 45/52.

IDC: 1/6;

DCIS: 3/6;

ADH: 1/11;

Benign: 4/11.

CNB

(P55/P55) 14G Benign: 55/55.

Malignant: 8/19:

ILC: 4/8;

IDC: 1/8;

DCIS: 3/8;

ADH: 1/19;

Benign: 10/19.

0 100 0/

57.9

8/19 (42.1)

0/19 (0)

42.1

[NR: 8]

Legend: % – percent; ADH – atypical ductal hyperplasia; AH – atypical hyperplasia; ALH – atypical lobular hyperplasia; ATEC/ EnCor/ Mammot/ Vacora – manufacturers of

vacuum assisted biopsy; DCIS – ductal carcinoma in situ; FEA – flat epithelial atypia; FN – false negative; FP – false positive; G – gauge; ICa – invasive carcinoma; IDC –

infiltrating ductal carcinoma; ILC – infiltrating lobular carcinoma; LCa – lung cancer; LCIS – lobular carcinoma in situ; LN – lobular neoplasia; lsns. – lesions; Mammot –

Mammotome; Met. – metastasis; MRI-VABB – magntic resonance imaging-guided vacuum assisted biopsy; NA – not applicable; NHL – non-Hodgkin lymphoma; No. – number;

NPV – negative predictive value; NR – not reported; PPV – positive predictive value; pts. – patients; ref. – reference; S-VABB – stereotactic-guided vacuum assisted biopsy; US-

VABB – ultrasound-guided vacuum assisted biopsy; VABB – vacuum assisted breast biopsy; w. – with; w.out – without.

*Some study authors specifically stated that diagnoses of malignancy on VABB were assumed to be correct, whether or not a tumor was observed upon surgical excision. This

assessment also classified all diagnoses of malignancy on VABB as true positives.

62

Table IV. Evidence table for case series study details and outcomes (Clinical effectiveness domain – quality of life).

Study details Study population Quality of life and patient-related outcomes

Author,

years [ref.] Country

Study

design

CoI

SoF

No. of

pts./lsns.

(sex)

Age

[range yrs.]

Biopsy method

(No. of pts.)

Condition

Patient satisfaction Before

procedure

(mean)

During

procedure

(mean)

After

procedure

(mean)

Tagliacifo,

2015 [95] Italy

Prosp.

CS

CoI: None.

SoF: Uni. of

Genova,

AIRC.

P90 Mean=55.8

[40–87]

S-VABB (DBT)

(P45/P90)

Pain: 2.6;

Anxiety: 3.1.

Pain: 2.7;

Anxiety: 3.2;

Vasovagal r.:

4/45.

Physical f.: 2.4;

Mental f.: 3.1.

Overall satisf.: Med.=3 [2–4];

Embarrassment: Med.=3 [2–4].

S-VABB (MMx)

(P45/P90)

Pain: 2.5;

Anxiety: 3.0.

Pain: 2.6;

Anxiety: 3.0;

Vasovagal r.:

3/45.

Physical f.: 2.2;

Mental f.: 2.8.

Overall satisf.: Med.=3 [2–4];

Embarrassment: Med.=3 [2–3].

Eller,

2014 [55] Germany

Retr.

CS

CoI: NR

SoF: NR P189

Med.=61

[32–87]

(ATEC)

9G (P150/P189) NR Condition: 2.6. Condition: 2.2.

Complications: 62/150 (41.3%);

Satisf. cosmetic: 146/150 (97.3%);

Prefer again: 132/150 (88%).

(Mammot)

11G (P39/P189) NR Condition: 2.2. Condition: 1.8.

Complications: 7/39 (17.9%);

Satisf. cosmetic: 38/39 (97.4%);

Prefer again: 36/39 (92.3%).

Legend: AIRC – Associazione Italiana Ricerca sul Cancro IG; ATEC/ EnCor/ Mammot/ VaCora – manufacturers of vacuum assisted biopsy; CoI – conflict of interest; CS – case

series; DBT – digital breast tomosynthesis; f. – function; G – gauge; yrs. – years; lsns. or L – lesions; M – man/men; Med. – median; MMx – mammography; No. – number; NR –

not reported; Prosp. – prospective; Pts. or P – patients; r. – reaction; ref. – reference; Ref. stand. – reference standard; Retr. – retrospective; satisfy. – satisfaction; SoF – source of

funding; S-VABB – stereotactic-guided vacuum assisted biopsy; Uni. – university.

63

Table V. Evidence table for case series study outcomes (Safety domain – adverse events).

Author, years [ref.] Biopsy method

(No. of pts./lsns.) Needle size

Adverse events (No. of pts. and %)

Device and/or

Procedure related Serious Non-serious

Agacayak, 2014 [75] S-VABB

(P88/P88) NR – –

Haematoma: 1/88 (1.1);

Ecchymosis: 2/88 (2.3).

Kibil, 2013 [77]

US-VABB (P44/P62)

S-VABB (P18/P62)

(Mammot/ EnCor)

10G/11G – – Haematoma: 3/62 (4.8).

Eller, 2014 [55]

(ATEC)

(P150/P189) 9G – Infection: 0/150 (0). Haematoma: 62/145 (42.8).

(Mammot)

(P39/P189) 11G – Infection: 0/39 (0). Haematoma: 12/34 (35.3).

Mariscotti, 2014 [42]

S-VABB (L82/L169)

(EnCor) 10G

Intraoperative severe bleeding:

1/82 (1.2). – Haematoma: 4/82 (4.9).

S-VABB (L87/L169)

(Mammot) 11G – – Haematoma: 3/87 (3.4).

Venkataraman, 2012

[78]

S-VABB (L435/L828)

(Mammot) 8G – – –

S-VABB (L393/L828)

(Mammot) 11G

Intraoperative severe bleeding:

2/393 (0.5). – –

Kibil, 2012 [37] US-VABB (P1177/P1177)

(EnCor/ Mammot) 10G/11G –

Haematoma w. surgical

interv.: 1/1177 (0.1).

Haematoma: 194/1177 (16.5);

Skin ecchymosis w.out

haematoma: 224/1177 (19).

Schaefer, 2012 [79]

S-VABB

(P115/P178)

(Mammot)

8G

Intraoperative bleeding:

13/31 (41.9):

Small: 9/13 (69.2);

Mod.-severe: 4/13 (30.8).


Scar formation: 1/31 (3.2).

Haematoma: 9/31 (29);


11G


7/84 (8.3):

Small: 5/7 (71.4);

Mod.-severe: 2/7 (28.6).

Pain: 1/84 (1.2).



Haematoma: 13/84 (15.5);


S-VABB

(P63/P178)

(ATEC)

9G


7/26 (26.9):

Small: 7/7 (100);

Mod.-severe: 0/7 (0).

Haematoma: 5/26 (19.2);


Haematoma: 6/26 (23.1);


12G Intraoperative bleeding:

11/37 (29.7):


Scar formation: 0/37 (0).

Haematoma: 13/37 (35.1);


64

Small: 10/11 (90.9);

Mod.-severe: 1/11 (9.1).

Legend: % – percent; ATEC/ EnCor/ Mammot/ VaCora – manufacturers of vacuum assisted biopsy; G – gauge; interv. – intervention; lsns. or L – lesions; Mammot – Mammotome;

Mod. – moderate; MRI-VABB – magntic resonance imaging-guided vacuum assisted biopsy; No. – number; NR – not reported; pts. – patients; ref. – reference; S-VABB –

stereotactic-guided vacuum assisted biopsy; US-VABB – ultrasound-guided vacuum assisted biopsy; w. – with; w.out – without.

65

APPENDIX 5: QUALITY ASSESSMENT OF SELECTED STUDIES

Included studies

Case series

1. Parkin CK, Garewal S, Waugh P, Maxwell AJ. Outcomes of patients with lobular in situ neoplasia of the breast: the

role of vacuum-assisted biopsy. Breast. 2014 Oct;23(5):651-5.

2. Hawley JR, Lawther H, Erdal BS, Yildiz VO, Carkaci S. Outcomes of benign breast papillomas diagnosed at

image-guided vacuum-assisted core needle biopsy. Clinical Imaging. 2015 Jul-Aug;39(4):576-81.

3.

Agacayak F, Ozturk A, Bozdogan A, Selamoglu D, Alco G, Ordu C, Pilanci KN, Killi R, Ozmen V. Stereotactic

vacuum-assisted core biopsy results for non-palpable breast lesions. Asian Pacific Journal of Cancer Prevention.

2014;15(13):5171-4.

4.

Bernardi D, Borsato G, Pellegrini M, Tuttobene P, Fanto' C, Valentini M, Aldovini D, Ciatto S. On the diagnostic

accuracy of stereotactic vacuum-assisted biopsy of nonpalpable breast abnormalities. Results in a consecutive

series of 769 procedures performed at the Trento Department of Breast Diagnosis. Tumori. 2012 Jan-

Feb;98(1):113-8.

5. Kibil W, Hodorowicz-Zaniewska D, Popiela TJ, Kulig J. Vacuum-assisted core biopsy in diagnosis and treatment

of intraductal papillomas. Clinical Breast Cancer. 2013 Apr;13(2):129-32.

6. Dialani V, Venkataraman S, Frieling G, Schnitt SJ, Mehta TS. Does isolated flat epithelial atypia on vacuum-

assisted breast core biopsy require surgical excision? The Breast Journal. 2014 Nov-Dec;20(6):606-14.

7.

Brennan SB, Corben A, Liberman L, Dershaw DD, Brogi E, Van Zee KJ, Morris E. Papilloma diagnosed at MRI-

guided vacuum-assisted breast biopsy: is surgical excision still warranted? AJR. American Journal of

Roentgenology. 2012 Oct;199(4):W512-9.

8.

Tagliafico A, Gristina L, Bignotti B, Valdora F, Tosto S, Calabrese M. Effects on short-term quality of life of

vacuum-assisted breast biopsy: comparison between digital breast tomosynthesis and digital mammography. The

British Journal of Radiology. 2015;88(1056):20150593.

9. Eller A, Janka R, Lux M, Saake M, Schulz-Wendtland R, Uder M, Wenkel E. Stereotactic vacuum-assisted breast

biopsy (VABB)--a patients' survey. Anticancer Research. 2014 Jul;34(7):3831-7.

10. Rauch GM, Dogan BE, Smith TB, Liu P, Yang WT. Outcome analysis of 9-gauge MRI-guided vacuum-assisted

core needle breast biopsies. AJR. American Journal of Roentgenology. 2012 Feb;198(2):292-9.

11. Heller SL, Elias K, Gupta A, Greenwood HI, Mercado CL, Moy L. Outcome of high-risk lesions at MRI-guided 9-

gauge vacuum- assisted breast biopsy. AJR. American Journal of Roentgenology. 2014 Jan;202(1):237-45.

12.

Bianchi S, Bendinelli B, Castellano I, Piubello Q, Renne G, Cattani MG, Di Stefano D, Carrillo G, Laurino L,

Bersiga A, Giardina C, Dante S, Di Loreto C, Quero C, Antonacci CM, Palli D; VANCB Study Group.

Morphological parameters of flat epithelial atypia (FEA) in stereotactic vacuum-assisted needle core biopsies do

not predict the presence of malignancy on subsequent surgical excision. Virchows Archiv. 2012 Oct;461(4):405-17.

13.

Mariscotti G, Durando M, Robella M, Angelino F, Regini E, Campanino PP, Belletti M, Osano S, Bergamasco L,

Fonio P, Gandini G. Mammotome(®) and EnCor (®): comparison of two systems for stereotactic vacuum-assisted

core biopsy in the characterisation of suspicious mammographic microcalcifications alone. La Radiologia Medica.

2015 Apr;120(4):369-76.

14. Venkataraman S, Dialani V, Gilmore HL, Mehta TS. Stereotactic core biopsy: Comparison of 11 gauge with 8

gauge vacuum assisted breast biopsy. European Journal of Radiology. 2012 Oct;81(10):2613-9.

15. Kibil W, Hodorowicz-Zaniewska D, Kulig J. Mammotome biopsy under ultrasound control in the diagnostics and

treatment of nodular breast lesions – own experience. Polski Przeglad Chirurgiczny. 2012 May;84(5):242-6.

16.

Schaefer FK, Order BM, Eckmann-Scholz C, Strauss A, Hilpert F, Kroj K, Biernath-Wüpping J, Heller M, Jonat

W, Schaefer PJ. Interventional bleeding, hematoma and scar-formation after vacuum-biopsy under stereotactic

guidance: Mammotome(®)-system 11 g/8 g vs. ATEC(®)-system 12 g/9 g. European Journal of Radiology. 2012

May;81(5):e739-45.

17. Timpe L, Berkemeyer S, Puesken M, Tio J, Heindel W, Weigel S. Rates of presurgical underestimation of breast

cancer after standardized assessment of breast calcifications. RoFo. 2015 Jun;187(6):445-9.

18. Lourenco AP, Khalil H, Sanford M, Donegan L. High-risk lesions at MRI-guided breast biopsy: frequency and rate

of underestimation. AJR. American Journal of Roentgenology. 2014 Sep;203(3):682-6.

19.

Debi U, Thulkar S, Sharma S, Sharma MC, Seenu V, Deo SVS, Agarwal S, Hari S. Role of directional vacuum

assisted breast biopsy in previously equivocal biopsies for breast masses suspicious for malignancy. Malaysian

Journal of Pathology. 2015 Apr;37(1):25-33.

Systematic Reviews

1. Dahabreh IJ, Wieland LS, Adam GP, Halladay C, Lau J, Trikalinos TA. Core Needle and Open Surgical Biopsy for

Diagnosis of Breast Lesions: An Update to the 2009 Report. Comparative Effectiveness Review No. 139. (Prepared

66

by the Brown Evidence-based Practice Center under Contract 290-2012-00012-I.) AHRQ Publication No.14-

EHC040-EF. Rockville, MD: Agency for Healthcare Research and Quality. September 2014.

www.effectivehealthcare.ahrq.gov/reports/final.cfm

Excluded studies

Reference Exclusion

criteria

1.

Trentin C, Dominelli V, Maisonneuve P, Menna S, Bazolli B, Luini A, Cassano E. Predictors of

invasive breast cancer and lymph node involvement in ductal carcinoma in situ initially

diagnosed by vacuum-assisted breast biopsy: experience of 733 cases. Breast. 2012

Oct;21(5):635-40.

Wrong research

question.

2.

An Y, Kim S, Kang B, Lee J. Usefulness of magnetic resonance imaging-guided vacuum-

assisted breast biopsy in Korean women: a pilot study. World Journal of Surgical Oncology.

2013 Aug 16;11:200.

Wrong study

design.

3. Park HS, Jeon CW. Learning curve for breast mass excision using a vacuum-assisted biopsy

system. Minimally Invasive Therapy & Allied Technologies. 2014 Aug;23(4):235-40.

Wrong research

question.

4.

Yao F, Li J, Wan Y, Zhong Y, Wei W, Tu Y, Tong H, Sun S. Sonographically guided vacuum-

assisted breast biopsy for complete excision of presumed benign breast lesions. Journal of

Ultrasound in Medicine. 2012 Dec;31(12):1951-7.

Wrong

intervention.

5.

Shaylor SD, Heller SL, Melsaether AN, Gupta D, Gupta A, Babb J, Moy L. Short interval

follow-up after a benign concordant MR-guided vacuum assisted breast biopsy--is it

worthwhile? European Radiology. 2014 Jun;24(6):1176-85.

Wrong research

question.

6.

Nakano S, Otsuka M, Mibu A, Oinuma T. Significance of fine needle aspiration cytology and

vacuum-assisted core needle biopsy for small breast lesions. Clinical Breast Cancer. 2015

Feb;15(1):e23-6.

Wrong study

design.

7.

Choi ER, Han BK, Ko ES, Ko EY, Choi JS, Cho EY, Nam SJ. Initial Experience with a

Wireless Ultrasound-Guided Vacuum-Assisted Breast Biopsy Device. PLoS One. 2015 Dec

2;10(12):e0144046.

Wrong

intervention.

8.

Domeyer PJ, Sergentanis TN, Katsari V, Souliotis K, Mariolis A, Zagouri F, Zografos GC.

Screening in the era of economic crisis: misperceptions and misuse from a longitudinal study on

Greek women undergoing benign vacuum-assisted breast biopsy. Asian Pacific Journal of

Cancer Prevention. 2013;14(9):5023-9.

Wrong research

question.

9.

Strachan C, Horgan K, Millican-Slater RA, Shaaban AM, Sharma N. Outcome of a new patient

pathway for managing B3 breast lesions by vacuum-assisted biopsy: time to change current UK

practice? Journal of Clinical Pathology. 2016 Mar;69(3):248-54.

Wrong research

question.

10.

Sohn YM, Yoon JH, Kim EK, Moon HJ, Kim MJ. Percutaneous ultrasound-guided vacuum-

assisted removal versus surgery for breast lesions showing imaging-histology discordance after

ultrasound-guided core-needle biopsy. Korean Journal of Radiology. 2014 Nov-Dec;15(6):697-

703.

Wrong research

question.

11.

Imschweiler T, Haueisen H, Kampmann G, Rageth L, Seifert B, Rageth C, Freiwald B, Kubik-

Huch RA. MRI-guided vacuum-assisted breast biopsy: comparison with stereotactically guided

and ultrasound-guided techniques. European Radiology. 2014 Jan;24(1):128-35.

Incomplete

reporting of

results.

12.

Ferré R, Ianculescu V, Ciolovan L, Mathieu MC, Uzan C, Canale S, Delaloge S, Dromain C,

Balleyguier C. Diagnostic Performance of MR-guided Vacuum-Assisted Breast Biopsy: 8 Years

of Experience. The Breast Journal. 2016 Jan-Feb;22(1):83-9.

Incomplete

reporting of

results.

13.

Wang ZL, Liu G, Huang Y, Wan WB, Li JL. Percutaneous excisional biopsy of clinically

benign breast lesions with vacuum-assisted system: comparison of three devices. European

Journal of Radiology. 2012 Apr;81(4):725-30.

Wrong

intervention.

14.

Meroni S, Bozzini AC, Pruneri G, Moscovici OC, Maisonneuve P, Menna S, Penco S,

Meneghetti L, Renne G, Cassano E. Underestimation rate of lobular intraepithelial neoplasia in

vacuum-assisted breast biopsy. European Radiology. 2014 Jul;24(7):1651-8.

Wrong study

design.

15.

Mosier AD, Keylock J, Smith DV. Benign papillomas diagnosed on large-gauge vacuum-

assisted core needle biopsy which span <1.5 cm do not need surgical excision. The Breast

Journal. 2013 Nov-Dec;19(6):611-7.

Wrong

intervention.

16. Rajan S, Shaaban AM, Dall BJ, Sharma N. New patient pathway using vacuum-assisted biopsy

reduces diagnostic surgery for B3 lesions. Clinical Radiology. 2012 Mar;67(3):244-9.

Wrong research

question.

17. Gümüş H, Gümüş M, Devalia H, Mills P, Fish D, Jones P, Uyar A, Sever A. Causes of failure Wrong

http://www.effectivehealthcare.ahrq.gov/reports/final.cfm

67

in removing calcium in microcalcification-only lesions using 11-gauge stereotactic vacuum-

assisted breast biopsy. Diagnostic and Interventional Radiology. 2012 Jul-Aug;18(4):354-9.

intervention.

18.

Caplain A, Drouet Y, Peyron M, Peix M, Faure C, Chassagne-Clément C, Beurrier F,

Fondrevelle ME, Guérin N, Lasset C, Treilleux I. Management of patients diagnosed with

atypical ductal hyperplasia by vacuum-assisted core biopsy: a prospective assessment of the

guidelines used at our institution. American Journal of Surgery. 2014 Aug;208(2):260-7.

Wrong research

question.

19.

Schrading S, Distelmaier M, Dirrichs T, Detering S, Brolund L, Strobel K, Kuhl CK. Digital

breast tomosynthesis-guided vacuum-assisted breast biopsy: initial experiences and comparison

with prone stereotactic vacuum-assisted biopsy. Radiology. 2015 Mar;274(3):654-62.

Background.

20.

Tothova L, Rauova K, Valkovic L, Vanovcanova L, Lehotska V. Stereotactic vacuum-assisted

breast biopsy: our experience and comparison with stereotactic automated needle biopsy.

Bratislavke Lekarske Listy. 2013;114(2):71-7.

Incomplete

reporting of

results.

21.

Suh YJ, Kim MJ, Kim EK, Moon HJ, Kwak JY, Koo HR, Yoon JH. Comparison of the

underestimation rate in cases with ductal carcinoma in situ at ultrasound-guided core biopsy:

14-gauge automated core-needle biopsy vs 8- or 11-gauge vacuum-assisted biopsy. The British

Journal of Radiology. 2012 Aug;85(1016):e349-56.

Wrong

population.

22.

Bundred SM, Maxwell AJ, Morris J, Lim YY, Harake MJ, Whiteside S, Bundred NJ.

Randomized controlled trial of stereotactic 11-G vacuum-assisted core biopsy for the diagnosis

and management of mammographic microcalcification. The British Journal of Radiology.

2016;89(1058):20150504.

Background.

23.

Yamaguchi R, Tanaka M, Tse GM, Yamaguchi M, Terasaki H, Hirai Y, Nonaka Y, Morita M,

Yokoyama T, Kanomata N, Naito Y, Akiba J, Yano H. Management of breast papillary lesions

diagnosed in ultrasound-guided vacuum-assisted and core needle biopsies. Histopathology.

2015 Mar;66(4):565-76.

Incomplete

reporting of

results.

24.

Ohsumi S, Taira N, Takabatake D, Takashima S, Hara F, Takahashi M, Kiyoto S, Aogi K,

Nishimura R. Breast biopsy for mammographically detected nonpalpable lesions using a

vacuum-assisted biopsy device (Mammotome) and upright-type stereotactic mammography unit

without a digital imaging system: experience of 500 biopsies. Breast Cancer. 2014

Mar;21(2):123-7.

Background.

25.

Bahrs SD, Hattermann V, Preibsch H, Hahn M, Staebler A, Claussen CD, Siegmann-Luz KC.

MR imaging-guided vacuum-assisted breast biopsy: reduction of false-negative biopsies by

short-term control MRI 24-48 h after biopsy. Clinical Radiology. 2014 Jul;69(7):695-702.

Wrong research

question.

26.

Soumian S, Verghese ET, Booth M, Sharma N, Chaudhri S, Bradley S, Umranikar S, Millican-

Slater RA, Hanby AM, Francis A. Concordance between vacuum assisted biopsy and

postoperative histology: implications for the proposed Low Risk DCIS Trial (LORIS).

European Journal of Surgical Oncology. 2013 Dec;39(12):1337-40.

Wrong research

question.

27.

Order BM, Schaefer PJ, Peters G, Eckmann-Scholz C, Hilpert F, Strauss A, Warneke V,

Mathiak M, Heller M, Jonat W, Schaefer FK. Evaluation of two different vacuum-assisted

breast biopsy systems: Mammotome(R) system 11G/8G vs. ATEC(®) system 12G/9G. Acta

Radiologica. 2013 Mar 1;54(2):137-43.

Wrong research

question.

28.

Park HL, Min SY, Kwon SH, Song JY, Shin H, Nam SJ, Yang JH; KOREAN BREAST

CANCER SOCIETY MEMBERS. Nationwide survey of use of vacuum-assisted breast biopsy

in South Korea. Anticancer Research. 2012 Dec;32(12):5459-64.

Wrong research

question.

29.

Lacambra MD, Lam CC, Mendoza P, Chan SK, Yu AM, Tsang JY, Tan PH, Tse GM. Biopsy

sampling of breast lesions: comparison of core needle- and vacuum-assisted breast biopsies.

Breast Cancer Research and Treatment. 2012 Apr;132(3):917-23.

Incomplete

reporting of

results.

30.

Youk JH, Kim H, Kim EK, Son EJ, Kim MJ, Kim JA. Phyllodes tumor diagnosed after

ultrasound-guided vacuum-assisted excision: should it be followed by surgical excision?

Ultrasound in Medicine & Biology. 2015 Mar;41(3):741-7.

Wrong

population.

31.

Uematsu T, Kasami M, Takahashi K, Watanabe J, Yamasaki S, Tanaka K, Tadokoro Y, Ogiya

A. Clip placement after an 11-gauge vacuum-assisted stereotactic breast biopsy: correlation

between breast thickness and clip movement. Breast Cancer. 2012 Jan;19(1):30-6.

Wrong research

question.

32.

Myong JH, Kang BJ, Yoon SK, Kim SH, An YY. The clinical utility of a adding lateral

approach to conventional vertical approach for prone stereotactic vacuum-assisted breast

biopsy. Korean Journal of Radiology. 2013 Jul-Aug;14(4):568-75.

Wrong research

question.

33.

Uematsu T. Real-time virtual sonography (RVS)-guided vacuum-assisted breast biopsy for

lesions initially detected with breast MRI. Japanese Journal of Radiology. 2013

Dec;31(12):826-31.

Wrong study

design.

34. Hahn M, Krainick-Strobel U, Toellner T, Gissler J, Kluge S, Krapfl E, Peisker U, Duda V,

Degenhardt F, Sinn HP, Wallwiener D, Gruber IV; Minimally Invasive Breast Intervention Background.

68

Study Group (AG MiMi) of the German Society of Senology (DGS).; Study Group for Breast

Ultrasonography of the German Society for Ultrasound in Medicine (DEGUM).

Interdisciplinary consensus recommendations for the use of vacuum-assisted breast biopsy

under sonographic guidance: first update 2012. Ultraschall in der Medizin. 2012

Aug;33(4):366-71.

35.

Meeuwis C, Veltman J, van Hall HN, Mus RD, Boetes C, Barentsz JO, Mann RM. MR-guided

breast biopsy at 3T: diagnostic yield of large core needle biopsy compared with vacuum-

assisted biopsy. European Radiology. 2012 Feb;22(2):341-9.

Wrong

comparator.

36.

Dogan BE, Le-Petross CH, Stafford JR, Atkinson N, Whitman GJ. MRI-guided vacuum-

assisted breast biopsy performed at 3 T with a 9-gauge needle: preliminary experience. AJR.

American Journal of Roentgenology. 2012 Nov;199(5):W651-3.

Wrong

population.

37.

Viala J, Gignier P, Perret B, Hovasse C, Hovasse D, Chancelier-Galan MD, Bornet G,

Hamrouni A, Lasry JL, Convard JP. Stereotactic vacuum-assisted biopsies on a digital breast

3D-tomosynthesis system. The Breast Journal. 2013 Jan-Feb;19(1):4-9.

Wrong

intervention.

38.

El Khoury M, Mesurolle B, Omeroglu A, Aldis A, Kao E. Values of pathological analysis of

lost tissue fragments in the vacuum canister during a vacuum-assisted stereotactic biopsy of the

breast. The British Journal of Radiology. 2013 May;86(1025):20120270.

Wrong research

question.

39.

Youk JH, Kim MJ, Son EJ, Kwak JY, Kim EK. US-guided vacuum-assisted percutaneous

excision for management of benign papilloma without atypia diagnosed at US-guided 14-gauge

core needle biopsy. Annals of Surgical Oncology. 2012 Mar;19(3):922-8.

Wrong

intervention.

40. Yamaguchi T, Ojima N, Hayashi M, Komatsu N, Hashimoto S, Koyama M. Epidermal cyst of

the breast treated by vacuum-assisted biopsy. International Surgery. 2013 Jan-Mar;98(1):65-9.

Wrong study

design.

41.

Pistolese CA, Ciarrapico A, Perretta T, Cossu E, della Gatta F, Giura S, Caramanica C,

Simonetti G. Cost-effectiveness of two breast biopsy procedures: surgical biopsy versus

vacuum-assisted biopsy. La Radiologia Medica. 2012 Jun;117(4):539-57.

Wrong research

question.

42.

Taylor D, Kulawansa ST, McCallum DD, Saunders C. Peri-implant galactocele following

vacuum-assisted core biopsy of the breast: a cautionary tale. BMJ Case Reports. 2013 Jun

6;2013.

Wrong study

design.

43. Wyss P, Varga Z, Rössle M, Rageth CJ. Papillary lesions of the breast: outcomes of 156

patients managed without excisional biopsy. The Breast Journal. 2014 Jul-Aug;20(4):394-401.

Wrong

comparator.

44. Plantade R, Thomassin-Naggara I. MRI vacuum-assisted breast biopsies. Diagnostic and

Interventional Imaging. 2014 Sep;95(9):779-801. Background.

45.

Ko KH, Jung HK, Youk JH, Lee KP. Potential application of ultrasound-guided vacuum-

assisted excision (US-VAE) for well-selected intraductal papillomas of the breast: single-

institutional experiences. Annals of Surgical Oncology. 2012 Mar;19(3):908-13.

Wrong

intervention.

46.

Li S, Wu J, Chen K, Jia W, Jin L, Xiao Q, Zeng Y, Su F. Clinical outcomes of 1,578 Chinese

patients with breast benign diseases after ultrasound-guided vacuum-assisted excision:

recurrence and the risk factors. American Journal of Surgery. 2013 Jan;205(1):39-44.

Wrong

population.

47.

Bendifallah S, Defert S, Chabbert-Buffet N, Maurin N, Chopier J, Antoine M, Bezu C, Touche

D, Uzan S, Graesslin O, Rouzier R. Scoring to predict the possibility of upgrades to malignancy

in atypical ductal hyperplasia diagnosed by an 11-gauge vacuum-assisted biopsy device: an

external validation study. European Journal of Cancer. 2012 Jan;48(1):30-6.

Wrong research

question.

48.

Bianchi S, Bendinelli B, Castellano I, Piubello Q, Renne G, Cattani MG, Stefano DD, Carrillo

G, Laurino L, Bersiga A, Giardina C, Dante S, Loreto CD, Quero C, Antonacci CM, Palli D;

VANCB Study Group. Morphological parameters of lobular in situ neoplasia in stereotactic 11-

gauge vacuum-assisted needle core biopsy do not predict the presence of malignancy on

subsequent surgical excision. Histopathology. 2013 Jul;63(1):83-95.

Wrong

population.

49.

Bae S, Yoon JH, Moon HJ, Kim MJ, Kim EK. Breast Microcalcifications: Diagnostic Outcomes

According to Image-Guided Biopsy Method. Korean Journal of Radiology. 2015 Sep-

Oct;16(5):996-1005.

Incomplete

reporting of

results.

50.

Brennan SB. Breast magnetic resonance imaging for the interventionalist: magnetic resonance

imaging-guided vacuum-assisted breast biopsy. Techniques in Vascular and Interventional

Radiology. 2014 Mar;17(1):40-8.

Background.

51.

Kibil W, Hodorowicz-Zaniewska D, Popiela TJ, Szpor J, Kulig J. Mammotome biopsy in

diagnosing and treatment of intraductal papilloma of the breast. Polski Przeglad Chirurgiczny.

2013 Apr;85(4):210-5.

Incomplete

reporting of

results.

52.

Krammer J, Dutschke A, Kaiser CG, Schnitzer A, Gerhardt A, Radosa JC, Brade J, Schoenberg

SO, Wasser K. Impact of Tumor Localization and Method of Preoperative Biopsy on Sentinel

Lymph Node Mapping After Periareolar Nuclide Injection. PLoS One. 2016 Feb

11;11(2):e0149018.

Wrong research

question.

69

53.

Maxwell AJ, Mataka G, Pearson JM. Benign papilloma diagnosed on image-guided 14 G core

biopsy of the breast: effect of lesion type on likelihood of malignancy at excision. Clinical

Radiology. 2013 Apr;68(4):383-7.

Wrong

intervention.

54.

Xu Y, Ming J, Zhou Y, Qi X, Fan L, Jiang J. Mammotome-assisted endoscopic breast-

conserving surgery: a novel technique for early-stage breast cancer. World Journal of Surgical

Oncology. 2014 Apr 18;12:99.

Wrong study

design.

55. Lee CI, Wells CJ, Bassett LW. Cost minimization analysis of ultrasound-guided diagnostic

evaluation of probably benign breast lesions. The Breast Journal. 2013 Jan-Feb;19(1):41-8.

Wrong research

question.

56.

Yoon JH, Kim EK, Kwak JY, Moon HJ, Kim MJ. Is US-guided core needle biopsy (CNB)

enough in probably benign nodules with interval growth? Ultraschall in der Medizin. 2012

Dec;33(7):E145-50.

Wrong

intervention.

57.

Damron TA. Vacuum-assisted biopsy is useful for breast tissue, but how useful is it for soft-

tissue tumors in orthopaedics? Commentary on an article by Zarah Mohr, MD, et al.: "Vacuum-

assisted minimally invasive biopsy of soft-tissue tumors". The Journal of Bone & Joint Surgery.

American volume. 2012 Jan 18;94(2):e11.

Wrong study

design.

58.

Bitencourt AG, Cohen MP, Graziano L, Souza JA, Marques EF, Brites MR, Chojniak R.

Pseudoaneurysm after ultrasound-guided vacuum-assisted core breast biopsy. The Breast

Journal. 2012 Mar-Apr;18(2):177-8.

Wrong study

design.

59.

Kim J, Han W, Lee JW, You JM, Shin HC, Ahn SK, Moon HG, Cho N, Moon WK, Park IA,

Noh DY. Factors associated with upstaging from ductal carcinoma in situ following core needle

biopsy to invasive cancer in subsequent surgical excision. Breast. 2012 Oct;21(5):641-5.

Wrong research

question.

60.

Uematsu T, Takahashi K, Nishimura S, Watanabe J, Yamasaki S, Sugino T, Oishi T, Kakuda Y,

Sato M, Hayashi T. Real-time virtual sonography examination and biopsy for suspicious breast

lesions identified on MRI alone. European Radiology. 2016 Apr;26(4):1064-72.

Wrong

intervention.

61.

Sim YT, Litherland J, Lindsay E, Hendry P, Brauer K, Dobson H, Cordiner C, Gagliardi T,

Smart L. Upgrade of ductal carcinoma in situ on core biopsies to invasive disease at final

surgery: a retrospective review across the Scottish Breast Screening Programme. Clinical

Radiology. 2015 May;70(5):502-6.

Wrong research

question.

62.

Khoumais NA, Scaranelo AM, Moshonov H, Kulkarni SR, Miller N, McCready DR, Youngson

BJ, Crystal P, Done SJ. Incidence of breast cancer in patients with pure flat epithelial atypia

diagnosed at core-needle biopsy of the breast. Annals of Surgical Oncology. 2013

Jan;20(1):133-8.

Wrong research

question.

63.

Bianchi S, Bendinelli B, Saladino V, Vezzosi V, Brancato B, Nori J, Palli D. Non-malignant

breast papillary lesions - b3 diagnosed on ultrasound--guided 14-gauge needle core biopsy:

analysis of 114 cases from a single institution and review of the literature. Pathology Oncology

Research: POR. 2015 Jul;21(3):535-46.

Wrong

intervention.

64.

Destounis S, Seifert P, Somerville P, Murphy P, Morgan R, Arieno A, Young WL.

Underestimation of papillary breast lesions by core biopsy: correlation to surgical excision.

Breast Cancer. 2014 Mar;21(2):128-34.

Incomplete

reporting of

results.

65.

Murray MP, Luedtke C, Liberman L, Nehhozina T, Akram M, Brogi E. Classic lobular

carcinoma in situ and atypical lobular hyperplasia at percutaneous breast core biopsy: outcomes

of prospective excision. Cancer. 2013 Mar 1;119(5):1073-9.

Wrong research

question.

66.

Poole BB, Wecsler JS, Sheth P, Sener SF, Wang L, Larsen L, Tripathy D, Lang JE. Malignancy

rates after surgical excision of discordant breast biopsies. The Journal of Surgical Research.

2015 May 1;195(1):152-7.

Incomplete

reporting of

results.

67.

Villa A, Chiesa F, Massa T, Friedman D, Canavese G, Baccini P, Calabrese M, Tagliafico A.

Flat epithelial atypia: comparison between 9-gauge and 11-gauge devices. Clinical Breast

Cancer. 2013 Dec;13(6):450-4.

Wrong research

question.

68.

Sohn YM, Park SH. Comparison of sonographically guided core needle biopsy and excision in

breast papillomas: clinical and sonographic features predictive of malignancy. Journal of

Ultrasound in Medicine. 2013 Feb;32(2):303-11.

Wrong

intervention.

69.

Al-Harethee WA, Kalles V, Papapanagiotou I, Matiatou M, Georgiou G, Nonni A, Koulocheri

D, Liakou P, Theodoropoulos G, Zografos GC. Thermal damage of the specimen during breast

biopsy with the use of the Breast Lesion Excision System: does it affect diagnosis? Breast

Cancer. 2015 Jan;22(1):84-9.

Wrong research

question.

70.

Linebarger JH, Landercasper J, Ellis RL, Gundrum JD, Marcou KA, De Maiffe BM, Hudak JM,

Andersen JJ. Core needle biopsy rate for new cancer diagnosis in an interdisciplinary breast

center: evaluation of quality of care 2007-2008. Annals of Surgery. 2012 Jan;255(1):38-43.

Incomplete

reporting of

results.

71. Heil J, Kümmel S, Schaefgen B, Paepke S, Thomssen C, Rauch G, Ataseven B, Große R,

Dreesmann V, Kühn T, Loibl S, Blohmer JU, von Minckwitz G. Diagnosis of pathological

Wrong

population.

70

complete response to neoadjuvant chemotherapy in breast cancer by minimal invasive biopsy

techniques. British Journal of Cancer. 2015 Dec 1;113(11):1565-70.

72.

Kaplan JA, Grinstaff MW, Bloch BN. Polymer film-nanoparticle composites as new

multimodality, non-migrating breast biopsy markers. European Radiology. 2016

Mar;26(3):866-73.

Wrong

intervention.

73.

McLaughlin CT, Neal CH, Helvie MA. Is the upgrade rate of atypical ductal hyperplasia

diagnosed by core needle biopsy of calcifications different for digital and film-screen

mammography? AJR. American Journal of Roentgenology. 2014 Oct;203(4):917-22.

Wrong

intervention.

74.

Choi HY, Kim SM, Jang M, Yun BL, Kim SW, Kang E, Park SY, Moon WK, Ko ES. MRI-

guided intervention for breast lesions using the freehand technique in a 3.0-T closed-bore MRI

scanner: feasibility and initial results. Korean Journal of Radiology. 2013 Mar-Apr;14(2):171-8.

Wrong study

design.

75.

Szynglarewicz B, Kasprzak P, Halon A, Matkowski R. Preoperatively diagnosed ductal cancers

in situ of the breast presenting as even small masses are of high risk for the invasive cancer foci

in postoperative specimen. World Journal of Surgical Oncology. 2015 Jul 16;13:218.

Incomplete

reporting of

results.

76.

Arazi-Kleinman T, Skair-Levy M, Slonimsky E, Maly B, Uziely B, Libson E, Sella T.

JOURNAL CLUB: Is screening MRI indicated for women with a personal history of breast

cancer? Analysis based on biopsy results. AJR. American Journal of Roentgenology. 2013

Oct;201(4):919-27.

Wrong research

question.

77.

Gümüş H, Mills P, Gümüş M, Fish D, Jones S, Jones P, Devalia H, Sever A. Factors that impact

the upgrading of atypical ductal hyperplasia. Diagnostic and Interventional Radiology. 2013

Mar-Apr;19(2):91-6.

Wrong research

question.

78.

Kikuchi M, Tanino H, Kosaka Y, Sengoku N, Yamashita K, Minatani N, Nishimiya H, Waraya

M, Katoh H, Enomoto T, Kajita S, Woodhams R, Watanabe M. Usefulness of MRI of

microcalcification lesions to determine the indication for stereotactic mammotome biopsy.

Anticancer Research. 2014 Nov;34(11):6749-53.

Wrong

intervention.

79.

Oxner CR, Vora L, Yim J, Kruper L, Ellenhorn JD. Magnetic resonance imaging-guided breast

biopsy in lesions not visualized by mammogram or ultrasound. The American Surgeon. 2012

Oct;78(10):1087-90.

Only abstract

available.

80.

Kousaka J, Fujii K, Yorozuya K, Mouri Y, Yoshida M, Nakano S, Fukutomi T, Takahashi E,

Yokoi T. A case of quadruple primary malignancies including breast, tongue, and thyroid

cancers and osteosarcoma in a young female without karyotype abnormality. Breast Cancer.

2014 Jul;21(4):500-3.

Wrong study

design.

81.

Tunon-de-Lara C, Chauvet MP, Baranzelli MC, Baron M, Piquenot J, Le-Bouédec G, Penault-

Llorca F, Garbay JR, Blanchot J, Mollard J, Maisongrosse V, Mathoulin-Pélissier S,

MacGrogan G. The Role of Sentinel Lymph Node Biopsy and Factors Associated with Invasion

in Extensive DCIS of the Breast Treated by Mastectomy: The Cinnamome Prospective

Multicenter Study. Annals of Surgical Oncology. 2015 Nov;22(12):3853-60.

Wrong research

question.

82.

Nakahori R, Takahashi R, Akashi M, Tsutsui K, Harada S, Matsubayashi RN, Nakagawa S,

Momosaki S, Akagi Y. Breast carcinoma originating from a silicone granuloma: a case report.

World Journal of Surgical Oncology. 2015 Feb 22;13:72.

Wrong study

design.

83.

Gipponi M, Fregatti P, Garlaschi A, Calabrese M, Baccini P, Gallo M, Murelli F, Margarino C,

Bobbio C, Friedman D. Clinical decision-making in atypical and suspicious categories in fine-

needle aspiration cytology of the breast. Anticancer Research. 2015 Apr;35(4):2369-74.

Wrong

intervention.

84.

Lee SK, Yang JH, Woo SY, Lee JE, Nam SJ. Nomogram for predicting invasion in patients

with a preoperative diagnosis of ductal carcinoma in situ of the breast. The British Journal of

Surgery. 2013 Dec;100(13):1756-63.

Wrong research

question.

85.

Linda A, Zuiani C, Londero V, Di Gaetano E, Dal Col A, Girometti R, Bazzocchi M. Role of

magnetic resonance imaging in probably benign (BI-RADS category 3) microcalcifications of

the breast. La Radiologia Medica. 2014 Jun;119(6):393-9.

Wrong

intervention.

86. Tozaki M. BI-RADS-MRI terminology and evaluation of intraductal carcinoma and ductal

carcinoma in situ. Breast Cancer. 2013 Jan;20(1):13-20.

Wrong

intervention.

87.

Yamashita M, Ogawa T, Hanamura N, Kashikura Y, Mitsui T, Zhang X, Fujii K, Shiraishi T.

An uncommon case of T1b breast cancer with diabetic mastopathy in type II diabetes mellitus.

Breast Cancer. 2013 Jan;20(1):92-6.

Wrong study

design.

88. Uematsu T. How to choose needles and probes for ultrasonographically guided percutaneous

breast biopsy: a systematic approach. Breast Cancer. 2012 Jul;19(3):238-41. Background.

89.

Bianchi S, Giannotti E, Vanzi E, Marziali M, Abdulcadir D, Boeri C, Livi L, Orzalesi L,

Sanchez LJ, Susini T, Vezzosi V, Nori J. Radial scar without associated atypical epithelial

proliferation on image-guided 14-gauge needle core biopsy: analysis of 49 cases from a single-

centre and review of the literature. Breast. 2012 Apr;21(2):159-64.

Wrong research

question.

71

90.

Al Hassan T, Delli Fraine P, El-Khoury M, Joseph L, Zheng J, Mesurolle B. Accuracy of

percutaneous core needle biopsy in diagnosing papillary breast lesions and potential impact of

sonographic features on their management. Journal of Clinical Ultrasound: JCU. 2013

Jan;41(1):1-9.

Wrong study

design.

91.

Huang ML, Adrada BE, Candelaria R, Thames D, Dawson D, Yang WT. Stereotactic breast

biopsy: pitfalls and pearls. Techniques in Vascular and Interventional Radiology. 2014

Mar;17(1):32-9.

Background.

92.

Londero V, Zuiani C, Linda A, Girometti R, Bazzocchi M, Sardanelli F. High-risk breast

lesions at imaging-guided needle biopsy: usefulness of MRI for treatment decision. AJR.

American Journal of Roentgenology. 2012 Aug;199(2):W240-50.

Incomplete

reporting of

results.

93.

Kalles V, Zografos GC, Provatopoulou X, Kalogera E, Liakou P, Georgiou G, Sagkriotis A,

Nonni A, Gounaris A. Circulating levels of endothelin-1 (ET-1) and its precursor (Big ET-1) in

breast cancer early diagnosis. Tumour Biology. 2012 Aug;33(4):1231-6.

Wrong research

question.

94. Siegmann-Luz KC, Bahrs SD, Preibsch H, Hattermann V, Claussen CD. Management of breast

lesions detectable only on MRI. RoFo. 2014 Jan;186(1):30-6. Background.

95.

Becker AK, Gordon PB, Harrison DA, Hassell PR, Hayes MM, van Niekerk D, Wilson CM.

Flat ductal intraepithelial neoplasia 1A diagnosed at stereotactic core needle biopsy: is

excisional biopsy indicated? AJR. American Journal of Roentgenology. 2013 Mar;200(3):682-

8.

Incomplete

reporting of

results.

96. Kuerer HM. Ductal carcinoma in situ: treatment or active surveillance? Expert Review of

Anticancer Therapy. 2015;15(7):777-85. Background.

97.

Elshof LE, Tryfonidis K, Slaets L, van Leeuwen-Stok AE, Skinner VP, Dif N, Pijnappel RM,

Bijker N, Rutgers EJ, Wesseling J. Feasibility of a prospective, randomised, open-label,

international multicentre, phase III, non-inferiority trial to assess the safety of active

surveillance for low risk ductal carcinoma in situ - The LORD study. European Journal of

Cancer. 2015 Aug;51(12):1497-510.

Wrong study

design.

98.

Cheung YC, Juan YH, Ueng SH, Lo YF, Huang PC, Lin YC, Chen SC. Assessment of Breast

Specimens With or Without Calcifications in Diagnosing Malignant and Atypia for

Mammographic Breast Microcalcifications Without Mass: A STARD-Compliant Diagnostic

Accuracy Article. Medicine (Baltimore). 2015 Oct;94(42):e1832.

Wrong research

question.

99.

Brnic D, Brnic D, Simundic I, Vanjaka Rogosic L, Tadic T. MRI and comparison

mammography: a worthy diagnostic alliance for breast microcalcifications? Acta Radiologica.

2016 Apr;57(4):413-21.

Wrong

intervention.

100.

Okubo M, Tada K, Niwa T, Nishioka K, Tsuji E, Ogawa T, Seto Y. A case of breast cancer in

the axillary tail of Spence - enhanced magnetic resonance imaging and positron emission

tomography for diagnostic differentiation and preoperative treatment decision. World Journal of

Surgical Oncology. 2013 Sep 3;11:217.

Wrong study

design.

101.

Bendifallah S, Chabbert-Buffet N, Maurin N, Chopier J, Antoine M, Bezu C, Uzan S, Rouzier

R. Predictive factors for breast cancer in patients diagnosed with ductal intraepithelial neoplasia,

grade 1B. Anticancer Research. 2012 Aug;32(8):3571-9.

Wrong research

question.

102.

Kim GR, Kang J, Kwak JY, Chang JH, Kim SI, Youk JH, Moon HJ, Kim MJ, Kim EK.

Photoacoustic imaging of breast microcalcifications: a preliminary study with 8-gauge core-

biopsied breast specimens. PLoS One. 2014 Aug 25;9(8):e105878.

Wrong

intervention.

103.

Miyake T, Nakayama T, Naoi Y, Yamamoto N, Otani Y, Kim SJ, Shimazu K, Shimomura A,

Maruyama N, Tamaki Y, Noguchi S. GSTP1 expression predicts poor pathological complete

response to neoadjuvant chemotherapy in ER-negative breast cancer. Cancer Science. 2012

May;103(5):913-20.

Wrong research

question.

104.

Seror JY, Lesieur B, Scheuer-Niro B, Zerat L, Rouzier R, Uzan S. Predictive factors for

complete excision and underestimation of one-pass en bloc excision of non-palpable breast

lesions with the Intact(®) breast lesion excision system. European Journal of Radiology. 2012

Apr;81(4):719-24.

Wrong

intervention.

105.

Jung HJ, Hahn SY, Choi HY, Park SH, Park HK. Breast sonographic elastography using an

advanced breast tissue-specific imaging preset: initial clinical results. Journal of Ultrasound in

Medicine. 2012 Feb;31(2):273-80.

Wrong

intervention.

106. Wang ZL, Li N, Li M, Wan WB. Non-mass-like lesions on breast ultrasound: classification and

correlation with histology. La Radiologia Medica. 2015 Oct;120(10):905-10.

Wrong

intervention.

107. Hayashi H, Ohtani H, Yamaguchi J, Shimokawa I. Malignant transformation of breast ductal

adenoma: a diagnostic pitfall. The Malaysian Journal of Pathology. 2015 Dec;37(3):281-5.

Wrong study

design.

108. Jiang Y, Lou J, Wang S, Zhao Y, Wang C, Wang D. Evaluation of the role of dynamic contrast-

enhanced MR imaging for patients with BI-RADS 3-4 microcalcifications. PLoS One. 2014 Jun

Wrong

intervention.

72

13;9(6):e99669.

109.

Blum KS, Rubbert C, Mathys B, Antoch G, Mohrmann S, Obenauer S. Use of contrast-

enhanced spectral mammography for intramammary cancer staging: preliminary results.

Academic Radiology. 2014 Nov;21(11):1363-9.

Wrong study

design.

110. Rhee SJ, Ryu JK, Kim JH, Lim SJ. Nodular fasciitis of the breast: two cases with a review of

imaging findings. Clinical Imaging. 2014 Sep-Oct;38(5):730-3.

Wrong study

design.

111.

Kim SJ, Park YM, Jung SJ, Lee KH, Kim OH, Ryu JH, Choi GB, Lee SJ, Choo HJ, Jeong HW.

Sonographic appearances of juvenile fibroadenoma of the breast. Journal of Ultrasound in

Medicine. 2014 Nov;33(11):1879-84.

Wrong

intervention.

112.

Cupido BD, Vawda F, Sabri A, Sikwila CT. Evaluation and correlation of mammographically

suspicious lesions with histopathology at Addington Hospital, Durban. South African Medical

Journal. 2013 Mar 4;103(4):251-4.

Wrong

intervention.

113.

Ko KH, Jung HK, Kim SJ, Kim H, Yoon JH. Potential role of shear-wave ultrasound

elastography for the differential diagnosis of breast non-mass lesions: preliminary report.

European Radiology. 2014 Feb;24(2):305-11.

Wrong

intervention.

114.

de Groot JS, Moelans CB, Elias SG, Hennink A, Verolme B, Suijkerbuijk KP, Jager A,

Seynaeve C, Bos P, Witkamp AJ, Ausems MG, van Diest PJ, van der Wall E. Repeated nipple

fluid aspiration: compliance and feasibility results from a prospective multicenter study. PLoS

One. 2015 May 22;10(5):e0127895.

Wrong

intervention.

115.

Gautier N, Lalonde L, Tran-Thanh D, El Khoury M, David J, Labelle M, Patocskai E, Trop I.

Chronic granulomatous mastitis: Imaging, pathology and management. European Journal of

Radiology. 2013 Apr;82(4):e165-75.

Wrong

population.

116.

Ferris-James DM, Iuanow E, Mehta TS, Shaheen RM, Slanetz PJ. Imaging approaches to

diagnosis and management of common ductal abnormalities. Radiographics. 2012 Jul-

Aug;32(4):1009-30.

Background.

117.

Fiaschetti V, Salimbeni C, Gaspari E, Dembele GK, Bolacchi F, Cossu E, Pistolese CA, Perretta

T, Simonetti G. The role of second-look ultrasound of BIRADS-3 mammary lesions detected by

breast MR imaging. European Journal of Radiology. 2012 Nov;81(11):3178-84.

Wrong research

question.

118.

Hennigs A, Heil J. Diagnosis of pathological complete response by vacuum-assisted minimal

invasive biopsy after neoadjuvant chemotherapy in breast cancer – Results from a prospective

pilot study. Cancer Research. 2016 Feb;76(4) SUPPL. 1.

Wrong

population.

119.

Maxwell AJ, Bundred NJ, Harvey J, Hunt R, Morris J, Lim YY. A randomised pilot study

comparing 13 G vacuum-assisted biopsy and conventional 14 G core needle biopsy of axillary

lymph nodes in women with breast cancer. Clinical Radiology. 2016 Jun;71(6):551-7.

Wrong

population.

120.

Elshof LE, Tryfonidis K, Slaets L, Leeuwen-Stok AE, Dif N, Skinner VP, Loo CE, Warnars G,

Bleiker E, Pijnappel RM, Bijker N, Rutgers EJTh, Wesseling J. The LORD trial: A randomized,

non-inferiority trial, between active surveillance versus standard treatment in patients with low

risk ductal carcinoma in situ. Cancer Research. 2015 May;75(9) SUPPL. 1

Wrong

intervention.

121.

Taylor-Phillips S, Wallis MG, Duncan A, Gale AG. Use of prior mammograms in the transition

to digital mammography: a performance and cost analysis. European Journal of Radiology.

2012 Jan;81(1):60-5.

Wrong research

question.

122.

Taffurelli M, Pellegrini A, Ghignone F, Santini D, Zanotti S, Serra M. Positive predictive value

of breast lesions of uncertain malignant potential (B3): Can we identify high risk patients? The

value of a multidisciplinary team and implications in the surgical treatment. Surgical Oncology.

2016 Jun;25(2):119-22.

Incomplete

reporting of

results.

123.

Brancato B, Crocetti E, Bianchi S, Catarzi S, Risso GG, Bulgaresi P, Piscioli F, Scialpi M,

Ciatto S, Houssami N. Accuracy of needle biopsy of breast lesions visible on ultrasound: audit

of fine needle versus core needle biopsy in 3233 consecutive samplings with ascertained

outcomes. Breast. 2012 Aug;21(4):449-54.

Wrong

intervention.

124.

Gruber R, Jaromi S, Rudas M, Pfarl G, Riedl CC, Flöry D, Graf O, Sickles EA, Helbich TH.

Histologic work-up of non-palpable breast lesions classified as probably benign at initial

mammography and/or ultrasound (BI-RADS category 3). European Journal of Radiology. 2013

Mar;82(3):398-403.

Incomplete

reporting of

results.

125.

Chou CP, Wang YC, Chang SJ, Liu PH, Kuo SM. Evaluation of the Effects of Chitosan

Hemostasis Dressings on Hemorrhage Caused by Breast Biopsy. Breast Care (Basel). 2012

Jun;7(3):220-4.

Wrong

intervention.

126.

Lovrics P, Hodgson N, O'Brien MA, Thabane L, Cornacchi S, Coates A, Heller B, Reid S,

Sanders K, Simunovic M. The implementation of a surgeon-directed quality improvement

strategy in breast cancer surgery. American Journal of Surgery. 2013 Nov 8.

Wrong

intervention.

https://www.ncbi.nlm.nih.gov/pubmed/?term=Catarzi%20S%5BAuthor%5D&cauthor=true&cauthor_uid=22088803

https://www.ncbi.nlm.nih.gov/pubmed/?term=Risso%20GG%5BAuthor%5D&cauthor=true&cauthor_uid=22088803

https://www.ncbi.nlm.nih.gov/pubmed/?term=Bulgaresi%20P%5BAuthor%5D&cauthor=true&cauthor_uid=22088803

https://www.ncbi.nlm.nih.gov/pubmed/?term=Piscioli%20F%5BAuthor%5D&cauthor=true&cauthor_uid=22088803

https://www.ncbi.nlm.nih.gov/pubmed/?term=Scialpi%20M%5BAuthor%5D&cauthor=true&cauthor_uid=22088803

https://www.ncbi.nlm.nih.gov/pubmed/?term=Ciatto%20S%5BAuthor%5D&cauthor=true&cauthor_uid=22088803

https://www.ncbi.nlm.nih.gov/pubmed/?term=Houssami%20N%5BAuthor%5D&cauthor=true&cauthor_uid=22088803

https://www.ncbi.nlm.nih.gov/pubmed/?term=Pfarl%20G%5BAuthor%5D&cauthor=true&cauthor_uid=22429299

https://www.ncbi.nlm.nih.gov/pubmed/?term=Riedl%20CC%5BAuthor%5D&cauthor=true&cauthor_uid=22429299

https://www.ncbi.nlm.nih.gov/pubmed/?term=Fl%C3%B6ry%20D%5BAuthor%5D&cauthor=true&cauthor_uid=22429299

https://www.ncbi.nlm.nih.gov/pubmed/?term=Graf%20O%5BAuthor%5D&cauthor=true&cauthor_uid=22429299

https://www.ncbi.nlm.nih.gov/pubmed/?term=Sickles%20EA%5BAuthor%5D&cauthor=true&cauthor_uid=22429299

https://www.ncbi.nlm.nih.gov/pubmed/?term=Helbich%20TH%5BAuthor%5D&cauthor=true&cauthor_uid=22429299

https://www.ncbi.nlm.nih.gov/pubmed/?term=Thabane%20L%5BAuthor%5D&cauthor=true&cauthor_uid=24315382

https://www.ncbi.nlm.nih.gov/pubmed/?term=Cornacchi%20S%5BAuthor%5D&cauthor=true&cauthor_uid=24315382

https://www.ncbi.nlm.nih.gov/pubmed/?term=Coates%20A%5BAuthor%5D&cauthor=true&cauthor_uid=24315382

https://www.ncbi.nlm.nih.gov/pubmed/?term=Heller%20B%5BAuthor%5D&cauthor=true&cauthor_uid=24315382

https://www.ncbi.nlm.nih.gov/pubmed/?term=Reid%20S%5BAuthor%5D&cauthor=true&cauthor_uid=24315382

https://www.ncbi.nlm.nih.gov/pubmed/?term=Sanders%20K%5BAuthor%5D&cauthor=true&cauthor_uid=24315382

https://www.ncbi.nlm.nih.gov/pubmed/?term=Simunovic%20M%5BAuthor%5D&cauthor=true&cauthor_uid=24315382

73

127. Michalopoulos NV, Maniou I, Zografos GC. Breast lesion excision system biopsy: the learning

curve. AJR Americal Journal of Roentgenology. 2012 Nov;199(5):W667.

Wrong study

design.

128.

Park ER, Traeger L, Willett J, Gerade B, Webster A, Rastegar S, Denninger JW, Lee JM. A

relaxation response training for women undergoing breast biopsy: exploring integrated care.

Breast. 2013 Oct;22(5):799-805.

Wrong

intervention.

74

Quality assessment

Table VI. Quality assessment of the selected case series regarding risk of bias and applicability concerns.

Study

RISK OF BIAS APPLICABILITY CONCERNS

PATIENT

SELECTION INDEX TEST REFERENCE

STANDARD

FLOW AND

TIMING

PATIENT

SELECTION INDEX

TEST

REFERENCE

STANDARD

Debi, 2015 [76] Unclear Low Unclear High Low Low Low

Parkin, 2014 [80] Unclear Low Unclear Unclear Low Low Low

Hawley, 2015 [81] Low Low Unclear Unclear Low Low Low

Agacayak, 2014 [75] Unclear Low Unclear Unclear Low Low Low

Bernardi, 2012 [35] Low Low Unclear High Low Low Low

Kibil, 2013 [77] Low Low Unclear Unclear Low Low Low

Dialani, 2014 [82] Low Low Low High Low Low Low

Brennan, 2012 [83] Low Low Unclear High Low Low Low

Rauch, 2012 [84] Unclear Low Unclear Unclear Low Low Low

Heller, 2014 [85] Low Low Unclear Unclear Low Low Low

Bianchi, 2012 [86] Unclear Low Unclear Low Low Low Low

Mariscotti, 2014 [42] Low Low Unclear Unclear Low Low Low

Venkataraman, 2012 [78] Low Low Unclear High Low Low Low

Kibil, 2012 [37] Unclear Low Unclear High Low Low Low

Timpe, 2015 [87] Low Low Unclear High Low Low Low

Lourenco, 2014 [88] Low Low Unclear High Low Low Low

75

Table VII. Quality assessment of the selected systematic review.

Dahabreh, 2014 [89]

1.Was an ‘a priori’ design provided? Yes

2.Was there duplicate study selection and data extraction? Yes

3.Was a comprehensive literature search performed? Yes

4.Was a status of publication (i.e., grey literature) used as an inclusion

criterion? No

5.Was a list of studies (included and excluded) provided? Yes

6.Were the characteristics of the included studies provided? Yes

7.Was the scientific quality of the included studies assessed and

documented? Yes

8.Was the scientific quality of the included studies used appropriately in

formulating conclusions? Yes

9.Were the methods used to combine the findings of studies appropriate? Yes

10.Was the likelihood of publication bias assessed? Yes

11.Was the conflict of interest included? Yes

76

Table VIII. Quality appraisal checklist for case series included in Safety (AEs) and Clinical

effectiveness domains (QoL).

Schaefer, 2012 [79] Tagliafico, 2015 [95] Eller, 2014 [55]

Study objective

1. Was the hypothesis/ aim/

objective of the study clearly

stated?

Yes Yes Yes

Study design

2. Was the study conducted

prospectively? Yes Yes No

3. Were the cases collected in

more than one centre? Unclear No Unclear

4. Were patients recruited

consecutively? Yes Yes Yes

Study population

5. Were the characteristics of the

patients included in the study

described?

Yes Yes Yes

6. Were the eligibility criteria (i.e.

inclusion and exclusion

criteria) for entry into the study

clearly stated?

Yes Yes Yes

7. Did patients enter the study at a

similar point in the disease? Yes No Yes

Intervention and co-intervention

8. Was the intervention of interest

clearly described? Yes Partial Yes

9. Were additional interventions

(co-interventions) clearly

described?

Yes Yes Yes

Outcome measure

10. Were relevant outcome

measures established a priori? Yes Yes Yes

11. Were outcome assessors

blinded to the intervention that

patients received?

Unclear Yes Unclear

12. Were the relevant outcomes

measured using appropriate

objective/subjective methods?

Yes Partial No

13. Were the relevant outcome

measures made before and after

the intervention?

Yes Yes Yes

Statistical analysis

14. Were the statistical tests used

to assess the relevant outcomes

appropriate?

Yes Yes No

77

Results and conclusions

15. Was follow-up long enough for

important events and outcomes

to occur?

Yes Unclear Yes

16. Were losses to follow-up

reported? Yes Yes Yes

17. Did the study provided

estimates of random variability

in the data analysis of relevant

outcomes?

No Yes No

18. Were the adverse events

reported? Yes No Yes

19. Were the conclusions of the

study supported by results? Yes Yes Yes

Competing interests and sources of support

20. Were both competing interests

and sources of support for the

study reported?

No Yes No

Yes: 16/20

Unclear/Partial: 2/20

No: 2/20

Yes: 14/20


No: 3/20

Yes: 13/20


No: 5/20

78

QUADAS-2 checklist for case series

Phase 1: State the review question:

Patients (setting, intended use of index test, presentation, prior testing):

Phase 2: Draw a flow diagram for the primary study

Phase 3: Risk of bias and applicability judgments

QUADAS-2 is structured so that 4 key domains are each rated in terms of the risk of bias and the

concern regarding applicability to the research question (as defined above). Each key domain

has a set of signalling questions to help reach the judgments regarding bias and applicability.

DOMAIN 1: PATIENT SELECTION

A. Risk of Bias

Describe methods of patient selection:

❖ Was a consecutive or random sample of patients enrolled? Yes/No/Unclear

❖ Was a case-control design avoided? Yes/No/Unclear

❖ Did the study avoid inappropriate exclusions? Yes/No/Unclear

Could the selection of patients have introduced bias?RISK: LOW/HIGH/UNCLEAR

B. Concerns regarding applicability

Describe included patients (prior testing, presentation, intended use of index test and setting):

Is there concern that the included patients do not match the review question?

CONCERN: LOW/HIGH/UNCLEAR

DOMAIN 2: INDEX TEST(S)

If more than one index test was used, please complete for each test.

A. Risk of Bias

Describe the index test and how it was conducted and interpreted:

Were the index test results interpreted without knowledge of the results of the reference standard?

Yes/No/Unclear

If a threshold was used, was it pre-specified? Yes/No/Unclear

Could the conduct or interpretation of the index test have introduced bias? RISK: LOW

/HIGH/UNCLEAR


Is there concern that the index test, its conduct, or interpretation differ from the review

question? CONCERN: LOW /HIGH/UNCLEAR

79

DOMAIN 3: REFERENCE STANDARD

If more than one index test was used, please complete for each test.

A. Risk of Bias

Describe the reference standard and how it was conducted and interpreted:

Is the reference standard likely to correctly classify the target condition? Yes/No/Unclear

Were the reference standard results interpreted without knowledge of the results of the index test?

Yes/No/Unclear

Could the reference Standard, its conduct, or its interpretation have introduced bias?

RISK: LOW /HIGH/UNCLEAR


Is there concern that the target condition as defined by the reference standard does not match

the review question? CONCERN: LOW /HIGH/UNCLEAR

DOMAIN 4: FLOW AND TIMING

A. Risk of Bias

Describe any patients who did not receive the index test(s) and/or reference standard or who were

excluded from the 2x2 table (refer to flow diagram):

Describe the time interval and any interventions between index test(s) and reference Standard:

Was there an appropriate interval between index test(s) and reference standard? Yes/No/Unclear

Did all patients receive a reference standard? Yes/No/Unclear

Did patients receive the same reference standard? Yes/No/Unclear

Were all patients included in the analysis? Yes/No/Unclear

Could the patient flow have introduced bias? RISK: LOW /HIGH/UNCLEAR

80

The AMSTAR checklist for systematic reviews

1. Was an 'a priori' design provided?

The research question and inclusion criteria should be established before the conduct of the review.

Note: Need to refer to a protocol, ethics approval, or pre-determined/a priori published research objectives to score a

“yes.”

□ Yes

□ No

□ Can't answer

□ Not applicable

2. Was there duplicate study selection and data extraction?

There should be at least two independent data extractors and a consensus procedure for disagreements should be in

place.

Note: 2 people do study selection, 2 people do data extraction, consensus process or one person checks the other’s

work.

□ Yes

□ No

□ Can't answer

□ Not applicable

3. Was a comprehensive literature search performed?

At least two electronic sources should be searched. The report must include years and databases used (e.g., Central,

EMBASE, and MEDLINE). Key words and/or MESH terms must be stated and where feasible the search strategy

should be provided. All searches should be supplemented by consulting current contents, reviews, textbooks,

specialized registers, or experts in the particular field of study, and by reviewing the references in the studies found.

Note: If at least 2 sources + one supplementary strategy used, select “yes” (Cochrane register/Central counts as 2

sources; a grey literature search counts as supplementary).

□ Yes

□ No

□ Can't answer

□ Not applicable

4. Was the status of publication (i.e. grey literature) used as an inclusion

criterion?

The authors should state that they searched for reports regardless of their publication type. The authors should state

whether or not they excluded any reports (from the systematic review), based on their publication status, language etc.

Note: If review indicates that there was a search for “grey literature” or “unpublished literature,” indicate “yes.”

SIGLE database, dissertations, conference proceedings, and trial registries are all considered grey for this purpose. If

searching a source that contains both grey and non-grey, must specify that they were searching for grey/unpublished lit.

□ Yes

□ No

□ Can't answer

□ Not applicable

5. Was a list of studies (included and excluded) provided?

A list of included and excluded studies should be provided.

Note: Acceptable if the excluded studies are referenced. If there is an electronic link to the list but the link is dead,

select “no.”

□ Yes

□ No

□ Can't answer

□ Not applicable

6. Were the characteristics of the included studies provided?

In an aggregated form such as a table, data from the original studies should be provided on the participants,

interventions and outcomes. The ranges of characteristics in all the studies analyzed e.g., age, race, sex, relevant

socioeconomic data, disease status, duration, severity, or other diseases should be reported.

Note: Acceptable if not in table format as long as they are described as above.

□ Yes

□ No

81

□ Can't answer

□ Not applicable

7. Was the scientific quality of the included studies assessed and documented?

'A priori' methods of assessment should be provided (e.g., for effectiveness studies if the author(s) chose to include only

randomized, double-blind, placebo controlled studies, or allocation concealment as inclusion criteria); for other types of

studies alternative items will be relevant.

Note: Can include use of a quality scoring tool or checklist, e.g., Jadad scale, risk of bias, sensitivity analysis, etc., or a

description of quality items, with some kind of result for EACH study (“low” or “high” is fine, as long as it is clear

which studies scored “low” and which scored “high”; a summary score/range for all studies is not acceptable).

□ Yes

□ No

□ Can't answer

□ Not applicable

8. Was the scientific quality of the included studies used appropriately in formulating conclusions?

The results of the methodological rigor and scientific quality should be considered in the analysis and the conclusions of

the review, and explicitly stated in formulating recommendations.

Note: Might say something such as “the results should be interpreted with caution due to poor quality of included

studies.” Cannot score “yes” for this question if scored “no” for question 7.

□ Yes

□ No

□ Can't answer

□ Not applicable

9. Were the methods used to combine the findings of studies appropriate?

For the pooled results, a test should be done to ensure the studies were combinable, to assess their homogeneity (i.e.,

Chi-squared test for homogeneity, I2). If heterogeneity exists a random effects model should be used and/or the clinical

appropriateness of combining should be taken into consideration (i.e., is it sensible to combine?).

Note: Indicate “yes” if they mention or describe heterogeneity, i.e., if they explain that they cannot pool because of

heterogeneity/variability between interventions.

□ Yes

□ No

□ Can't answer

□ Not applicable

10. Was the likelihood of publication bias assessed?

An assessment of publication bias should include a combination of graphical aids (e.g., funnel plot, other available

tests) and/or statistical tests (e.g., Egger regression test, Hedges-Olken).

Note: If no test values or funnel plot included, score “no”. Score “yes” if mentions that publication bias could not be

assessed because there were fewer than 10 included studies.

□ Yes

□ No

□ Can't answer

□ Not applicable

11. Was the conflict of interest included?

Potential sources of support should be clearly acknowledged in both the systematic review and the included studies.

Note: To get a “yes,” must indicate source of funding or support for the systematic review AND for each of the included

studies.

□ Yes

□ No

□ Can't answer

□ Not applicable

Shea et al. BMC Medical Research Methodology 2007 7:10 doi:10.1186/1471-2288-7-10

Additional notes (in italics) made by Michelle Weir, Julia Worswick, and Carolyn Wayne based on conversations with

Bev Shea and/or Jeremy Grimshaw in June and October 2008 and July and September 2010.

82

The IHE checklist for case series

Case Series: 18-criteria checklist

Study objective

1.Is the hypothesis/ aim/ objective of the study

stated clearly in the abstract, introduction, or

methods section?

Study population

2.Are the characteristics of the participants

included in the study described?

3.Were the cases collected in more than one

centre?

4.Are the eligibility criteria (inclusion and

exclusion criteria) for entry into the study

explicit and appropriate?

5.Were participants recruited consecutively?

6.Did participants enter the study at a similar

point in the disease?

Intervention and co-intervention

7.Was the intervention clearly described in the

study?

8.Were additional interventions (co-

interventions) clearly reported in the study?

Outcome measure

9.Are the outcome measures clearly defined in

the introduction or methods section?

10.Were relevant outcomes appropriately

measured with objective and/or subjective

methods?

11.Were outcomes measured before and after

intervention?

Statistical analysis

12.Were the statistical tests used to assess the

relevant outcomes appropriate?

Results and conclusions

13.Was the lenght of follow-up reported?

14.Was the loss to follow-up reported?

15.Does the study design provide estimates of

the random variability in the data analysis of

relevant outcomes?

16.Are adverse events reported?

17.Are the conclusions of the study supported by

results?

Competing interests and sources of support

18.Are both competing interests and sources of

support for the study reported?

83

Checklist for potential ethical, organisational, social and legal aspects

1. Ethical

1.1. Does the introduction of VABB and its potential use/ non-use instead of the

defined, existing comparator(s) give rise to any new ethical issues (equal access

to the treatment, resource allocation/shortage etc.)?

No

1.2. Does comparing VABB to the defined, existing comparators point to any

differences which may be ethically relevant? No

2. Organisational


defined, existing comparators require organisational changes in terms of training

in procedure, need for facilities, equipment and resources?

Yes


differences which may be organisationally relevant (e.g. shift from primary to

secondary care, transportation, etc.)?

No

3. Social


defined, existing comparator(s) give rise to any new social issues? No


differences which may be socially relevant? No

4. Legal


defined, existing comparator(s) give rise to any legal issues? Yes


differences which may be legally relevant? Yes

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