« Israeli-French Breast Cancer Update »Prevention, Detection and Treatment,

Multidisciplinary approach

Dr Jean-Yves SEROR (Paris, France)

Small lesions ≤ 1 cm.

Imaging features.

T1a > 1mm and < 5mm T1b > 5 mm and < 10mmT1c > 10mm et < 20 mm

Global survival at 5 years vs size

S < 20 mm 91 %

20 < S < 50 mm 80 %

S > 50 mm 60 %

Definition TNM T1a and T1b (T1< 20 mm)

Cancello & al, Br Can res and TTT 2011

N+

N-

T < 10 mm

Recurrence at 10 years <10%

• Tumors most frequently not palpable, detected through screening• Infra-centimetric = Not palpable

• HER2 + • Triple Negative• Young old patientGood prognosis

BiologicalHeterogenicity

In France , the infra centimetric breast cancers represent today 25 to 30 % of these newly diagnosed cancers.

37 % of the invasive cancers diagnosed within this screening campaign have a size ≤ 10mm

France : National Breast Cancer Screening

Tumor size : The largest diameter of the bigger tumoral

nodule present

Definitions

In case of difference between the macroscopic and microscopic measure, the

microscopic measure of the invasive contingent should be taken into account

for the grading

Lobular Invasive carcinoma: underestimation of the size

7 mm

• When measuring, do not take into account

the in situ adjacent carcinomas

• In case of multiple tumor, do not sum sizes

Uni focalinfra-centimetric

tumor

infra-centimetric tumor + DCIS (microcalcifications)

TOMOSYNTESIS

Not taking into account in the measurement , the

DCIS adjacent

Infra-centrimetric tumor : UNIFOCAL

In case of multiple tumor

• Do not sum the sizes for the TNM

• Total size : surgical management

Infra centimetric tumors : MULTIFOCAL

Tumoral distribution

Regarding small size tumors (≤ 9 mm), vascular embolus and nodes extension are most frequent for multifocal tumors 1

71. Tot T, Pekár G, Hofmeyer S, et al. The distribution of lesions in 1-14-mm invasive breast carcinomas and its relation to metastatic potential. Virchows Arch. 2009 Aug;455(2):109-15.

137 tumors between 1 & 9 mm (55 %)Unifocal tumors Multifocal tumors

Invasive carcinoma 1-9 mm 97 71 % 40 29 %

Vascular embolus 9 9 % 14 35 %RR = 3.814495 % CI = 1.7960-8.0870

Ganglionic extension 5 5 % 5 13 %RR = 2.425095 % CI = 1.7424-7.9266

Infra centimetric tumors and mammography

Infra centimetric tumors and ultrasound

Infra centimetric tumors and MRI

Imaging specificities for lesions < 1 cm

9

Infra centimetric tumors and mammography

Compared to tumors > 2 cm, detection of infra centrimetric tumors not

seen on mammography but only under ultrasound 1: x 2,21. Bae MS, Han W, Koo HR et al. Characteristics of breast cancers detected by ultrasound screening in women with negative mammograms.

Cancer Sci. 2011 Oct;102(10):1862-7.

Se 80% [78-82%]Density 1 98%Density 2 83%Density 3 64%Density 4 48%

2. DEMIST Digital Mammographic ImagingScreeningTrial ) Pisano ED et al. New Engl. J. Med 2005

The mammography sensitivity is related to the breast density

• The higher the breast density, the lower the detection sensitivity1

• Variation of 64 % for breasts with a very high density to 87 % for very fatty breasts 2

7 mm

Infra centimetric tumors and mammography

16 %

43 %

21 %

43 %

Isolated microcalcifications cluster ( 43% ) Indicating an in situ lesion

Rounded ( 20 %) or spiculated opacity (21%)

Opacity and microcalcifications ( 16 % )

Inv Carcinoma

Radial scar

With mammography small cancers can be seen : microcalcifications

Bi-Rads 3 BIRADS 4 ?

• Analysis and detection of microcalcifications clusters on X-ray images Magnification views +++

• BIRADS : THE MORPHOLOGY is the first semiologic element to be taken into account before the evolvement

Diagnostic pitfall

13 months

DCIS comédo

1. Berg WA et al Cystic breast masses and the acrin 6666 experience. Radiol Clin North Am 2010;48:931-87

• These small rounded tumors should not be wrongly interpreted as intra-mammary lymph nodes.

• You should be careful with stable lesions compared with the last medical balance and with lesions not found again under ultrasound.

• Women with Family history ++ Misleading aspect of some lesions : rounded, regular, pseudo cystic image.

With mammography small cancers can be seen (follow) : Round tumor with benign appearance 1

Diagnostic pitfall

P David, J Le Sein Septembre 2004)

Relation between size and tumoral growth

Misleading rounded shapesIrregular outlines

Bi-Rads 3 : if follow up ….

Opacity control at 4 months Microcalcifications at 6 months

• Growth speed• Intensity of the surrounding tissue reaction

2009

2009

Bi-Rads 2 ? Bi-Rads 3 ?

Eric L Rosen and al Malignant Lesions Initially Subjected to Short-term Mammographic Follow-up Radiology 2002;223:221-228

2011 2011

Rosen: 4/12 opacities classified as node

3. Burrell HC, Sibbering DM, Wilson AR et al. Screening interval breastcancer : mammographic features and pronostic factors. Radiology1996;199:811-7. 4. Andersson I, Ikeda DM, Zackrisson S et al. Breast tomosynthesis and digital mammography: a comparison of breast cancer visibility and BIRADS classification in a population of cancers with subtle mammographic findings. Eur Radiol. 2008 Dec;18(12):2817-25.

15

• Variation of the aspect according to the incidence or visibility under a sole incidence

• The most frequent cause of interval cancers 3

• The breast tomosynthesis by reducing the tumor and gland superposition effects , should improve the sensibility versus the mammography 4

With mammography small cancers can be seen as : architectural distortion

Diagnostic pitfall

2010 2012

Invasive carcinome

4 radiologists

12631 womenCancer n = 121

Mammo 2D Mammo 2D+

Mammo 3D2 incidences

Delta p

False positives 6,1% 5,3% 15% P < 0,001

Cancers detection

121 soit 9,5 %o

77/121

6,1%o

101/121

8%o

24

27%P < 0,001

Invasive cancers detection

56

4,4%o

81

6,4%o

25

40%P < 0,001

Oslo trial Nov 2010 – Dec 2011 25 000 women

Comparison of digital mammography alone and digital mammography plus tomosynthesis in a population-based screening program.

Skaane P et Al. Radiology. 2013 Apr;267(1):47-56.

BIRADS 0 ?

Doubt in mammography with an abnormality not accessible for a biopsy under ultrasound or stereotaxy

Doubtin mammography

ACR 4

Negative Predictive Value :Normal MRI allows to clear these images

In front of a small tumor detected under ultrasound, the signs with the highest cancer positive predictive value are :

The irregular shape : 62 %

The orientation not parallel to the skin : 69 %

The spiculated margins : 86 %

1 sign only : eliminate the benignancy

Ultrasound signs : T1b > T1a

Infra centimetric tumors and ultrasound

The diagnostic value of the ultrasound is superior if the echography is guided by an abnormality detected on the mammography vs screening ultrasound

1. Iso-echogenic lesions (10 % of cancers)

2. Some high grade small cancers

Posterior reinforcement of the ultrasonic beam due to their high cellularity

Regular margins due to their fast growth

Histology : Papillary carcinoma

Infra-centimetric tumors and ultrasound

Diagnostic Pitfall

1 2 3

Cysts , fibroadenoma and carcinoma ?

Medularry CarcinomaSize 10 mm RH- Her2 +

Post puncture

Masses Enhancement(visible tumor in 3 planes > 5mm)

Non mass Enhancement Foci each enchancement < 5mm

Enhancing lesions

Sensibility 1,2 95-100 % in infiltrative Carcinoma

70-75 % in Ductal carcinoma In situ (DCIS)

1 Liberman L, Morris EA, Joo-Young Lee M et al. AJR Breast lesions detected on MR Imaging: features and positive predictive value. AJR 2002;179:171-178 2 Schelfout K, Van Goethem M, Kersschot E, et al. Preoperative breast MRI in patients with invasive lobular breast cancer. Eur. Radiol 2004;14:1209–1216. 3 Fabre Demard N, Boulet P, Prat X et al. Breast MRI in invasive lobular carcinoma: diagnosis and staging].J Radiol 2005;86(Pt 1):1027–1034.

Infra centimetric tumors and RMI

73% Invasive carcinoma

• DCIS• Invasive lobular carcinoma 3

Focal adenosis,Invasive carcinoma, DCIS, papilloma, fibroadenoma, LN…

False negatives: the causes

Weak tumoral angiogenesis and therefore low enhancement :

• Histological type (5 % of the RMI FN)

Ductal Carcinoma In situ (DCIS)

Medularry Carcinoma Breast

Some Invasive Lobular Carcinoma (ILC) or with a consequent fibrous contingent

• Small size cancers (Up to 3 % of false negative)

Infra centimetric tumors and RMI

Diagnostic Pitfall

Enhancement

Absent (few or no angiogenesis)

Not seen (masked effect)

Wrong interpretation (Focus)

Be careful with the mammary gland PHYSIOLOGICAL ENHANCEMENT particularly during the 2nd part of the menstruation ( RMI exam to be performed between the 7th and 13rd day of the menstruation)

Background Parenchymal Enhancement : risk of hiding a small lesion

minimal mild

moderate marked

Bi-Rads IRM 2013

28

• FOCI 1,2 CARACTERIZATION

Punctiform enhancements < 5 mm

Not visible before injection +++ (T1 / T2)

Unique or multiple

• Up to 29 % of the patients presenting a suspicious lesion under mammography or ultrasound

1. Kuhl CK, Kreft BP, Hauswirth A et al. [MR mammography at 0.5 tesla. II. The capacity to differentiate malignant and benign lesions in MR mammography at 0.5 and 1.5 T].] Rofo 1995 Jun;162(6):482-91.

2. Brown J, Smith RC, Lee CH. Incidental enhancing lesions found on MR imaging of the breast. AJR Am J Roentgenol. 2001 May;176(5):1249-54.

Infra centimetric breast carcinoma and RMI

Mass enhancement :

Invasive ductal CarcinomaFoci : Non mass enhancement < 5mm

CCI SBR2 Re+ Rp- Her2 -

Right Breast ultrasound

45% echo-guided biopsy55 % of the lesions not found

DeMartini et al. Utility of Targeted Sonography for Breast Lesions That Were Suspicious on MRI. AJR 2009;192:1128

SECOND LOOK ULTRASOUND

VPP 96 % T > 20 MMVPP 62% T < 20 MM

Microcalcifications

NME > 5 mm

Infra centimetric lesions : biopsies

Pre-operatory diagnosis

Difficult Extemporaneous

Malignity Infiltrating ? Prognosis factors

Grade HER2 +++ Hormonal

status

Lesions spreading

Limits and difficulties of infra-centimetric lesions echo-guided microbiopsies ( T1a < 5 mm)

Small size lesions?

3 -4 mm ? Visibility

Post biopsy for small size lesions

Pre-operatory localizationX-ray ultrasound correlationX-ray of the operative element

After biopsy of small lesions(< 5mm)

“The mean size of such image-detected carcinomas is 11mm and 90% will be node negative.”

“Errors in determining tumor size result from

summing the sizes of the carcinoma

• In multiple separate morcellated fragments of a resection

• Or in the multiple separate fragments of a core biopsy procedure.”

Issues with Tumor Size Assessment Michael Lagios, MD Seminars Breast Disease 2006, Volume 3, No. 9

T1a et T1b

20 mm

10

mm

Conclusion Small lesions ≤ 1 cm. Imaging Features.

• Tumors with a good prognosis but up to 20% are N+• Clinical exam + imaging : early diagnosis

• Delayed diagnosis : Pitfall Histological Screening Misleading appearance

• Importance of a high quality imaging, knowing the limits.

• Pre-operative diagnosis +++

• In case of doubt, sampling rather than close control

Dr Jean-Yves SEROR (Paris, France)

« Israeli-French Breast Cancer Update »Prevention, Detection and Treatment,

Multidisciplinary approach

Small lesions ≤ 1 cm.

Imaging features.