File: Breast Cancer Protocol 24-6-04(R 18-10-04).doc

Taskforce on Clinical Pathway Model on Management of Breast Cancer Membership Convener: Prof. Angus CW Chan / Dr. H T Leong

Members: Dr. Gordon Au

Dr. Miranda Chan

Dr. Polly Cheung

Dr. Louis Chow

Dr. P S Kan

Dr. W H Kwan

Dr. Tina Lam

Dr. Bonita Law

Dr. Amy Pang

Dr. S K Tang

**Protocol drafted by Dr LAW Ka Bo, Bonita Angela,

Specialist surgeon

Director, Union Breast Centre,

Union Hospital, Shatin

June 2004

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Clinical Pathway Model on Management of Breast Cancer

Contents

A. Introduction B. Referral Protocol for Primary Care Physician C. Management protocol for referred suspicious breast cancer cases:-

The Breast Team 1) Workflow: clinical, radiological, pathological 2) Surgery: choice of surgery, sentinel node biopsy, reconstruction 3) Adjuvant therapy: chemotherapy, radiotherapy, hormonal

manipulation (see separate oncology protocol) 4) Surveillance plan: where to follow up, frequency of FU & FU

scans, note for recurrence/complications of treatments

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A. Introduction 1. Carcinoma of breast is the most common cancer amongst females in

Hong Kong. According to the latest HK Cancer Registry (1999), the age standardized rate was 58/100 000 with annual new cases amounting to more than 1900 per year. Such rates were observed to be in a rising trend. Our modal age of onset lied within the 40-55 age group, which bears a significant socio-economical burden.

2. The present report aims to introduce a framework for the management of

breast cancer. While we realize and accept there are different approaches to the same problem, it is hoped that many of the guidelines mentioned herein help to clear some controversies and ensure a minimum standard of care delivered to our patients. Emphasis is put on evidence-based medicine and multidisciplinary participation, rather than strict adherence to the guidelines.

B. Referral Protocol for Primary Care Physician Indications of Referral to Specialist Breast Clinic : 3. In summary, the following conditions (with regards to breast cancer)

should be preferably referred to specialist breast clinic:- a. Management of diagnosed breast cancers* b. Suspicious symptoms of breast cancer which requires further

investigations c. Presence of breast symptoms on a background of strong family

history of breast cancer (if two or more relatives and/or cancer occurs in a relative before the age of 50)

d. Relevant breast symptoms in a patient aged 40 or above e. Benign breast diseases for management

* Diagnosed breast cancer patients (as described on referrals) will be

offered an appointment within 2 weeks to facilitate further management.

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C. Management protocol for referred suspicious breast cancer cases

The Interdisciplinary Breast Team 4. An inter-disciplinary Breast Team Approach should be adopted to

manage breast cancer patients. 5. Specialist breast surgeons contribute in coordinating the overall

management among all disciplines. Dedicated radiologists, pathologists, oncologists & radiotherapists are active key members of the Team. Plastic surgeons with special interest are available to advice & thus offer breast reconstruction.

6. Nurse specialists serve in counseling & facilitating pre-operative

management as well as supporting patients during the adjuvant therapy periods & thereafter.

7. Paramedical support is another prerequisite for running a successful

breast service. Physiotherapists & occupational therapists with experience & trainings in post-operative care on our patients are participating actively. Psychologists will be involved in cases with strong emotional turmoil.

Radiology 8. Imaging tests are to be offered to all symptomatic clients for evaluation &

relevant cytological/histological tests thus performed (“Triple Test”). 9. For patients younger than 35, only whole breast USG is performed &

MMG performed only if indicated. This reduces radiation exposure in younger clients. Secondly, the dense breasts in young Chinese increases the false negative rate for carcinoma detection by MMG.

10. For patients older than 35, complementary USG & MMG will be

performed to supplement each other.

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11. MMG is performed in 2 views, medial lateral oblique (MLO) & cranio-caudal (CC). Additional views such as cone magnification views will be supplemented if abnormality is encountered.

Standard report of breast imaging 12. Reporting is generally adhered to the Breast Imaging Reporting & Data

System ( BI-RADS ) lexicon recommended by the American College of Radiologist. Some local modifications with addition of sonographic findings ( as recommended by ACR 2001 ) are adopted. This served as a general guideline to be followed and is by no means final.

a. Clinical history: should be offered in the request form with clear

indication of tests requested ( eg FNA vs Core biopsy ) b. Mammographic report:

- breast composition - abnormalities:

i. Density ii. Mass: shape/margin/distortion iii. Calcifications: macro or micro, cluster/group, linear,

segmental, diffuse/scattered ( benign/intermediate/suspicious )

iv. Size v. Associated findings: architectural distortion, nipple-areolar

complex, skin, axilla iv. Location

c. Sonographic findings

- abnormalities i. Mass: shape/margin/orientation(w/d ratio)/posterior acoustic shadowing/enhancement, echopattern, heterogeneous or

homogeneous, hyper, hypo, or anechoeic Cyst: simple/complex ii. Size iii. Location iv. Skin, axillae

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d. Overall impression

- BIRAD 0 incomplete assessment, further investigation required 1 normal 2 benign 3 probably benign: follow up in 6-12 months 4a mildly suspicious (indeterminate): biopsy indicated 4b suspicious: biopsy indicated 5 typical picture of malignancy: biopsy to establish diagnosis

13. Attached herewith a self-explanatory flow chart (Appendix I) on the

radiological investigation of symptomatic breast patients.

Pathology 14. Cytopathology or histopathology (FNA, core biopsy, or excisional biopsy)

is recommended for definitive diagnosis of breast cancers, and to investigate the nature of indeterminate or suspicious lesions.

Other pre-operative workups 15. The selection of other investigation modalities should be individually

determined. 16. Full blood count & serum biochemistry ( RFT, LFT, Bone Profile ) give

important information of the general well being of the patient & serve as screening tool for further investigations.

17. Chest radiography is recommended for pre-operative assessment as well

as metastatic screening. 18. Bone scan, computed tomography & PET scanning have a low diagnostic

yield in asymptomatic patients . Thus these tests are only indicated in the following situations:-

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a. Deranged LFT b. Palpable abdominal mass, eg hepatomegaly c. Bone pain d. Bony tenderness e. Locally advanced disease ( T3 or T4 ) or palpable lymphadenopathy

19. Serological tests for cancer-specific antigens ( eg CEA, CA 153 ) have been used to monitor status of breast cancer after cancer treatment but have low sensitivity and therefore should be reserved for use in trials or advanced breast cancer with high risk for recurrence.

Key points in diagnosis of Breast Cancers 20. Preoperative imaging is mandatory to assess the extent of local disease

& to determine the choice of local treatment. 21. Preoperative histological proof should be established in >90% cases. 22. Routine high power metastatic workup is not indicated unless

clinical/biochemical suspicions arise or in locally advanced cases. Formulation of treatment plan 23. Once the diagnosis of cancer is established, patient together with her

relatives ( if she prefers ) should be interviewed by the specialist surgeon, medical oncologist & radiation oncologist, with the help of a breast care nurse.

24. Diagnosis will be reviewed with treatment options explained with or

without the assistance of audio-visual aids. 25. Treatment plan will thus be formulated.

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Surgery & Radiotherapy: Invasive Carcinoma Appendix II The Breast 26. Majority of newly presented cancer cases are early breast cancers for

which surgery is essential in achieving cure. 27. The aim of surgery for primary breast cancer is to eradicate the primary

tumour & any local extension in the hope of achieving total disease control.

28. Surgical options range from breast conservation (BCT), partial or total

mastectomy with or without reconstruction. Breast conservation therapy (BCT) 29. BCT confers total excision of the tumour with adequate margin (generally

recommended margin >1cm), together with axillary treatment. 30. Quadrantectomy is widely advocated by the Italian authorities whereas

the more generally accepted option is wide local excision with clear margins on histology.

31. Post operative whole breast irradiation is at present the standard of care

after breast conserving surgery as local recurrence rate is shown to be doubled as compared with mastectomy if such is not carried out. The irradiation ( total dose of 55Gy ) will be delivered within 6 weeks duration ( 25-30 sessions ).

32. Patient suitable for BCT:

a. Small tumour size in relation to breast size b. Mammogram does not show multicentric disease in the same breast c. No contraindication for irradiation (i.e. pregnancy, dermatomyositis or

other autoimmune disease as felt contraindicated after immunologist assessment, previous history of irradiation to breast, cardiac disease with left breast tumours)

d. Patient is keen to conserve her breast e. Patient is fit enough to go to oncology unit for repeated outpatient

treatment

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33. Surgical markers (eg surgical clips) should be used to mark the exact

tumour bed so as to facilitate RT planning. 34. The choice of BCT over mastectomy depends on tumour factors (size,

location, multi-focality) & patient factors (breast size, patient’s preference, previous irradiation & contra-indication to irradiation). The final decision should be based on both physician recommendation and patient’s preference.

35. Pre-operative imaging, namely mammogram, is mandatory in order to

detect synchronous, multi-focal or multicentric disease in which case BCT will be contra-indicated.

36. The overall survival & local recurrence rate are comparable between BCT

& mastectomy. The overall staging ( ie whether nodal metastasis is present ) and presence of palpable axillary nodes bears no contra-indication to BCT.

37. BCT may be considered & offered in all breast cancer cases unless

contraindicated.

Mastectomy 38. Modified radical mastectomy (MRM) has become the gold standard for

breast cancer treatment since 1970’s when result in trials demonstrated that the survival thus conferred is comparable to that after Halsted’s radical mastectomy.

39. The MRM we now employ consists of total mastectomy & level II axillary

dissection. 40. Post mastectomy chest wall irradiation will be considered if the deep

margins are close or for large T2 or T3 tumours.

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Mastectomy with reconstruction

Patient led demand 41. Mastectomy is proposed in cases which BCT is not feasible or when

patient prefers. Options of reconstruction should be offered & patient should be encouraged for such options.

42. Common reconstructive options are:

a. Breast Saline or silicone prosthesis b. Transverse rectus abdominous myocutaneous flap ( TRAM flap ) c. Latissimus dorsi flap +/- breast prosthesis (LD flap) d. Deep inferior epigastric perforator flap (DIEP flap) e. Composite flap with breast prosthesis

43. Skin sparing total mastectomy confers better cosmetic result in cases of

autologous tissue reconstruction. The oncological safety of skin sparing mastectomy has not yet been documented in advanced tumours ( T3 or above ).

44. The indication should be carefully tailored.

Immediate vs delayed reconstruction 45. We advocate immediate reconstruction whenever possible due to the

superior cosmetic as well as psychological outcomes.

The axilla Axillary dissection 46. The standard axillary treatment for invasive cancers is Level II dissection

as a fair balance between surgical trauma & clearance ( vs Level III ). 47. Cherry –picking type of axillary sampling should not be recommended.

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Sentinel node biopsy 48. Advantages:-

a. Eliminate unnecessary axillary dissection b. Facilitate targeted detailed pathological examination of axillary nodes

( prognostic significance ) 49. A standardized procedure involving a team of nuclear medicine physician

or radiologist, surgeon & pathologist is preferable for highest yield and accuracy. The set up should be specific for each individual centre. Only centres with trained personnel in the above aspects & with a learning period of more than 20 cases (with validation from full level II axillary dissection with identification rate >92% & accuracy >96% ) can perform therapeutic sentinel node biopsy. Frozen section on sentinel node is not mandatory and it is reasonable to perform full axillary dissection at a second stage if the sentinel node is positive on paraffin histology.

50. Long term result of sentinel node biopsy with regards to axillary

recurrence & survival is not available. 51. Recommended indication: solitary tumour <3cm in size with no clinical or

radiological evidence of axillary metastasis. Previous irradiation & systemic neoadjuvant chemotherapy are not indicated for sentinel node biopsy except for trials.

52. All sentinel nodes will be sectioned in step cut manner & thus submitted

to both H&E & immunohistochemical staining.

Suggested Guidelines for Histological Reporting

53. The following should be included in the report:- a. Type of surgery, as indicated on the request form by the surgeon b. Site of disease ( L / R, quadrant ) c. Macroscopic & microscopic size d. Histological type e. Grading ( applies to DCIS also ) f. Presence of extensive DCIS and its grade

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g. Presence or absence of Lymphovascular invasion h. Lymph node status - total number, number involved, whether

capsular infiltration or matted i. Resection margin status (resection margin - minimal distance from

tumour to margin in mm) j. Oestrogen / Progestogen Receptor Status (staining intensity & tumor

cell positivity in %) k. C-erb-B2 over-expression / amplification l. Final diagnosis - with Histology , Lymph Node Status, Receptor

Status and other factors which affects treatment, eg proliferation index.

54. For reporting details, please refer to the proposed guidelines from COC(Pathology).

Surgery & Radiotherapy: in situ carcinoma (DCIS) Appendix III 55. By definition, in situ disease confines itself to the breast & theoretically

does not metastasize. Local treatment should thus confer cure to in situ disease & axillary surgery & systemic chemotherapy is not indicated.

56. Chemotherapy is not indicated in in situ carcinoma. 57. The modified Van Nuy’s Prognostic Scoring system ( namely the tumour

size, grading +/- necrosis and surgical margins, and age ) could be used to determine the options of wide local excision +/- radiotherapy & mastectomy.

Adjuvant chemotherapy therapy ( refer to HA oncology guidelines) The surveillance plan after cancer treatment 58. The goals of follow up include:-

a. Detection of local or distant recurrence b. Detection of treatment toxicities c. Provision of psychosocial support

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59. As about 10% of cancer survivors will ultimately in their lives experience a

second breast cancer, long term surveillance programme is mandatory. 60. Currently, newly treated cancer patients will be followed up in 3-4 months

intervals in the first 1-2 years after treatment and every 6 monthly thereafter till 5 years & thus yearly till 10 years.

61. Mammographic surveillance is offered every year. 62. For BCT cases, the first surveillance imaging will be scheduled after RT is

completed as a baseline. 63. Routine USG liver, bone scan, CXR are not indicated unless related

symptoms arise. 64. Routine blood checking for tumour markers (CA 153) carries low

sensitivity and therefore not recommended. 65. Patient on tamoxifen will be recommended for routine yearly

gynaecological check up which should include USG scan of the uterus to detect early endometrial changes.

-- End --

USG +/- MMG

Normal

Biopsy (FNAC/Core Biopsy)

Benign Atypia Malignant

Repeat Biopsy or

Other form of

excisional Biopsy

Benign Probably benign; Indeterminate/Mildly suspicious

Follow- up

Malignant (Histology preferred for

definitive diagnosis)

Appendix I

Flowchart on Radiological Investigation of Symptomatic Breast Patients

Remarks: Arrangement for biopsy depends on the extent of cytology support For probably benign lesion, ACR Recommendation of short term follow up may be followed

Plan for definitive treatment

Follow Up

( refer to text for sentinel node biopsy ) (Option of Neoadjuvant chemotherapy)

T1, T2

Breast Conservation Surgery (ie WLE + Axillary dissection)

Modify Radical Mastectomy

Ca Breast – Treatment Flow Chart 2 (Surgery & Adjuvant Radiotherapy)

Node -ve

Node +ve

RT to intact breast

RT to breast +/- regional nodes

T3, T4 Option of neo-adjuvant therapy

Node -ve

Node +ve

RT to chest wall (Marking of apex for grossly involved node for RT planning

RT to chest wall & regional nodes

Chest wall irradiation if margin close or large T2 or lymph-vascular infiltration

Breast Conservation Surgery (ie WLE + Axillary dissection)

Modify Radical Mastectomy

Appendix II

Ductal Carcinoma in Situ (DCIS)*

Multicentric & Multifocal DCIS

Complete Local Excision

Breast Irradiation

Localized DCIS

Mastectomy

Incomplete (+ve margin)

Ca Breast – Treatment Flow Chart 1

Wide Local Excision

Mastectomy (Axillary dissection is not indicated in general)

Referral to a specialized oncology center

Referral to a specialized oncology center

Appendix III