Breast Cancer

1. Breast Cancer Who Gets What Type of Surgery? Murray Pfeifer 16th August, 2014

2. History of Breast Cancer Treatment • Hipppocrates (460-375BC) spoke of two cases • Galen (129-200AD) • Humoral theory • Linked to melancholia • Likened to a ‘crab’ • Recognised the merit of local excision were possible • LeDran 1757 proposed the theory that breast cancer is a local disease • Spread at first occurs through the lymphatics to lymph nodes before subsequently entering the general circulation • This hypothesis suggests that breast cancer can be cured if treated early with aggressive surgery to the breast. • This ‘local theory’ prevailed for about two centuries and was the basis on which radical breast operations were offered to women

3. The Modern Era (1) W Sampson Handley’s ‘Theory of Lymphatic Permeation’ was mooted around 1860 Centrifugal lymphatic permeation is the mechanism for the spread of cancer This gave support to the radical operations being advocated by Halstead, Moore and others McWhirter – simple mastectomy supplemented with XRT resulted in the same survival as patients who had radical surgery

4. The Modern Era (2) Bernard Fisher: Lymph nodes not an effective barrier to spread Cancer cells pass easily back and forth between lymphatics and blood vessels Spread of cancer therefore not an orderly progression from lymphatics to blood stream Gershon-Cohen: Breast cancers have a protracted period of occult growth during which time they have a ample opportunity to metastasize This limits the surgical curability of breast cancer These theories of breast cancer spread were widely adopted and started a movement to less aggressive surgery

5. Who gets surgery? • Almost all women with invasive and in situ breast cancer will receive surgery as part of their management • Purpose of surgery: • To control the locoregional disease by • Extirpation of the primary tumour • Removal of involved regional lymph nodes • Relative contraindications to surgery: • Advanced age and frailty • Advanced disease

6. What are the operations that are available to us to manage invasive breast cancer? • For the primary lesion in the breast: • Mastectomy • Wide local excision • +/- breast reconstruction • Immediate • delayed • For the axilla: • Sentinel node biopsy • Axillary clearance

7. Mastectomy: Mastectomy has become increasingly conservative as a result of our better understanding of tumour biology Simple mastectomy aims to remove almost all breast tissue including the axillary tail of the breast, the nipple/ areolar complex, and the underlying pectoral fascia The need for XRT is obviated in most cases

8. Indications for simple mastectomy: • Large tumour/ small breast • Centrally located tumour • Multifocal and multicentric cancers • Recurrence of cancer previously managed by breast conserving treatment • Patient choice • Arguably lower local recurrence rates • Avoidance of XRT • Social aspects of access to XRT at a remote site

9. Breast Conserving Treatment: Wide local excision And Radiotherapy Radiotherapy after BCT is mandatory • NSABP B-06 • recurrence rate after surgery alone – 35% • Recurrence rate after surgery and XRT – 10%

10. Objectives of Breast Conserving Treatment(BCT): Good control of the primary cancer Survival equivalence to mastectomy Cosmetically acceptable outcome

11. Good control of the primary tumour: Ipsilateral Breast Tumour Recurrence(IBTR) represents local therapeutic failure and psychological stress for the patient Minimising IBTR depends on adequate resection of the primary tumour and good radiotherapy to the breast Risk of dissemination of tumour is increased and survival decreased after local recurrence IBTR increases risk of dissemination by 3-4x (Fisher et)

12. How much is enough? Criteria for acceptable margins is, with time becoming more conservative • Previous standard: • Ideal >1cm • Close but acceptable 5mm-1mm • ASTRO and SSO consensus guideline Feb 2014 • Meta-analysis 33 studies; 28,162 patients • Positive margins are associated with a >2x risk of IBTR • Negative margins (no ink on tumour)optimise IBTR. Wider margins do not lower risk • Rates of IBTR are reduced with use of systemic therapy

13. Contraindications to BCT More than one tumour Large tumour, small breast Diffuse, suspicious microcalcifications Previous radiotherapy to the breast Collagen disorders may result in an adverse response to XRT Central tumours where there is a need to excise the nipple/areolar complex Patient choice with respect to XRT

14. Morbidity of BCT: Poor cosmesis Wound complications Altered nipple sensation Initial inflammation in the skin post XRT Later skin thickening and woody contracture of the breast Post XRT fatigue Radiation damage to underlying lung and heart Radiation induced neoplasms egangiosarcoma (1 in 476 patients) Risk of salvage mastectomy

15. Is there a survival equivalence between BCT and Mastectomy in STI-II cancers: Yes there is!! Numerous controlled trials have consistently demonstrated this point Early Breast Trialist Group meta-analysis of 7 RCTs showed no difference in 10 year overall survival rates

16. Surgery of the axilla: Decisions about management of the axilla are made quite independently from decisions about the management of the primary cancer

17. Why operate on the axilla? To assess prognosis To ‘stage’ the disease for purposes of determining indication for adjuvant systemic therapies and radiotherapy To resect disease that might be present in the axillary lymph nodes.

18. Who gets axillary surgery? • Almost all women with invasive breast cancer • Selected women with DCIS • Published data – Upgrade diagnosis of DCIS on core bx in around 20% (range 13-40%) • About 10% of patients with high risk DCIS have +ve sentinel node (high risk=high grade, large size) • Indications for sentinel node biopsy: • High grade • Large lesion • Extensive involvement • mastectomy

19. The Operations Two Operations: • Sentinel node biopsy • Axillary dissection

20. Sentinel lymph node biopsy The sentinel lymph node is the hypothetical first node or group of nodes draining a cancer First mooted by Gould (1960) for parotid cancer Popularised by Cabanas for penile cancer Used extensively in breast cancer, melanoma, and head and neck cancer

21. Who gets Sentinel node biopsy? • Women who have invasive breast cancer and fulfil the following criteria: • Small tumour (T1 or T2) • No identifiable axillary lymph node involvement • Exclusions: • Large tumours (T3 or T4) • Suspicious or proven positive axillary nodes • Prior axillary surgery • Prior cosmetic breast surgery • Following neoadjuvant systemic therapy

22. Sentinel node biopsy – principles Combined technique of vital blue dye and radioisotope. Technitiumlabelledsulphur colloid injected the day prior to surgery. Usually accompanied by scintngram and CT SPECT Blue dye > periareolar injection after induction of anaesthesia Combined technique associated with a higher degree of identification of the sentinel node than the use of one or other technique alone.

23. Sentinel node biopsy principles Node(s) can either be sent for frozen section whilst the patient is on the table with a view to completing the axillary dissection if positive Or Node(s) can be sent for paraffin section with a view to subsequent further treatment if positive

24. How reliable is sentinel node biopsy? • Numerous studies including NSABP B-32, ALMANAC, Milan, and SNAC1 have reported: • A success rate of 90-98% • False negative rate 5.5 – 15.7% • Our own SNAC trial reported a false negative rate - 5.5%

25. Management of the axilla where there has been a positive sentinel node biopsy • Controversial but usually completion axillary dissection +/- radiotherapy • Management is tending to become more conservative • Isolated tumour cells and micrometastases are usually managed with radiotherapy only • More extensive axillary disease is now being managed by XRT alone

26. EORCT AMAROS StudyASCO 2013 – Emeil Rutgers • RCT – Surgery v XRT • Five year follow up • Results: • Local recurrence 0.54% v 1.03% • Disease free survival 86.7% v 82.7% • Overall survival 93.3% v 92.5% • Lymphoedema 28% v 14%

27. Axillary Dissection Does it still have place? Yes……. But less so than in years gone by

28. Axillary dissection – why we do it • Stage the axilla for prognosis • Inform the planning of adjuvant therapies • Locoregional control of disease • 30-40% of patients presenting with breast cancer have disease in the axillary nodes • Recurrence rate after axillary dissection <2% • Therefore an improvement in DFS • Possible improvement in overall survival (but note NSABP B-04 – no survival advantage for patients with clinically negative axilla who had ALND compared to the group in whom an expectant approach was taken).

29. Who gets axillary dissection? • Patients with large tumours – T3 or T4 • Patients with confirmed axillary node metastasis • Palpable enlarged axillary lymph nodes • Suspicious axillary nodes seen on ultrasound examination of the axilla • Usually confirmed by ultrasound guided FNA cytology

30. The morbidity of axillary dissection: Wound infection Seroma Pain, parasthesia, and numbness in the distribution of the intercostobrachial nerve Frozen shoulder lymphoedema

31. Is sentinel node biopsy superior to axillary dissection with respect to complications? • ACSOG Z0011, ALMANAC both show that there is significantly less morbidity after SLNB when compared to ALND (70% adverse effects v 25% overall) • Inconsistent application of protocols and incomplete data capture was a problem in both of these two studies as it has been in other published studies.

32. Ductal Carcinoma In Situ A condition in which presumably malignant cells proliferate within lactiferous ducts with no evidence of invasion through the basement membrane Heterogeneous pathology with highly variable appearance, biology and behaviour Represents around 20% of the caseload Is largely a disease entity of the mammographic era The approach to surgical management is somewhat different

33. What surgery is offered? Mastectomy +/- reconstruction is a commonly utilised option • Best for large lesions, and multifocal/multicentric lesions • Low local recurrence rate (1%-2%) • In most instances obviates the need for XRT • For many patients it represents too much treatment • Psychosocial issues: • For some the reassurance of a high probability of cure is reassuring • For others there is the psychological morbidity of what might be perceived as a mutilating operation

34. What surgery is offered: Wide local excision Wide local excision alone is associated with a high local recurrence rate (NSABP 20.9% at 5years) May be acceptable in selected patients ie small, non high grade lesions with good margins (>10mm) Wide local excision plus XRT lower local recurrence rates (8%-10% at 5years) About half of the local recurrences are invasive

35. What margins are required in BCT for DCIS? A vexed question in this condition because of the high incidence of multifocality and multicentricity which makes pathological assessment of margins difficult NZ guideline – margin should be >2mm Ideal is 10mm Involved margins demands further surgery

36. Management of the Axilla in DCIS • Theoretically DCIS should not involve nodes • In practice microinvasion or even overt invasive disease in another part of a lesion may result in nodal metastasis in up to 25% of lesions diagnosed as DCIS on work up • Risk factors: • Large tumour • High grade • Palpable tumour • Mammographic density

37. Should patients with a preoperative diagnosis of DCIS have sentinel node biopsy? Indications for sentinel node biopsy in DCIS: Large lesion High grade Palpable tumour Mammographic density Patient is having a mastectomy

38. Who gets what operation? 40 years ago - MASTECTOMY and AXILLARY DISSECTION Today – Multi disiplinary approach with surgery tailored to the needs of the patient and her condition and integrated with radiotherpy and systemic therapies Thankyou