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

2.  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 History of Breast Cancer Treatment

3.  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 The Modern Era (1)

4. 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 The Modern Era (2)

5.  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 1.Extirpation of the primary tumour 2.Removal of involved regional lymph nodes  Relative contraindications to surgery:  Advanced age and frailty  Advanced disease Who gets surgery?

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

7.  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 Mastectomy:

8.  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 Indications for simple mastectomy:

9. 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% Breast Conserving Treatment:

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

11.  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) Good control of the primary tumour:

12. 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 How much is enough?

13.  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 Contraindications to BCT

14.  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 eg angiosarcoma (1 in 476 patients)  Risk of salvage mastectomy Morbidity of BCT:

15. 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 Is there a survival equivalence between BCT and Mastectomy in STI-II cancers:

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

17.  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. Why operate on the axilla?

18.  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 Who gets axillary surgery?

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

20.  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 Sentinel lymph node biopsy

21.  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 Who gets Sentinel node biopsy?

22.  Combined technique of vital blue dye and radioisotope.  Technitium labelled sulphur 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. Sentinel node biopsy – principles

23. 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 Sentinel node biopsy principles

24.  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% How reliable is sentinel node biopsy?

25.  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 Management of the axilla where there has been a positive sentinel node biopsy

26.  RCT – Surgery v XRT  Five year follow up  Results:  Local recurrence0.54% v 1.03%  Disease free survival86.7% v 82.7%  Overall survival93.3% v 92.5%  Lymphoedema28% v 14% EORCT AMAROS Study ASCO 2013 – Emeil Rutgers

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

28.  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). Axillary dissection – why we do it

29.  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 Who gets axillary dissection?

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

31.  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. Is sentinel node biopsy superior to axillary dissection with respect to complications?

32.  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 Ductal Carcinoma In Situ

33. 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 What surgery is offered?

34. 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 What surgery is offered:

35.  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 What margins are required in BCT for DCIS?

36.  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 Management of the Axilla in DCIS

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

38.  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 Who gets what operation?