DESCRIPCIÓN FUNCIONAL Y CONSTRUCTIVA

Options can be divided into aims of control (with either curative of palliative intent):

(a) Locoregional control:

Surgery (WEAC vs SMAC) Radiotherapy

(b) Systemic control: (size >10mm; <70YO) Chemotherapy

Hormonal therapy Targeted therapy Surgery

1. Preparing for operation:

- Anaesthesia workup and necessary imaging. Mark out the site

- Psychological counselling, consent taking, discuss breast reconstruction 2. Wide excision (breast-conserving surgery; standard of care)

- Removal of tumour with clear margins, while achieving good cosmetic result - Criteria: [Nodal status does not influence decision for WE or SM]

1. Only 1 tumour, not multicentric/ multiple DCIS/ LCIS (multifocal) unless same quadrant 2. No metastatic disease

3. Appropriate tumour size-to-breast ratio (to achieve good cosmetic result) - not about T staging anymore 4. Previously conserved breast

5. Patient must agree to post-operative radiotherapy (daily RT in hosp) 6. No CI to RT

a. not PREGNANT (the only absolute CI)

b. No CTD –underlying inflammation may get worse c. No previous RT to the chest

- Results: overall survival at 25 years for WEAC comparable to SMAC, with Slightly higher local recurrence rates (for WEAC: 1% per year, 4% in 5 years)

- Higher risk in younger patients as cancer tends to be more aggressive

Aim of adjuvant therapy:

1. Prevent local recurrence a. RT

b. ± CT, HT, TT 2. Eradicate micrometastasis

a. CT, HT, TT b. ± RT

Reduces recurrence by 1/3; but if recurs have poor prognosis

2. Simple mastectomy (if any CI to Wide excision)

- Removal of breast tissue, nipple-areolar complex, and overlying skin - Ind

1. CI to wide excision

2. Patient prefers to remove entire breast

3. Need to remove nipple (WE cannot give good cosmesis)

- Lower rates of local recurrence; similar long term prognosis as WE (Italian trial) - If done for DCIS, dont need to give adjuvant therapy

3. Axillary clearance

- Purpose of removal: NODAL STAGING (for prognostication) - does not confer survival benefit - Routinely be done in (1) Clinically palpable LN / detected on US (2) BrCA >/= T2 (5cm)

- Not required for DCIS (theoretically cancer cells are confined to the breast) if diagnosed on excision biopsy / wide excision. Recommended if diagnosed on Core biopsy (sampling error).

- Complications: see below

- Sentinel lymph node (SLN) biopsy (SLN) is a new standard of care Only in Early CA (</= 5cm)

Principle: the sentinel lymph node, being the first lymph node draining the breast, is representative of the rest of the axilla; if the SLN is negative for tumour cells, then the rest of the axillary nodes should be negative as well

o Solitary internal mammary LAD is rare

Use of blue dye (isosulphan blue, methylene blue) or radioactive isotope (Tc-99 sulphur colloid or colloidal albumin) injected in the area of the breast just before surgery concentrates in the first lymph node (sentinel node) that drains the breast after 5mins

During the op, look for the SLN by colour, or using a Geiger-Muller counter to detect the node with highest radioactivity. Send node for frozen section (FS)

If -ve do not clear axilla; if +ve, perform axillary clearance

False –ve rate of SLN Bx <5%; false –ve rate of FS ~ 33% if so, re-explore if histology +ve and do AC No difference in axillary recurrence between AC vs SLN biopsy

4. Palliative surgery

- Palliative mastectomy for symptoms (bleeding, fungating, infected tumour) - 'toilet mastectomy' - Surgery at other sites:

Fixation of pathological fractures,

decompression of spinal cord compression, surgical excision of brain metastases 5. Breast reconstruction

- Safe, can be done during breast surgery or at a later time

- No delay in subsequent treatment and no increase in rates of relapse - Cx: abnormal sensation of breast, unable to breastfeed

- Options:

(i) Prosthesis – 6 wks post-op

(ii) Muscle flap from rectus abdominis or latissimus dorsi Complications of surgery

Early Haemorrhage (POD1)

Wound Infection (POD3)

Seroma formation (accumulation of serum) in 50% Flap ischemia

Late Cosmetic deformity

Complications of Axillary Clearance:

- Lymphoedema – RT to axilla is contraindicated with AC as it worsens oedema - Cellulitis – even in minor trauma, due to lymphoedema. Need to clean even minor

wounds with antiseptic solution + prophylactic ABx vs staphstrep - Shoulder stiffness – require physiotherapy

- Intercostobrachial nerve transection – numbness over inner aspect of arm.

Other forms of mastectomy (modified raical, radical or extended radical mastectomy) are not performed anymore.

Radiotherapy

1. Adjuvant: to decrease local recurrence rate - (a) Usually done 6/52 after WE

- (b) High risk of local recurrence: >/= 5cm OR >/= 4 LN +ve

- Targeted at Breast with or without internal mammary, infra/supraclavicular LN (Axillary LN are tackled during Surgery) - CI: pregnancy, previous RT, patient choice

- Regimen consists of 25 to 30 cycles in total, 1 cycle per day from Mon - Fri over 5-6/52 until max dose (no repeat RT for recurrences) - Cx: radiation injury (e.g. pneumonitis, skin changes), risk of cancers 1 in 2000 in 20yrs

2. Palliative - Brain mets

- Bone mets to painful areas / impending fractures

Chemotherapy (polyCT with 3 drugs is better; 4-6cycles, each over 1/12) - Main purpose: eliminate micrometastasis! 1. Neoadjuvant

(a) Given in Locally advanced breast cancer (stage III) to shrink the tumour before surgical resection (b) To shrink tumors before breast conserving Sx

- 20% achieve complete clinical response (cCR) i.e. tumour is no longer palpable

further 20% will achieve complete pathological response (cPR) i.e. no more tumour cells = good prognosis

- Place clip into tumour before neoadjuvant therapy to guide surgery in case tumour  “disappears”;;  operate  according  to preop staging - Cx: as for CT drug, e.g. mouth ulcers, N/V, hair loss, immunosuppression (main disadvantage pre-op)

2. Adjuvant

- Start 3/52 after surgery; given in stage III / LABC (LN+ve) & in some early breast cancers depending on stage (see below)

- Premenopausal patients tend to have better response to chemotherapy than hormonal therapy (vice versa for postmenopausal patients) - Main active agents: anthracyclines (e.g. doxorubicin, epirubicin) and the taxanes (e.g. paclitaxel, docetaxel)

- Common regimens: AC (anthracycline, cyclophosphamide), FAC (5-FU, anthracycline, cyclophosphamide), CMF (cyclophos, methotrexate, 5-FU)

3. Palliative

- Anthracyclines and taxanes are the mainstay

- Helps to reduce load of disease to alleviate symptoms, increase survival Hormonal therapy

- Used in adjuvant setting to eradicate micrometasis (likewise with CT & TT) - For ER/PR +ve will have 90% response

- Preferred for postmenopausal women as response to hormonal therapy is better

- May render patient postmenopausal for better response to HT via medical ablation with LHRH-a or surgical oopherectomy - Mostly used as adjuvant therapy but can also be used as palliative treatment & preventive treatment in high risk patients

- Also reduces risk in contralateral breast (a) Selective oestrogen receptor modulators (SERMs): Tamoxifen

- 50% reduction in recurrence, 25% reduction in mortality - taken daily for 5 years

- CI: PHx of CVA/DVT, immobile patients

- Side effects: 1. menopausal symptoms (hot flushes, etc),

2. endometrial cancer (0.1% per year), 3. deep vein thrombosis

(b) Aromatase inhibitors: Lanastrazole, letrozole, exemestase

- Inhibit peripheral conversion of testosterone and androstenedione to oestradiol (still present in post-menopausal women)

- Only suitable for post-menopausal patients as use of these agents will cause overactivity of the HPA axis in premenopausal women - Side effects: 1. musculoskeletal pain,

2. osteoporosis! Targeted therapy

- Herceptin (trastuzumab)

- targets Her-2-neu a.k.a. C-erbB2 receptor (an epidermal growth factor receptor [EGFR] that is overexpressed in 18-20% of cancers) - Used in C-erbB2 positive tumours, early or late stage

- Her-2-neu indicates worse prognosis Herceptin improves prog to normal - Side effects of Herceptin: 1. cardiomyopathy & CCF

2. pulmonary toxicity, 3. infusion reactions, 4. febrile neutropaenia

- Avastin (or bevacizumab, targets vascular endothelial growth factor [VEGF] receptor, used in advanced cancer); - Lapatinib (targets Her-1 and Her-2, used in advanced cancers)