Breast Cancer

27/05/2013 by admin | Oncology

 

  1. 2nd most common cancer (1st?!) in women
  2. 24,000 women diagnosed/yr/UK. 15,000 dying/yr/UK
  3. By 80yo – lifetime risk of BC is 1:9
  4. Aetiology:
    1. o Oestrogen exposure: particularly unopposed oes (no progesterone), so early menarche, late menopause, and nulliparity
    2. o Family and personal history: 10% of BC is genetically determined by genes including BRCA-1, BRCA-2, p53, A-T. Also a previous Hx of breast/endometrial/or ovarian cancer indicates a genetically increased risk. Previous benign breast disease and chest irradiation are also RFs
    3. o BRCA-1 (highly increased risk of BC and ovarian cancers) and BRCA-2 (moderately increased risk on BC, less so of OC) – are autosomal dominant and occur in 2% of all women with BC, but in 50-80% of young patients <40yo with a strong FH of breast and ovarian cancer.
    4. o Ataxia-Telangiectasia (A-T) gene is autosomal recessive DNA repair gene, found in 0.5-1% of general population
    5. o High fat consumption and low socioeconomic status
  5. Pathology:
    1. o Adenocarcinoma is most commonly infiltrating ductal
    2. o Lobular/medullary/mucinous/papillary/or tubular carcinomas are rarer.
    3. o BC can also present as Paget’s disease of the nipple (involving nipple and overlying skin = looks like eczema), rarely lymphoma, sarcoma, squamous or clear cell carcinomas.
    4. o Breast adenocarcinomas are graded histologically using: ‘The modified Bloom and Richardson’ scheme (=characterizes aggressiveness and probable behaviour on the basis of tubule formation, nuclear pleomorphism and mitotic rate)
  6. Other important histological findings include:
    1. o Receptor status: BC cells may express oestrogen and/or progesterone receptors. Their presence/absence affects tx.
    2. o Ductal carcinoma in situ (DCIS): malignant cell proliferation within the ducts without stromal invasion , usually unilateral , occasionally multi-focal. Usually detected on mammography. Without tx, 14-30% develop invasive disease.
    1. o Lobular carcinoma in situ (LCIS): proliferation of malignant cells within breast lobules, rarely palpable or visible on mammography. Usually multicentric, bilateral, not premalignant, but rather an indicator of increased risk of BC.
  1. Ix:
    1. o Initial diagnosis:
    2. o Two view mammography (oblique and craniocaudal): not useful in women <40yo – breasts are too radiodense
    3. o Breast USS: useful if a palpable mass. Malignant lesions have indistinct edges. Not useful for screening.
    4. o Fine needle/Tru Cut biopsy: manual or sterotactic
  2. Staging:
    1. o The modified Bloom and Richardson scheme (Nottingham scheme) = histopathological grading
    2. o TNM staging = to assess extent of cancer in patients body
    3. o Routine haematological and biochemical screening (inc LFTs, and serum Ca), CXR, USS liver, isotope bone scan.
  3. Tx:
    1. o Surgery:
    2. Remove tumour and gain staging/prognostic information from the tumour and axillary nodes
    3. Modified radical mastectomy – indicated for larger (>4cm) multi-centric tumours or if there is extensive DCIS or skin involvement. Extensive axillary dissection reduces the risk of axillary recurrence
    4. Breast conserving ‘lumpectomy’ with post-op RT
    5. Local excision of the tumour with a histological confirmed normal margin, combined with post-op radical RT (should give results similar to total mastectomy)
    6. Axillary node sampling: no benefit to local control unless combined with post-op RT
    7. Axillary node clearance/dissection: removal of all LNs. Provides good control, no RT required and maximum prognostic information obtained about number of LNs with mets.
    8. o Radiotherapy:
    9. Adjuvant RT to remnants of cancer reduce risk of local recurrence, following breast conserving surgery
    10. RT to axilla given if there were positive nodes (+mets). Not to be done if full LN discetion was completed as adds very little and runs high risk of lymphoedema
    11. Adjuvant systemic therapy: 30-50% with resectable BC subsequently dis of their disease – suggesting micromets were present at diagnosis. Subsequent adjuvant RT reduces risk or relapse
    12. o Endocrine therapy: tamoxifen (an anti-oestrogen) reduces risk or relapse. It is given for 5 years after which modest risks of continuing outweigh any benefit. Similar hormonal manipulations can also be obtained with LHRH agonists or oophorectomy
  4. CT: most patients with moderate to high risk disease (ie NOT <1cm, low grade, node negative), benefit from adjuvant CT. Benefit in both pre- and post-menopausal women. Combined CT is used.
  5. Follow –up: used to detect recurrence, manage tx-related toxicity, and screen for new primary lesions. Good time to provide psychological support. The cancer risk to the second breast is increased x 4. Mammography should be performed on a yearly basis.
  6. Locally advanced BC:
    1. o Defined as tumours >5cm, or showing signs of skin or chest wall invasion (‘fixed’) or inflammatory BC (‘erythematous’ with lymphatic permeation).
    1. o A response to primary tx with endocrine therapy (tamoxifen) and CT may facilitate surgery and RT and may allow breast-conserving surgery
  1. Metastatic BC:
    1. o 1st line = Tamoxifen
    2. o 2nd line = aromastase inhibitors (=anastrozole) or progesterones
    3. o Oestrogen suppression can be obtained with surgical or radiation-induced ovarian ablation or with LHRH antagonsists
    4. o CT should be considered in young, rapidly progressive, oestrogen receptor (ER) negative, visceral disease, relapsing disease. Regimen = same as in adjuvant setting (=anthracycline/cyclophosphamide/methotrexate/5FU/taxanes)
    5. o The taxanes (=docetaxel and paclitaxel) are v active and are 2nd line.
  2. HRT:
    1. o Slightly increases risk of BC and should be avoided in patients with node-positive BC.
  3. Tx summary:
    1. o LN negative = tamoxifen and RT
    2. o LN positive but ER/progesterone negative = CT = anthracycline/cyclophosphamide/methotrexate/5FU/taxanes
    3. o LN positive and ER/progesterone sensitive = anti-oestrogens, oophorectomy, or LHRH anologues, aromatase inhibitors, progesterone
    4. o LN positive and aggressive clinical course (regardless of ER status) = CT = anthracycline/cyclophosphamide/methotrexate/5FU/taxanes 
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