Introduction Epidemiology breast cancer is the most common cancer and second most common cause of death in adult women Risk factors BRCA1 and BRCA2 mutations associated with multiple / early onset breast and ovarian cancer other genetic relationships RAS oncogene gain of function overexpression of estrogen/progesterone receptors overexpression of erb-B2 (HER-2, an EGF receptor) Li-Fraumeni associated TP53 loss increasing age smoking breast cancer in first degree relatives or mother with breast cancer history of contralateral breast cancer history of endometrial cancer also an estrogen induced cancer increased exposure to estrogen obesity nulliparity early menarche (<11 y.o.) late menopause (>50 y.o.) late first pregnancy (>30 y.o.) atypical ductal hyperplasia Classification Ductal carcinoma in situ (DCIS) arises from progression of ductal hyperplasia non-palpable mass seen most often on mammography due to microcalcifications histology shows filled ductal lumen without basement membrane penetration subtypes comedocarcinoma ductal carcinoma with caseous necrosis at the mass center Paget's disease extension of DCIS into lactiferous ducts and skin of nipple eczematous patches on nipple histology shows Paget cells large cells in epidermis with clear halo also seen on vulva Invasive/infiltrating ductal carcinoma worst and most invasive most common type firm, fibrous, "rock-hard" mass histology shows small, glandular, duct-like cells with stellate morphology subtypes tubular carcinoma histology well-differentiated tubules that lack myoepithelial cells mucinous carcinoma histology carcinoma with abundant extracellular mucin Lobular carcinoma in situ (LCIS) non-palpable mass often bilateral histology shows distended lobules with neoplastic cells without BM penetration Invasive lobular often multiple and bilateral histology shows orderly row of cells Medullary associated with BRCA1 and ER/PR negativity histology shows fleshy, cellular, lymphatic infiltrate Inflammatory poor prognosis (50% survival at 5 years) histology shows dermal lymphatic invasion by tumor peau d'orange seen on exam see below Presentation Symptoms often asymptomatic breast lump most commonly in upper-outer quadrant nipple discharge Physical exam firm immobile, painless lump some skin changes redness, ulcerations, edema, and nodularity axillary lymphadenopathy in more advanced cases breast skin edema with dimpling (peau d' orange) represents obstruction of the lymphatics by cancer Evaluation Fine needle aspiration can identify whether mass is solid or cystic can also retrieve sample for cancer diagnosis Estrogen/Progesterone receptor assays most often positive in post-menopausal cancers low estrogen state after menopause results in upregulation of receptors positivity confers better prognosis with more effective therapeutics Sentinel lymph node biopsy if negative high likelihood no other nodes in group are involved if positive there is 1/3 chance other nodes in group are involved Treatment Surgery breast conservation resection resection of tumor with margins sentinel node biopsy radiation modified radical mastectomy resection of nipple, entire breast, pectoralis minor, and level I-II axillary nodes level III axillary nodes removed if involved complications long thoracic nerve damage results in winged scapula lymphedema Prognosis, Prevention, and Complications Prognosis lymph node involvement is the single most important prognostic factor TNM staging extranodal metastases has more significance than lymph node metastasis Prevention mammography effective screening tool except in young woman dense breast tissue in young woman interferes with specificity and sensitivity most effective in postmenopausal patients because of less glandular breast identifies microcalcifications or moderate sized masses all woman > 40 should have mammograms