Most common female malignancy & 2nd most common cause of CA death in the United States

Approx. 225000 new cases in 2012 & approx. 40000 D due to breast CA

Approx. 1 million new cases diagnosed annually worldwide

↑ incidence but ↓ mortality in past few decades

Strongest: Female gender, ↑ age

↑ estrogen: Early menarche, late menopause, late parity, or nulliparity (NEJM 2006;354:270); prolonged HRT (RR 1.24 after 5.6 y, JAMA 2003;289:3243); no ↑ risk w/OCP use (NEJM 2002;346:2025)

Benign breast conditions: ↑ risk: Proliferative features (ductal hyperplasia, papilloma, radial scar, sclerosing adenosis); atypia (atypical ductal or lobular hyperplasia); dense breast tissue (↓ mammographic Sn); no ↑ risk: Cysts, fibroadenoma, columnar changes (NEJM 2005;352:229)

Other: ↑ BMI, FHx (see below), smoking, alcohol consumption, prior thoracic irradiation

Modified Gail model: Multivariate logistic regression model (www.cancer.gov/bcrisktool/)

BRCA 1/2 Mt: 56-84% lifetime risk of breast CA

Other familial/hereditary breast CA: TP53, PTEN, ATM gene Mt

Mammography: 20-30% ↓ in breast CA mortality (<50 y smaller absolute benefit) (Lancet 2001;358:1340 & 2002;359:909; Annals 2002;137:347; Lancet 2006;368:2053)

Annual breast MRI: For high-risk pts – BRCA Mt or unknown BRCA status & 1st-degree relative of BRCA carrier, lifetime risk ≥20%, chest irradiation between age 10 & 30 y, genetic syndrome (JAMA 2006;295:2375 & CA 2007;57:75)

Stage 0: Carcinoma in situ; Stage IA: T1 (tumor ≤ 2 cm), N0; Stage IB: T1N1mi (micrometastasis to LN > 0.2 mm but ≤ 2 mm); Stage IIA: T2 (tumor 2-5 cm), N0 or T1N1 (1-3 axillary nodes); Stage IIB: T2N1 or T3 (tumor >5 cm), N0; Stage IIIA: N2 (4-9 axillary nodes) or T3N1; Stage IIIB: T4 (direct extension to CW and/or skin or inflammatory); Stage IIIC: N3 (≥10 axillary nodes or any infraclavicular or ipsilateral supraclavicular nodes); Stage IV: Distant mets

Invasive: Ductal (IDC) – most common of invasive carcinomas; lobular (ILC)

Molecular & Receptor classification (JCO 2010;28:1684)

Mastectomy = lumpectomy + breast RT in OS, ie, BCS (NEJM 2002;347:1227-1233)

BCS is 1° tx for Stage I & Stage II.

Sentinel LN bx for (1) clinically negative axillary exam or (2) negative axillary FNA or core bx

Axillary LND for (1) >2 positive sentinel nodes, (2) clinically palpable nodes, or (3) positive axillary FNA or core bx

RT: Postmastectomy CW RT for ≥4 + LNs (1-3 + LNs send to radiation oncologist to decide), tumor >5 cm, Stage III, or + surgical margins: ↓ locoregional recurrence & ↑ survival (Lancet 2005;366:2087)

Consider regional RT after BCS for 1-3 + LNs (MA.20 JCO 2011;29(18_suppl):LBA1003)

Give chemotherapy to high risk – biologically (HER2 +, triple negative) or histologically (node-positive) for “most” pts to eradicate occult micrometastatic disease

Computer-based risk model: Adjuvant. Online (www.adjuvantonline.com) determines risk of recurrence based on age, comorbidities, tumor size/grade, hormone receptor status, nodal status; does not account for HER2 status (JCO 2001;19:980)

OncotypeDX: 21-gene signature RT-PCR assay to calculate RS – predicts 10-y distant recurrence rate; low (RS < 18) 6.8%; intermediate (RS 18-30) 14.3%; high (RS ≥ 31) 30.5%. Trials assessing chemo benefit in intermediate group based on Oncotype DX: TAILORx trial (completed) for node (−) & RxPONDER trial (ongoing) for postmenopausal pts w/1-3 (+) nodes

Pts w/ER+, LN−, & low RS derive min. benefit while pts w/high RS have improved DFS w/adjuvant chemotherapy (NSABP B20 JCO 2006;24:3726)

MammaPrint: 70-gene signature to catergorize into 2 groups – good or poor prognosis irrespective of ER status; study ongoing (MINDACT Lancet 2005;365:671)

CMF (Cyclophosphamide, MTX, & fluorouracil) ↑ OS at 30-y follow-up (RR of D = 0.79, p = 0.04) compared to no chemotherapy after surgery (BMJ 2005;330:217); not recommended for high-risk disease

↑ DFS & OS w/anthra (anthracycline) containing regimens > CMF (EBCTCG Lancet 2005;365:1687)

↑ DFS & OS when taxane added to anthra-based regimens (EBCTCG Lancet 2012;379:432; CALGB 9344 JCO 2003; NSABP B-28: JCO 2005;23:3686)

Standard Chemo Options for High-risk Pts:

Nonanthra regimens

Premenopausal: ↓ breast CA mortality w/tam (Tamoxifen) – 31% ↓ × 5 y (NEJM 1998;339:1609) & 48% ↓ × 10 y & only slight ↑ DVT/PE & endometrial CA (ATLAS Lancet 2012)