Staging

• Anatomic: tumor size, chest wall invasion, axillary LN mets (strongest prognostic foctor)

• Histopathologic: type (little prognostic relevance) & grade; lymphatic vascular invasion

In situ carcinoma: no invasion of surrounding stroma Ductal (DCIS): T risk of invasive cancer in ipsilateral breast ( 30% 10 y) Lobular (LCIS): marker of ? risk of invasive cancer in either breast ( 1% y) Invasive carcinoma: infiltrating ductal (70-80%); invasive lobular (5-10%); tubular.

medullary, and mucinous (10%. better prognosis); papillary (1-2%); other (1-2%) Inflammatory breast cancer (see above): not a histologic type but a clinical reflection of tumor invasion of dermal lymphatics; very poor prognosis Paget disease: ductal cancer invading nipple epidermis • associated mass

• Biologic: estrogen and progesterone receptor (ER PR) status; HER2 neu overexpression

4 basic subtypes include: luminal A (ER© HER2 >). luminal B (ER© HER2©), basal-like or "triple negative" (ERG PR0Her2O). and ERGHER2©

• Bone marrow micrometastases associated w 2x t risk of death (nejm 200s;353:793)

• Recurrence score (multigene RT-PCR assay) may be sent to help predict recurrence risk in node >. ER© PtS (N£*M 2004:351:2817 i 2006 355 560)

Stage

Simplified Staging System for Breast Cancer

Characteristics Description

5-y surv

Tumor -2 cm or mobile axillary nodes

Operable locoregional

90% 80%

IIB

Tumor -5 cm

65%

IIIA

Internal mammary or fixed axillary nodes

Locally advanced

50%

IIIB

Direct extension to chest wall or skin

Inoperable

45%

IIIC

Infraclavicular or supraclavicular nodes

locoregional

40%

IV

Distant metastases

Metastatic

• Local control: surgery and radiation therapy (RT)

Breast<onserving lumpectomy • breast RT • axillary node dissection (ALND) is equivalent to mosteaomy • ALND {nejm 2002:347.1227.1233); contraindications: multicentric disease, diffuse microcalcifications. prior RT. pregnancy. ? tumor 5 cm

Radiation therapy (RT) after mastectomy for -4 © LN. tumor 5 cm or (f surgical margins i locoregional recurrence and T survival (lancer 2005:366:2087)

• Systemic therapy: chemotherapy and other adjuvant therapy

Osmotherapy, anthracycline-based AC (adriamycin cyclophosphamide) taxanes (paditaxei or docctaxel) for advanced disease, node • tumors (Nejm 2005:3512302), or high-risk node tumors (eg. HER2 •). Litde benefit of adding taxanes in ER • tumors.

Biologic trastuzumab (Herceptin; anti-HER2 neu mAb) T survival in HER2 • tumors (15-20%).

but • cardotoxicity W anthracydines (nejm 2005.353:165*1673: Lone« 2007:369:29) lapatinib (tyrosine kinase inhib. of HER2 & EGFR): delays progression in Pts who have failed trastuzumab (nejm 2006355:2733)

Hormonal (in ER PR • or unknown status) tamoxifen: 41% ; recurrence and 34% i breast cancer mortality in postmenopausal

PtS (tone« 2005:365:1687) aromatasc inhibitors (Al) (anastrozole. letrozole. exemestane): 18% I recurrence

C w tamoxifen in postmenopausal PtS (Lancet 2005.365:60: NEJM 2005:353:2747) options include upfront Al or tamoxifen ■: 2-3 y followed by Al (lancet 2007:36*559) 2nd-line: ovarian ablation with LHRH agonists (goserelin) or oophorectomy if premenopausal; pure antiestrogens (fulvestrant) if postmenopausal ovarian ablation * Al or tamoxifen for premenopausal women is under study

Treatment of Carcinoma in situ and Invasive Carcinoma of the Breast

LCIS

Close surveillance t chemoprevention; ? prophylactic bilat. mastectomy

DCIS

Mastectomy or lumpectomy « RT: ALND not indicated; • chemoprevention {NEJM 2004:350:1430)

• Adjuvant chemo if I risk: tumor 1 cm or 1 LN or ER PR 1 (lancet 1998:352*30) + Hormonal therapy for ER PR © (or unknown status) tumors

• Trastuzumab if HER2' and tumor 1 cm or © LN

III

Neoadjuvant chemo — surgery • RT adjuvant chemotherapy

• Hormonal therapy for ER PR © (or unknown status) tumors

• Trastuzumab if HER2<?'

IV

ER PR r: hormonal therapy * chemotherapy ER PR . HER2- : chemo « trastuzumab ER PR G. HER2 : chemotherapy

Bony mets: bisphosphonates i skeletal complic. (NEJM 1998:33*357)

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