Local Management of Invasive Breast Cancer By Steven Jones, MD

Connecting with the patient is the best part of medicine. We’re artists, not engineers

Pathological Variables Luminal A HER2-Positive (IHC) 12 ER-Positive(IHC) 96 Grade III 19 Tumor size> 2 cm 53 Node- positive 52

Pathological Variables Luminal B (%) HER2-Positive (IHC) 20 ER-Positive(IHC) 97 Grade III 53 Tumor size> 2 cm 69 Node- positive 65

Pathological Variables HER2-like (%) HER2-Positive (IHC) 100 ER-Positive(IHC) 46 Grade III 74 Tumor size> 2 cm Node- positive 66

Pathological Variables Basil-like (%) HER2-Positive (IHC) 10 ER-Positive(IHC) 12 Grade III 84 Tumor size> 2 cm 75 Node- positive 40

Epidemiology of Breast Cancer 232,340 American women diagnosed each year. 39,620 die each year from the disease Lifetime risk through age 85 is 1 in 8, or 12.5% 2nd leading cause of cancer deaths among US women, after lung cancer Leading cause of death among women age 40-55

Staging Recommendation prior to primary therapy History and physical Liver function tests Breast imaging: ipsilateral and contralateral breasts Mammogram U/S MRI Axillary imaging

MRI for Local-regional Staging Pros: Cons: Changes surgery 20% Multifocal- 3.6% Multicentric – 4.4% Contralateral – 1.8% With adjuvant therapy local failure low – 6% Too many mastectomies Some data demonstrate no difference in local failure rates

MRI Pre-op Diagnostic dilemma BRCA 1 / 2 known or suspected carriers wishing BCT Occult malignancy presenting with axillary mets

Staging Recommendation Prior to Primary Therapy

CRITERIA FOR REFERRAL FOR GENETIC COUNSELING OF INDIVIDUALS AT INCREASED RISKFOR BRCA1/2-ASSOCIATED HEREDITARY BREAST CANCERa,b Personal history of breast cancer diagnosed≤ 40 Personal history of breast cancer diagnosed≤ 50 and Ashkenazi Jewish ancestry Personal history of breast cancer diagnosed≤ 50 and at least one first- or second-degree relative with breast cancer ≤50and/or epithelial ovarian cancer aClose relatives of individuals with the history mentioned in the table are appropriate candidates for genetic counseling. It is optimal to initiate testing in an individual with breast or ovarian cancer prior to testing at-risk relatives. bCriteria modified from NCCN (109)

Continued…. Personal history of breast cancer and two or more relatives on the same side of the family with breast cancer and/or epithelial ovarian cancer Personal history of epithelial ovarian cancer, diagnosed at any age, particularly if Ashkenazi Jewish Personal history of male breast cancer particularly if at least one first- or second-degree relative with breast cancer and/or epithelial ovarian cancer Relatives of individuals with a deleterious BRCA1/2mutation

Evolution of Breast Cancer “Cancer of the breast spreads centrifugally. It disseminates to bone by way of the lymphatics, not by blood vessels.” Halsted, WS. The results of radical operations for the cure of carcinoma of the breast. Ann Surg 1907; 66:1

Halstedian concept did not apply More extensive surgical procedures did not reduce risk of distant metastasis Identification of small breast cancer by mammography

National Surgical Adjuvant Breast Project Radical mastectomy vs Simple mastectomy with axillary irradiation Simple mastectomy with delayed axillary dissection Started in 1971, 1665 patients enrolled, 25 year follow up No difference in disease free or overall survival

Breast Cancer Multifocality Holland et al. Only 37% of cancers are confined to the primary tumor. 20% have additional cancer within 2 cms. 43% have additional cancer beyond 2 cms. Holland R, Veling S, Mravunac M, et al. Histologic multifocality of Tis, T1-2 breast carcinomas: implications for clinical trials of breast-conserving treatment. Cancer 1985; 56: 979

NSABP B-06 Total mastectomy vs lumpectomy vs lumpectomy plus irradiation No significant difference in survival 14.3% recurrence in lumpectomy plus radiation group at 25 years 39.2% recurrence in lumpectomy without radiation group at 25 years

Conclusion NSABP B-06 Lumpectomy followed by breast irradiation is the appropriate therapy for women with breast cancer, provided that the margins of resected specimens are free of tumor and an acceptable cosmetic result can be obtained.

Contraindications for Breast Conserving Therapy Absolute: Prior radiation to the breast or chest wall Pregnancy Muticentric disease Diffuse, malignant appearing microcalcifications

Relative Contraindications for BCT History of collagen vascular disease Very large tumor > 5cms Very large breasts

Margins Clear: tumor not touching the ink Close: < 1mm – may be a problem with young or extensive intraductal component

ALGORITHM FOR ADJUVANT SYSTEMIC THERAPY FOR BREAST CANCER ER- and/or PR-Positive ER- and PR-Negative ERBB2 negativea Endocrine therapy± chemotherapy depending on risk Chemotherapy ERBB2 positive Endocrine therapy+ chemotherapy+ trastuzumab chemotherapy+ trastuzumab ER, estrogen receptor; PR, progesterone receptor aFormerly HER-2

Radiation Therapy Whole breast with boost to tumor bed standard Accelerated partial breast irradiation Balloon ( Mammosite) Interstitial brachytherapy External beam limited RT Intraoperative limited RT

Post-mastectomy Radiation Early studies showed increased mortality Recent studies show substantial decrease in locoregional recurrence Recent trials show survival benefit 5-8% at > 10 years.

Indications for Post-mastectomy Radiation T3 or T4 tumors Tumors invading skin or muscle 4 or more pos. axillary nodes (Some recommend for 1-3 nodes, depending)

Breast Reconstruction Immediate – skin sparing Delayed immediate – skin sparing Delayed

Skin Sparing Mastectomy Includes areolar (nipple sparing controversial) Excise biopsy incision Radiate positive margins

Axillary Biopsy and Control 1. Staging In the absence of distant mets number of positive lymph nodes is the most important prognostic factor. 2. Regional Control In clinically negative axilla, axillary dissection reduces local occurrence from 20% to 3% 3. Small survival advantage (3-5%)

Sentinel Lymph Node Technetium labeled sulfur colloid Isosulfan blue (lymphazurin 1%) Combined – 97% ID’ed; 6% false negative 1% anaphylactic reaction to blue dye

Locally Advanced Cancer Large primary tumors (>5cm) especially with pos. nodes Tumors with skin or chest wall involvement Tumors with fixed or matted axillary nodes or ipsilateral subclavian or supraclavicular lymph nodes Most have been present for months or years but treatment has been delayed

Inflammatory Breast Cancer Rapid onset and progression over weeks to months Skin often discolored red to purple Skin thickened or peau d’ orange Induration Invasion of dermal lymphatics is a common feature but not required or sufficient for a diagnosis 1-5% of breast cancers

Neoadjuvant Chemotherapy Preoperative Systemic Therapy aka Preoperative Systemic Therapy Primary Chemotherapy

NSABP B-18 Started 1988; 1523 pts, 4 cycles AC 80% overall response 13% pathologic complete response No difference in overall survival Only 3% had progression of disease 25% downstaging at axilla 30% of women will downsize to allow conversion from mastectomy to BCS

Indications To downsize women with large tumors that cannot undergo BCS with good cosmetic result – 30% of women will downsize. Early initiation of systemic treatment In vivo assessment of response, good biological model Less radical surgery needed

Pre-operative Endocrine Therapy Best for large low grade ER pos. tumors in post menopausal women Response times 3 months or longer Greater response with aromatase inhibitors compared with tamoxifen Under-utilized in the US

Tulane surgery:“ tough as the marines except the marines get to eat”