Breast Cancer Steven Jones, MD

Mammary Gland Anterior view Breast Anatomy Parasternal (internal thoracic) nodes Subclavian (apical axillary) nodes Interpectoral (Rotter’s) nodes Central axillary nodes Brachial (lateral axillary) Subscapular (posterior axillary) Pectoral (anterior axillary) Breast Anatomy

Mammary Gland Anterior view Breast Anatomy Areola Lobar/Lactiferous duct Lobular duct Breast Anatomy Lobule Ampulla Nipple Areola gland Fat Areola

Lobar/Lactiferous Duct Cross Section

Lobar/Lactiferous Duct Cross Section Atypical Ductal Hyperplasia (ADH) Excess growth within the duct includes abnormal or atypical cells. The presence of this condition increases the risk of developing breast cancer.

Lobar/Lactiferous Duct Cross Section Ductal Carcinoma In Situ (DCIS) The entire duct may be filled with abnormal, atypical cells. This condition is actually an early breast cancer.

Cancer cells that break out of the duct and invade the breast tissue. Lobar/Lactiferous Duct Cross Section Invasive Ductal Carcinoma (IDC) Cancer cells that break out of the duct and invade the breast tissue.

Excess growth in the lobules Lobular Hyperplasia Lobular Hyperplasia Excess growth in the lobules Atypical Lobular Hyperplasia Atypical lobular hyperplasia may also develop. If atypical lobular hyperplasia progresses in severity a condition referred to as Lobular Carcinoma In Situ (LCIS) may develop.

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

Breast Cancer Causes Hormonal factors – early menarche, late menopause, age of 1st pregnancy, HRT with progesterone Environment, lifestyle, and diet – ionizing radiation increase risk

Breast Cancer Risks Gender – 1% male Age - < 30 – rare ; risk rises sharply after 40 Personal Hx – 0.5-1% per yr in contra breast Family Hx- 20-30% of Br Ca have + fm hx; only 5-10% have an inherited mutation

Breast Cancer Risks Benign Breast disease – Atypical ductal hyperplasia – 4.5-5.0 RR Lobular Carcinoma in Situ – 5.4-12.0 RR, 1% per year.

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

High Risk Patients Gail model Chemo prevention Increased surveillance

Report Organization 1 2 3 4 5 Category Assessment Recommendations 1 2 3 4 5 Incomplete assessment Additional imaging evaluation Negative Benign finding BI-RADS™ Probably benign Short interval follow-up Suspicious Biopsy should be considered Highly suggestive of malignancy Appropriate action to be taken

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

Open Surgical Biopsy Biopsy Options Performed in the Operating Room An incision is made in the breast and a large tissue sample is cut and removed In some cases, a wire is inserted into the breast to aid in localizing the abnormality Possible scarring and disfiguration that can interfere with future mammograms More costly than other biopsy methods Biopsy Options

Fine Needle Aspiration (FNA) Can be performed in an outpatient setting or doctor’s office No anesthesia No sutures Several needle insertions to collect fluid and/or cellular material Cyst aspiration for fluids Unable to mark biopsy site Biopsy Options

Core Needle Biopsy Local anesthesia No sutures Can be performed in an outpatient setting or doctor’s office Local anesthesia No sutures 4 – 6 needle insertions to collect a sufficient amount of breast tissue for an accurate diagnosis Unable to mark biopsy site Biopsy Options

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

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

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

Systemic Therapy Cytotoxic chemotherapy Hormonal therapy – 50% reduction of recurrence, 26% reduction in mortality Targeted therapy - Herceptin – 50% reduction of recurrence.

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

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 downstage to allow conversion from mastectomy to BCS

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

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