5Lobar/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.
6Lobar/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.
7Cancer cells that break out of the duct and invade the breast tissue. Lobar/Lactiferous Duct Cross SectionInvasive Ductal Carcinoma (IDC)Cancer cells that break out of the duct and invade the breast tissue.
8Excess growth in the lobules Lobular HyperplasiaLobularHyperplasiaExcess growth in the lobulesAtypical Lobular HyperplasiaAtypical lobular hyperplasia may also develop.If atypical lobular hyperplasia progresses in severity a condition referred to as Lobular Carcinoma In Situ (LCIS) may develop.
9Epidemiology of Breast Cancer 232,340 American women diagnosed each year.39,620 die each year from the diseaseLifetime risk through age 85 is 1 in 8, or 12.5%2nd leading cause of cancer deaths among US women, after lung cancerLeading cause of death among women age 40-55
10Breast Cancer CausesHormonal factors – early menarche, late menopause, age of 1st pregnancy, HRT with progesteroneEnvironment, lifestyle, and diet – ionizing radiation increase risk
11Breast Cancer Risks Gender – 1% male Age - < 30 – rare ; risk rises sharply after 40Personal Hx – 0.5-1% per yr in contra breastFamily Hx % of Br Ca have + fm hx; only 5-10% have an inherited mutation
12Breast Cancer RisksBenign Breast disease – Atypical ductal hyperplasia – RRLobular Carcinoma in Situ – RR, 1% per year.
13CRITERIA FOR REFERRAL FOR GENETIC COUNSELING OF INDIVIDUALS AT INCREASED RISKFOR BRCA1/2-ASSOCIATED HEREDITARY BREAST CANCERa,bPersonal history of breast cancer diagnosed≤ 40Personal history of breast cancer diagnosed≤ 50 and Ashkenazi Jewish ancestryPersonal history of breast cancer diagnosed≤ 50 and at least one ﬁrst- or second-degree relative with breast cancer ≤50and/or epithelial ovarian canceraClose 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)
14Continued….Personal history of breast cancer and two or more relatives on the same side of the family with breast cancer and/or epithelial ovarian cancerPersonal history of epithelial ovarian cancer, diagnosed at any age, particularly if Ashkenazi JewishPersonal history of male breast cancer particularly if at least one ﬁrst- or second-degree relative with breast cancer and/or epithelial ovarian cancerRelatives of individuals with a deleterious BRCA1/2mutation
21Open Surgical Biopsy Biopsy Options Performed in the Operating Room An incision is made in the breast and a large tissue sample is cut and removedIn some cases, a wire is inserted into the breast to aid in localizing the abnormalityPossible scarring and disfiguration that can interfere with future mammogramsMore costly than other biopsy methodsBiopsy Options
22Fine Needle Aspiration (FNA) Can be performed in an outpatient setting or doctor’s officeNo anesthesiaNo suturesSeveral needle insertions to collect fluid and/or cellular materialCyst aspiration for fluidsUnable to mark biopsy siteBiopsy Options
23Core Needle Biopsy Local anesthesia No sutures Can be performed in an outpatient setting or doctor’s officeLocal anesthesiaNo sutures4 – 6 needle insertions to collect a sufficient amount of breast tissue for an accurate diagnosisUnable to mark biopsy siteBiopsy Options
24National Surgical Adjuvant Breast Project Radical mastectomyvsSimple mastectomy with axillary irradiationSimple mastectomy with delayed axillary dissectionStarted in 1971, 1665 patients enrolled, 25 year follow upNo difference in disease free or overall survival
25Breast 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
26NSABP B-06Total mastectomy vs lumpectomy vs lumpectomy plus irradiationNo significant difference in survival14.3% recurrence in lumpectomy plus radiation group at 25 years39.2% recurrence in lumpectomy without radiation group at 25 years
27Conclusion NSABP B-06Lumpectomy 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.
28Contraindications for Breast Conserving Therapy Absolute:Prior radiation to the breast or chest wallPregnancyMuticentric diseaseDiffuse, malignant appearing microcalcifications
29Relative Contraindications for BCT History of collagen vascular diseaseVery large tumor > 5cmsVery large breasts
30Axillary Biopsy and Control 1. StagingIn the absence of distant mets number of positive lymph nodes is the most important prognostic factor.2. Regional ControlIn clinically negative axilla, axillary dissection reduces local occurrence from 20% to 3%3. Small survival advantage (3-5%)
31Sentinel Lymph Node Technetium labeled sulfur colloid Isosulfan blue (lymphazurin 1%)Combined – 97% ID’ed; 6% false negative1% anaphylactic reaction to blue dye
32Sentinel Lymph Node Technetium labeled sulfur colloid Isosulfan blue (lymphazurin 1%)Combined – 97% ID’ed; 6% false negative1% anaphylactic reaction to blue dye
33Systemic Therapy Cytotoxic chemotherapy Hormonal therapy – 50% reduction of recurrence, 26% reduction in mortalityTargeted therapy - Herceptin – 50% reduction of recurrence.
34ALGORITHM FOR ADJUVANT SYSTEMIC THERAPY FOR BREAST CANCER ER- and/or PR-PositiveER- and PR-NegativeERBB2 negativeaEndocrine therapy± chemotherapydepending on riskChemotherapyERBB2 positiveEndocrine therapy+ chemotherapy+ trastuzumabchemotherapy+ trastuzumabER, estrogen receptor; PR, progesterone receptoraFormerly HER-2
35NSABP B-18 Started 1988; 1523 pts, 4 cycles AC 80% overall response 13% pathologic complete responseNo difference in overall survivalOnly 3% had progression of disease25% downstaging at axilla30% of women will downstage to allow conversion from mastectomy to BCS
36IndicationsTo downstage women with large tumors that cannot undergo BCS with good cosmetic result – 30% of women will downstage.Early initiation of systemic treatmentIn vivo assessment of response, good biological modelLess radical surgery needed
37Tulane surgery:“ tough as the marines except the marines get to eat”