Breast Cancer Dr. Andres Wiernik 2017
Agenda: The Facts! (Epidemiology/Risk Factors) Biological Classification/Phenotypes of Breast Cancer Treatment approach Local Systemic
Agenda: The Facts! (Epidemiology/Risk Factors) Biological Classification/Phenotypes of Breast Cancer Treatment approach Local Systemic
Women lifetime risk of developing Breast Cancer? 1. 1/8 2. 1/25 3. 1/100 4. 1/500 5. 1/1000
New Cases / Deaths / 5-year Survival
% of new cases by Age Group
MKSAP: Which of the following is NOT a risk factor for Breast Cancer 1. Age older than 60 2. Caucasian 3. FH of Breast Cancer at age younger than 55 4. History of Tobacco Dependence 5. Age at time of 1 st live birth older than 30
What s my risk of developing of breast cancer? Age: 61 year old No prior personal history of breast cancer No personal or family history of BRCA mutations FH: 1 sister with breast cancer at age 56 No PMH or FH of BRCA mutations More than 10 years of tobacco dependence Menarche at age: 9 Age at time of 1 st live birth: 32 #1 Breast Biopsy in 2008 benign (no atypia) Race/Ethnicity: Caucasian
Risk of developing Breast Cancer YOUR PATIENT Average 61 yo 5-year risk 3.9 % 1.8% Lifetime risk (to age 90) 17.6% 8.8%
Chemoprevention in Breast Cancer
Risk Factors for Breast Cancer Relative Risk Sex (Female vs Male) 100 BRCA1 or BRCA2 mutations 6.0 14.0 FH: 1 st degree relative FH: 2 nd degree relative 1.4 13.6 1.5 1.8 Age ( 50 vs <50 yo) 6.5 Hx of Breast Atypical Hyperplasia Hx of Breast Hyperplasia Hx of Breast Biopsy 4.0 4.4 2.0 1.5 1.8 Nulliparity 2.0 Age at 1 st live birth (>30 vs <20) 1.3 2.2 Age at menopause ( 55 vs <55) 1.5 2.0 Age at menarche (<12 vs 14) 1.2 1.5 Hx of Hormone Replacement Therapy 1.0 1.5 Hx of Breast Radiation 1.4 Hx of Alcohol Consumption 1.1 4.0 Increased BMI Premenopausal Increased BMI - Postmenopausal 0.54 1.26 2.52
Who gets Breast Cancer? # of cases / 100,000
Who dies from Breast Cancer? # of cases / 100,000
BRCA-1 Associated Breast Cancer More common in Ashkenazi Jews Higher grade Tripe Negative (ER/PR negative HER-2 positive) Lifetime risk for individuals with BRCA 1 or BRCA 2 mutations 50% to 87% for invasive breast cancer 15% to 65% for invasive ovarian cancer * Prophylactic mastectomy is associated with 90% risk reduction of breast cancer
Agenda: The Facts! (Epidemiology/Risk Factors) Biological Classification/Phenotypes of Breast Cancer Treatment approach Local Systemic
Lobule DUCT
Myoepithelial Cell Epithelial Luminal Cell Basal Cell INVASIVE
Breast Cancer Non-Invasive: 15% DCIS 80% LCIS 20% Invasive Breast Cancer: 75% Ductal Invasive Breast Cancer 90% Lobular Invasive Breast Cancer 10% Other: 10% Phyllodes Tumor Pagets Disease Inflammatory Breast Cancer
LCIS Lobular Carcinoma in-situ
Lobular Carcinoma In Situ (LCIS) Noninvasive, usually incidental finding Optimal treatment is controversial (unknown) Often treated like DCIS Excision of lesion recommended NO need for LN evaluation
DCIS Ductal Carcinoma in-situ
DCIS Ductal Carcinoma In-Situ
Ductal Carcinoma In Situ (DCIS) Requires complete excision with negative margins Lumpectomy/Radiation therapy * Mastectomy NO need for LN evaluation Adjuvant Therapy? ER+: Hormonal therapy with the goal of reducing the risk in Ipsilateral/Contralateral breast cancer
NSABP-B24, JCO 2012 Tamoxifen vs Placebo in ER/PR positive DCIS Absolute Risk Reduction: Ipsilateral: 3.4% Contralateral: 3.2%
Invasive Breast Cancer
Invasive Breast Cancer 80-90% are Invasive Ductal Carcinoma 10% are Invasive Lobular Carcinoma (ER/PR positive) Local disease control: Removal of Tumor Mastectomy (Modified Radical Mastectomy) Lumpectomy + Radiation Therapy LN sampling via SN biopsy or axillary LN dissection
Triple Negative HER2 Positive ER/PR Positive Triple Positive HER2 Negative ER/PR Positive
Molecular Subtypes Triple Negative HER2+ Luminal B Luminal A % of Breast Cancers 15-20% 10-15% 20% 40% Receptor expression Triple Negative HER-2 Positive ER/PR POS HER2 POS ER/PR POS HER2 NEG Histological Grade HIGH (grade III) LOW (grade I) Prognosis Bad REALLY Bad Not to Bad Response to Medical Therapy Chemotherapy Trastuzumab Endocrine
Luminal A Luminal B Triple Negative HER-2 Positive
Luminal A Triple Negative Luminal B HER-2 Positive
Luminal A Triple Negative Luminal B HER-2 Positive
Triple Negative Breast Cancer
Triple Negative Breast Cancer (ER/PR Neg and Her2 Neg) Very aggressive Poor prognosis More common in young african-american women Most BRCA are Triple Negative (Basal like) Treatment: Only Chemotherapy
Risk of Recurrence ALL Others Triple Negative Dent, et al, Clinical Cancer Research 2007
HER-2 Positive Breast Cancer
Anti- HER2 therapy Monoclonal Antibodies Trastuzumab Pertuzumab Trastuzumab Emtansine (T-DM1) Tirosine Kinase Inhibitors Lapatinib
Chemo Alone vs Chemo+Trastuzumab NEJM 2001
Cleopatra Study Lancet 2013 Chemo+Trastuzumab vs Chemo+Trastuzumab+Pertuzumab
ER Positive Breast Cancer
Estrogen Levels in Women Ovarian Function NON-Ovarian
Estrogen Receptor Positive Breast Cancer Estrogen
Endocrine Therapy for ER+ Breast Cancer Selective Estrogen Receptor Modulators (SERMS) Tamoxifen Others In Pre and Post-Menopausal Women Aromatase Inhibitors Only In Post-Menopausal Women Anastrozole (Arimidex) Others Ovarian Suppression Only in Pre-Menopausal Women Surgical Oophorectomy Medical GnRH Agonists - Lupron
SERM (Tamoxifen)
Estrogen Levels in Women Ovarian Function NON-Ovarian
Estrogen Production after Menopause NON-Ovarian
Aromatase Inhibitors Steroidal (type 1) Nonsteroidal (type 2) 1 st Generation - Aminoglutethimide 2 nd Generation Formestane Fadrozole 3 rd Generation Exemestane (Aromasin) Anastrozole (Arimidex) Letrozole (Femara)
Tamoxifen or Aromatase Inhibitors in Postmenopausal Women? AI = Decreases Risk of Recurrence an extra 3% at 5 years J Clin Oncol. 2010 Jan 20;28(3):509-18. doi: 10.1200/JCO.2009.23.1274. Epub 2009 Nov 30. Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen.
Agenda: The Facts! (Epidemiology/Risk Factors) Biological Classification/Phenotypes of Breast Cancer Treatment approach Local Systemic
MKSAP #85 52 postmenopausal woman w/ recent dx of Breast Cancer Screening Mammogram: new 1.5 cm are of microcalcifications in the left breast without any associated mass No lymph nodes on exam FNA Infiltrating Ductal Carcinoma Grade 2 ER/PR Neg HER2 Neg
Next step in Management? 1) Lumpectomy + Axillary LN Dissection followed by XRT 2) Lumpectomy + Sentinel LN followed by XRT 3) Lumpectomy + Sentinel LN 4) Modified radical mastectomy 5) Modified radical mastectomy + XRT
Key POINTS in Management Mastectomy = Lumpectomy + XRT Equivalent disease control Never Lumpectomy Alone
EORTC 10801 trial Lancet 2012
MKSAP #54 52 yo female with breast lump FH: Breast Cancer Mother @85 FNA: Invasive Ductal Carcinoma Undergoes tumor resection + Sentinel LN Pathology: 1.2 cms Invasive Ductal Adenocarcinoma Negative Margins Sentinel LN Negative
Next step in management? 1) Full Axillary LN Dissection 2) Genetic testing for BRCA1/2 3) Tumor ER/PR/HER-2 assay 4) PET CT scan 5) Chemotherapy followed by radiation
MKSAP #68 72 female in ER with 3 weeks of Hip Pain Hx of Stage I breast cancer 7 years ago Lumpectomy + XRT 5 years of Tamoxifen Bone Scan: Uptake suggestive of mets Bone Bx: Recurrence Breast Cancer ER+, PR neg, HER2 neg
Most appropriate next step? 1) Anastrozole and Alendronate 2) Anastrozole and Zoledronic Acid 3) Single agent chemotherapy 4) Tamoxifen and Alendronate 5) Tamoxifen and Zoledronic Acid
Key POINTS in Management Tumors smaller than 0.5 cms (T1a) DO NOT NEED ANYTHING ELSE AFTER RESECTION No chemo/endocrine/her-2 therapy Tumors between 0.5-1 cms (T1b) depends on grade (unlikely to be tested) Low grade treat as T1a High grade treat as T1c Tumors larger than 1 cm (T1c) are associated with a risk of recurrence that exceeds 10% Therefore systemic therapy is warranted
Key POINTS in Management Most important prognostic indicator in Breast Cancer: Axillary LN Involvement
Systemic Treatment in Breast Cancer Local Disease LN Positive Metastatic Disease Triple Negative Chemotherapy Chemotherapy Chemotherapy HER-2 Positive Chemo + Anti-HER-2 Therapy Luminal A Endocrine Tx +/- Chemotherapy Chemotherapy + Endocrine Tx Endocrine Tx Luminal B Chemo + Anti-Her-2 Therapy +/- Endocrine Therapy
Thank You!