Breast Cancer. Dr. Andres Wiernik 2017
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1 Breast Cancer Dr. Andres Wiernik 2017
2
3 Agenda: The Facts! (Epidemiology/Risk Factors) Biological Classification/Phenotypes of Breast Cancer Treatment approach Local Systemic
4 Agenda: The Facts! (Epidemiology/Risk Factors) Biological Classification/Phenotypes of Breast Cancer Treatment approach Local Systemic
5 Women lifetime risk of developing Breast Cancer? 1. 1/8 2. 1/ / / /1000
6
7 New Cases / Deaths / 5-year Survival
8 % of new cases by Age Group
9
10 MKSAP: Which of the following is NOT a risk factor for Breast Cancer 1. Age older than Caucasian 3. FH of Breast Cancer at age younger than History of Tobacco Dependence 5. Age at time of 1 st live birth older than 30
11 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
12
13 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%
14 Chemoprevention in Breast Cancer
15
16 Risk Factors for Breast Cancer Relative Risk Sex (Female vs Male) 100 BRCA1 or BRCA2 mutations FH: 1 st degree relative FH: 2 nd degree relative Age ( 50 vs <50 yo) 6.5 Hx of Breast Atypical Hyperplasia Hx of Breast Hyperplasia Hx of Breast Biopsy Nulliparity 2.0 Age at 1 st live birth (>30 vs <20) Age at menopause ( 55 vs <55) Age at menarche (<12 vs 14) Hx of Hormone Replacement Therapy Hx of Breast Radiation 1.4 Hx of Alcohol Consumption Increased BMI Premenopausal Increased BMI - Postmenopausal
17 Who gets Breast Cancer? # of cases / 100,000
18 Who dies from Breast Cancer? # of cases / 100,000
19 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
20 Agenda: The Facts! (Epidemiology/Risk Factors) Biological Classification/Phenotypes of Breast Cancer Treatment approach Local Systemic
21
22 Lobule DUCT
23 Myoepithelial Cell Epithelial Luminal Cell Basal Cell INVASIVE
24 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
25 LCIS Lobular Carcinoma in-situ
26 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
27 DCIS Ductal Carcinoma in-situ
28 DCIS Ductal Carcinoma In-Situ
29 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
30 NSABP-B24, JCO 2012 Tamoxifen vs Placebo in ER/PR positive DCIS Absolute Risk Reduction: Ipsilateral: 3.4% Contralateral: 3.2%
31 Invasive Breast Cancer
32 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
33 Triple Negative HER2 Positive ER/PR Positive Triple Positive HER2 Negative ER/PR Positive
34 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
35 Luminal A Luminal B Triple Negative HER-2 Positive
36 Luminal A Triple Negative Luminal B HER-2 Positive
37 Luminal A Triple Negative Luminal B HER-2 Positive
38 Triple Negative Breast Cancer
39 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
40 Risk of Recurrence ALL Others Triple Negative Dent, et al, Clinical Cancer Research 2007
41 HER-2 Positive Breast Cancer
42
43 Anti- HER2 therapy Monoclonal Antibodies Trastuzumab Pertuzumab Trastuzumab Emtansine (T-DM1) Tirosine Kinase Inhibitors Lapatinib
44
45 Chemo Alone vs Chemo+Trastuzumab NEJM 2001
46
47 Cleopatra Study Lancet 2013 Chemo+Trastuzumab vs Chemo+Trastuzumab+Pertuzumab
48 ER Positive Breast Cancer
49 Estrogen Levels in Women Ovarian Function NON-Ovarian
50 Estrogen Receptor Positive Breast Cancer Estrogen
51 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
52 SERM (Tamoxifen)
53 Estrogen Levels in Women Ovarian Function NON-Ovarian
54 Estrogen Production after Menopause NON-Ovarian
55 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)
56 Tamoxifen or Aromatase Inhibitors in Postmenopausal Women? AI = Decreases Risk of Recurrence an extra 3% at 5 years J Clin Oncol Jan 20;28(3): doi: /JCO Epub 2009 Nov 30. Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen.
57
58 Agenda: The Facts! (Epidemiology/Risk Factors) Biological Classification/Phenotypes of Breast Cancer Treatment approach Local Systemic
59 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
60 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
61 Key POINTS in Management Mastectomy = Lumpectomy + XRT Equivalent disease control Never Lumpectomy Alone
62 EORTC trial Lancet 2012
63 MKSAP #54 52 yo female with breast lump FH: Breast Cancer FNA: Invasive Ductal Carcinoma Undergoes tumor resection + Sentinel LN Pathology: 1.2 cms Invasive Ductal Adenocarcinoma Negative Margins Sentinel LN Negative
64 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
65 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
66 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
67 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 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
68 Key POINTS in Management Most important prognostic indicator in Breast Cancer: Axillary LN Involvement
69 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
70 Thank You!
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