Evaluation & Management of PowerPoint Cover Title. the High Risk Population. High Risk Clinic

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Evaluation & Management of PowerPoint Cover Title the High Risk Population High Risk Clinic Subtitle Joanna Would Springman, Go Here PA-C

Assessment Genetics Known genetic mutation Family history with lifetime risk >20% High Risk Lesions Atypical Ductal Hyperplasia (ADH) Atypical Lobular Hyperplasia (ALH) Lobular Carcinoma In Situ (LCIS) Prior Mantle Irradiation for Hodgkin's Lymphoma 2

Case Study 44 y/o female with family history of BC in mother (dx at 47, contralateral at 69 with VUS PALB2). BMI 20, non smoker, 1 glass of wine/wk, avid exerciser Screening mammogram 8 months prior BIRADS 1 Presents for High Risk Evaluation TC score 31% MRI BIRADS 4 Biopsy invasive ductal carcinoma Surgery 1.2 cm, Stage I, ER positive breast cancer 3

Tyrer-Cuzick http://www.cancertechnology.co.uk/ibis-software-tyrer-cuzick-model 4

Gail Model https://www.cancer.gov/bcrisktool/ 5

6 Risk Factors

7 Risk Factors

Radiation Exposure Ages 10-30 Median relative risk of 5.2 Average latency period of 14 years 8

Atypical Hyperplasia Some neoplastic characteristics of DCIS Median relative risk of 5.3 + positive family history = median relative risk of 11 Risk of breast cancer 30-40% within 5 years diagnosis 9

Lobular Carcinoma In Situ High risk lesion, not preinvasive Median relative risk of 16.4 Risk of breast cancer 7-36% 10

Action Family History/Irradiation Clinical exam every 6-12 months Recommend annual MRI (>25 years) Recommend annual mammogram (>30 years) Genetic counseling High Risk Lesions Clinical exam every 6-12 months Recommend annual mammogram (>30 years) Both Risk reduction strategies Breast awareness 11

Risk Reducing Agents Tamoxifen Reduces risk of breast cancer by 49% Atypical Hyperplasia reduces risk by 86% SSRI interaction Annual GYN exam with intact uterus Raloxifene (Evista) Post-menopausal females only Short term similar to tamoxifen Aromatase Inhibitor not FDA approved Exemestane 25mg reduces risk by 65% Anastrozole 1mg reduces risk by 53% 12

Choosing Among Anti-Depressants Effect on CYP2D6 Minimal Mild Moderate Strong Drug venlafaxine desvenlafaxine mirtazapine citalopram escitalopram nefazodone duloxetine sertraline fluvoxamine paroxetine fluoxetine bupropion 13

Risk Reducing Surgery Those with specific genetic mutations only per NCCN guidelines BRCA1 BRCA2 CDH1 PTEN TP52 PALB2 ATM 14

Things we still don t know How long to continue screening MRIs When to reevaluate a patient as high risk 15

Case Study 68 y/o female with family history significant for breast cancer in daughter (46 BRCA2 positive), mom (83), PAunt (50), Paunt (70), PCousin, MAunt, ovarian cancer in Pcousin, colon cancer in brother (59), prostate cancer in brother (50) and father (60) BSM 5 months earlier BIRADS 1 Referral to Genetic Counselor Genetic testing done negative for any mutations TC 20.9% High Risk Evaluation MRI BIRADS 4 Biopsy = papillary lesion Surgery 2.1cm DCIS, Stage 0, ER positive 16

References http://www.breastcancer.org/research-news/20140307 http://www.cancertechnology.co.uk/ibis-software-tyrer-cuzick-model https://www.cancer.gov/bcrisktool/ https://www.ncbi.nlm.nih.gov/pmc/articles/pmc1514477/ National Comprehensive Cancer Network. Breast Cancer Screening and Diagnosis (Version 1.2016). https://www.nccn.org/professionals/physician_gls/pdf/breast-screening.pdf. Accessed March 28, 3017. https://www.ncbi.nlm.nih.gov/pubmed/19196674 https://www.ncbi.nlm.nih.gov/pubmed/20439627 Fisher B. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 1998;90(18):1371-1388. National Comprehensive Cancer Network. Breast Cancer Risk Reduction (Version 1.2017). https://www.nccn.org/professionals/physician_gls/pdf/breast_risk.pdf. Accessed March 28, 3017. http://www.health.harvard.edu/newsletter_article/antidepressants-and-tamoxifen National Comprehensive Cancer Network. Genetic/Familial High-Risk Assessment: Breast and Ovarian (Version 2.2017). https://www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf. Accessed March 28, 3017. 17