Hereditary Breast and Ovarian Cancer Risk Management
Hank Schmidt MD PhD Associate Professor of Surgery Icahn School of Medicine at Mount Sinai Dubin Breast Center of the Tisch Cancer Institute Risk Management of HBOC
To identify strategies to reduce risk of future cancer due to hereditary breast and ovarian cancer.
To describe surveillance strategies related to Learning hereditary breast and ovarian cancer. Objectives
To describe treatment approaches among cancer patients with a BRCA1/2 genetic alterations. Hank Schmidt, MD PhD Bio
• Surgical oncologist specializing in care of patients with breast cancer and those at increased risk for breast cancer at the Dubin Breast Center of the Tisch Cancer Institute, Mount Sinai Health System
• Associate Professor of Surgery at the Icahn School of Medicine at Mount Sinai
• Research on how to better define patients who will truly benefit from breast surgery and reducing unnecessary treatment. Review: Breast Cancer
Out of 100 women with breast cancer, 5 to 10 can be explained by genetic alterations Review: Second Breast Cancers
Out of 100 Out of 100 women women with with breast cancer breast cancer who have a without BRCA1 or BRCA2 BRCA1 or gene alteration, up BRCA2, 7 will to 60 will get a get a second second breast breast cancer cancer within 25 within 25 years after years after diagnosis. diagnosis. Review: Future Ovarian Cancer Risk
Out of 100 Out of 100 women with a women BRCA1 or without BRCA2 gene BRCA1 or alteration, BRCA2, up to 40 will get will get 1 ovarian cancer ovarian by the time cancer by they are 70 the time years old. they are 70 years old. Comprehensive Cancer Center High Risk Program
• Prospective care to define risk and appropriate evidence based risk management strategies • Screening for other cancers and early diagnosis • Prophylactic surgery (removal of ovaries or breasts) and follow up care • Coordination of care among multiple providers and disease management teams • Genetic testing of family members • Education and Research Risk Management Strategies
CBE = Clinical breast exam
MRI = Magnetic Resonance Imaging; creates detailed images Breast Cancer Risk Management Strategies for Women with BRCA1/2 • Screening for early detection: • MRI • Mammogram
• Medications • Chemoprevention
• Surgery • Bilateral total mastectomy • Nipple sparing mastectomy
Slide adapted; courtesy of Beth Peshkin, CGC
NCCN Guidelines, HBOC v1. 2018 High Intensity Screening Imaging
Annual Screening Mammogram • Begin age 30 for BRCA mutation carriers • Numerous studies demonstrate clear survival benefit • 3D Tomosynthesis
High Intensity Screening Imaging
•Annual MRI •Most sensitive means of cancer detection •False positive rate is the trade off •No utility for Ultrasound Medications to Reduce Risk Chemoprevention • Tamoxifen – NSABP-P1 Trial (1998) - 5 years: ↓ invasive breast cancer risk 49% - Side effects: endometrial cancer, blood clots
• Raloxifene (postmenopausal) • 76% as effective as Tamoxifen with lower side effects
• Aromatase inhibitors (postmenopausal) • No increased risk of blood clots
Surgery: Risk Reducing Mastectomy
• Prophylactic (preventive) Mastectomy
• Contralateral mastectomy (1 breast) • For women who have had 1 breast removed for treatment of breast cancer • Does not improve survival rates • Cosmesis (attention to how the breast looks after surgery)
Reducing Risk of Breast Cancer: Surgery Reynolds 2011 Nipple Sparing Mastectomy
• Importance of Patient Selection – Anatomy
• Staged Procedure • Possible reduction surgery • Nipple Delay procedure • Definitive subcutaneous mastectomy Ovarian Cancer Risk Management Strategies for Women with BRCA1/2
• Most ovarian cancers are not detected early
• There are NO reliable screening tests for ovarian cancer
• Removal of ovaries and fallopian tubes is recommended after childbearing by age 35-40
• Total hysterectomy may be recommended for BRCA1 carriers
Slide adapted; courtesy of Beth Peshkin, CGC NCCN Guidelines, HBOC v1. 2018 Surgical Options for Ovarian Cancer Risk Reductions
• Risk Reducing Oophorectomy (bilateral prophylatic salpingo-oophorectomy) • Removal of the ovaries and fallopian tubes • ↓ risk by removing estrogen • Ovarian cancer risk ↓ by 80% • Breast cancer risk ↓ by 50%
• After childbearing is complete: • BRCA1 – recommended ages 35-40 • BRCA2 – recommended ages 40-45
Men with BRCA1/2
• Multiple Cancers • Male Breast Cancer 1.2% (BRCA1) and 6.8% (BRCA2) • Pancreas, Gastric, Colorectal, Gallbladder, Bile duct
• Prostate cancer • Up to 30-40% risk in BRCA2 • Possibly earlier onset • Aggressive and lethal • May shift risks/benefits for prostate cancer screening (with PSA blood tests), biopsy, and treatment Slide adapted; courtesy of Beth Peshkin, CGC NCCN Guidelines, HBOC v1. 2018 Bancroft EK, et al. Eur Urol 2014;66:489 Gleicher S, et al. Prostate 2016;76:1135 Summary
• For women with BRCA1/2 gene mutations
• Bilateral prophylatic salpingo-oophorectomy by age 35-40
• Breast screening: MRI at 25yo, MRI + mmg at 30yo • Prophylactic BSO by 40yo and surveillance imaging should offer similar survival to Bilateral mastectomy
Thank you
Questions or comments:
Chemoprevention in BRCA carriers: Research Studies
• King 2000 : Reviewed BRCA patients in the NSABP-P1 Trial • 62% reduction in risk of breast cancer in BRCA2 carriers
• Narod 2006: Approx 50% reduction in risk for both BRCA1 and BRCA2 carriers (5 yrs of Tamoxifen)
• Shafaee 2015: Aromatase Inhibitors reduce risk in BRCA1&2 • Prospective clinical trial of AI + OS for prevention in BRCA (CIBRAC)