LAUSR

Background: Women with germline BRCA (gBRCA) mutations in the United States are typically diagnosed at the time of cancer diagnosis and most often undergo bilateral mastectomy. Israel9s population of 8 million includes over 3 million Jews of Ashkenazi ancestry, of whom 2.5% would be expected to have gBRCA based on population studies. Cross-ancestral and -racial marriages in Israel continue to expand the population at risk for gBRCA mutations. Gene typing for any woman in Israel can be obtained without cost through either the national health care system or genetic screening studies. The Noga Clinic (NC) in Jerusalem was started in September 2007 for women with documented gBRCA mutations at risk for breast and/or ovarian cancer to counsel them on risk-reducing (rr) surgical interventions and provide rigorous screening to diagnose cancer at its earliest stages. Screening is performed in compliance with NCCN and international recommendations. This report presents information from that unique population and clinical experience. Methods: Clinical records of women with at least one screening visit at NC through December 2015 were retrospectively reviewed. Women with a documented gBRCA mutation with or without a clinical history of breast/ovarian cancer were eligible for assessment every (q) 6 months (m): bilateral breast exam by an experienced breast surgeon (q6m), serum CA-125 (q6m), trans-vaginal ultrasound (q6m), bilateral mammography (q12m) and bilateral breast ultrasound (q12m) alternating with bilateral contrast enhanced MRI (q12m) beginning at age 25. Women are offered rr bilateral mastectomy (BMast); rr salpingo-oophorectomy is recommended by the age of 40. Cancer diagnoses and rr surgeries were recorded. Results: 611 women have undergone at least one screening assessment at the NC, of whom 44 had a prior cancer diagnosis. Age at the time of initial gene testing ranged from 20-87y (median 38). Of those with recorded mutation data, 272 women (57%) had mutations in gBRCA1, 205 (43%) in BRCA2, and 1 in both. Mutation specifics will be presented in detail. For the 567 women without a prior cancer diagnosis, median age at first screening visit was 37y (range 21-87) and total follow up was 2,141 person-years (per person range 1-9y, median 3.3). Only 21 women (4%) elected rrBMast at a median age of 42y (range 26-60); none developed breast cancer. In the remaining individuals, 31 breast cancers were diagnosed (58% gBRCA1, 42% gBRCA2) from the initiation of screening at a median age of 51y (range 28-88); the majority were DCIS and diagnosed at a median screening follow up of 2.8y. No participant was treated with anti-endocrine chemoprevention. There have been no breast cancer deaths. 5 women were diagnosed with ovarian cancer (all gBRCA1) of whom 1 died of the disease. Methods of cancer detection will be presented. Conclusion: This is the largest reported data set of women with gBRCA mutations without a prior breast or ovarian cancer diagnosis screened and followed over time. In this highly selected predominantly Jewish population in Israel, the great majority of women chose not to undergo rrBMast and have excellent outcomes when participating in regular and rigorous screening. Further follow-up is ongoing. Citation Format: Mor P, Levy-Lahad E, Beler U, Carmon M, Strano S, Hadar T, Olsha O, Rabinowitz R, Srebnik N, Simon E, Duchin R, Jackson M, Rabinovitch R. Screening, management, cancer diagnoses, and outcomes of women with germline BRCA mutations in Israel: The Noga Clinic experience [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-08-06.