Next Generation Sequencing-Based Genetic Screening In Breast Cancer Risk For Relatives Of Brca Positive Index Cases - A Subcontinent Experience

Based on existing literature, BRCA gene mutations are present in over 10% of all breast cancers. Since germ line BRCA mutations are inherited in an autosomal dominant fashion, the identification of a positive genetic mutation in an index case, warrants screening of at-risk relatives. The importance of genetic screening lies in that with a positive test result, strategies of risk reduction -which not only limits to prophylactic mastectomies and bilateral salphingo-oophorectomies, but also to adaptation of favorable life style changes and early screening in at risk relatives. We report our outcomes of genetic screening in breast cancers. This study was conducted between the year 2017 to 2019.All breast cancer patients who had clinical indication for genetic screening, based on the existing malignancy and family history criteria were advised the same after a genetic counselling. Germline mutation in BRCA1 and BRCA 2 were tested and evaluated using next generation sequencing platform for and on identification of the same, patients and relatives were counseled regarding the need for genetic screening in at risk relatives and if willing underwent the same. Among the 469 breast cancer patients who were screened for BRCA mutation based on existing clinical indications for genetic screening, 131 (27.9%) patients were identified with BRCA positivity. Based on the index case positivity, screening of at-risk relative was advised. 18 index mutation positive cases had two each of their first-degree relatives screened and 80 patients had one relative screened. 98 out of 131(74.8%) had at-least one relative screened and 33 of 131 (25.2%) were not willing for screening of at-risk relatives due to economic and social barriers. The BRCA positivity rate among screened at-risk relative was 37%. From our observation, the rates of BRCA positivity among breast cancer patients with clinical indication for genetic screening in our series is higher than that reported in literature. By virtue of health care policies that cover genetic screening of BRCA mutations of index patient and at-risk first-degree relatives and by effectively tackling with the pretest anxiety of a positive test result, the yield of BRCA screening can be improved and effective risk reduction approaches can be implemented.Abstract 3175; TableINDEX CASES SCREENEDAT RISK RELATIVES SCREENEDTOTAL NUMBER469116BRCA 1 POSITIVE87(18.5%)25(21.5%)BRCA 2 POSITIVE42(8.9%)18(15.5%)BRCA 1 & BRCA 2 POSITIVE2(0.4%)- Open table in a new tab