{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:35:39Z","timestamp":1760315739327,"version":"build-2065373602"},"reference-count":19,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T00:00:00Z","timestamp":1713312000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2024,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Several recurring pathogenic variants (PVs) in <jats:italic>BRCA1\/BRCA2<\/jats:italic> and additional cancer susceptibility genes are described in the ethnically diverse Israeli population. Since 2019, testing for these recurring PVs is reimbursed unselectively for all patients with breast cancer (BC) in Israel. The aim was to evaluate the yield of genotyping for these PVs in non\u2010Ashkenazi Jewish (AJ) patients with BC diagnosed \u2265age 50 years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical and genotyping data of all patients with BC undergoing oncogenetic counseling at the Oncology Institute at Sheba Medical Center from June 2017 to December 2023 were reviewed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 2706 patients with BC (mean age at diagnosis, 54 years; range, 20\u201392 years) counseled, 515 patients of non\u2010AJ (all four grandparents) descent, diagnosed \u2265age 50 years of age were genotyped, 55 with triple\u2010negative BC (TNBC) and 460 with non\u2010TNBC. One of the recurring PVs in <jats:italic>BRCA1\/BRCA2<\/jats:italic> were detected in 12.7% (7\/55) of TNBC patients and 0.65% (3\/460) of non\u2010TNBC. One patient with non\u2010TNBC had <jats:italic>PMS2<\/jats:italic> PV. Low\u2010penetrance variants were found in 2.5% of genotyped TNBC and in 3.7% of patients with non\u2010TNBC, including <jats:italic>CHEK2<\/jats:italic> c.499G&gt;A (<jats:italic>n<\/jats:italic>\u00a0=\u00a03), <jats:italic>APC<\/jats:italic> c.3920T\u00a0&gt;\u00a0A (<jats:italic>n<\/jats:italic>\u00a0=\u00a04), and heterozygous <jats:italic>MUTYH<\/jats:italic> c.1187G&gt;A (<jats:italic>n<\/jats:italic>\u00a0=\u00a05). Following first\u2010pass genotyping, 146 patients performed multigene panel testing, none carried a <jats:italic>BRCA1\/BRCA2<\/jats:italic> PV, and only 5\/127 non\u2010TNBC (3.9%) harbored PVs in <jats:italic>CHEK2<\/jats:italic> (<jats:italic>n<\/jats:italic>\u00a0=\u00a02, c.846+1G&gt;C and c.592+3A&gt;T), <jats:italic>ATM<\/jats:italic> c.103C&gt;T (<jats:italic>n<\/jats:italic>\u00a0=\u00a02), and <jats:italic>NBN<\/jats:italic> c.966C&gt;G (<jats:italic>n<\/jats:italic>\u00a0=\u00a01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The observed low rates of PV detection in non\u2010AJ non\u2010TNBC cases \u2265age 50 years at diagnosis, mostly for clinically insignificant variants, questions the justification of unselected genotyping in this subset of patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.35329","type":"journal-article","created":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T14:14:05Z","timestamp":1713363245000},"page":"2763-2769","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeted genotyping for recurring variants in cancer susceptibility genes in non\u2010Ashkenazi Jewish patients with breast cancer diagnosed \u226550 years"],"prefix":"10.1002","volume":"130","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4068-9514","authenticated-orcid":false,"given":"Rinat","family":"Bernstein\u2010Molho","sequence":"first","affiliation":[{"name":"The Suzanne Levy\u2010Gertner Oncogenetics Unit Sheba Tel Hashomer Medical Center  Ramat\u2010Gan Israel"},{"name":"Faculty of Medical and Health Sciences School of Medicine Tel\u2010Aviv University  Tel\u2010Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Narmeen Abu","family":"Shhada","sequence":"additional","affiliation":[{"name":"Breast cancer Institute The Jusidman Cancer Center Sheba Tel Hashomer Medical Center  Ramat\u2010Gan Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yael","family":"Laitman","sequence":"additional","affiliation":[{"name":"The Suzanne Levy\u2010Gertner Oncogenetics Unit Sheba Tel Hashomer Medical Center  Ramat\u2010Gan Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iris","family":"Netzer","sequence":"additional","affiliation":[{"name":"The Suzanne Levy\u2010Gertner Oncogenetics Unit Sheba Tel Hashomer Medical Center  Ramat\u2010Gan Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shelley","family":"Shoval","sequence":"additional","affiliation":[{"name":"The Suzanne Levy\u2010Gertner Oncogenetics Unit Sheba Tel Hashomer Medical Center  Ramat\u2010Gan 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