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Publication Detail

Title: Mutation Rates in Cancer Susceptibility Genes in Patients With Breast Cancer With Multiple Primary Cancers.

Authors: Maxwell, Kara N; Wenz, Brandon M; Kulkarni, Abha; Wubbenhorst, Bradley; D'Andrea, Kurt; Weathers, Benita; Goodman, Noah; Vijai, Joseph; Lilyquist, Jenna; Hart, Steven N; Slavin, Thomas P; Schrader, Kasmintan A; Ravichandran, Vignesh; Thomas, Tinu; Hu, Chunling; Robson, Mark E; Peterlongo, Paolo; Bonanni, Bernardo; Ford, James M; Garber, Judy E; Neuhausen, Susan L; Shah, Payal D; Bradbury, Angela R; DeMichele, Angela M; Offit, Kenneth; Weitzel, Jeffrey N; Couch, Fergus J; Domchek, Susan M; Nathanson, Katherine L

Published In JCO Precis Oncol, (2020)

Abstract: PURPOSE: Women with breast cancer have a 4%-16% lifetime risk of a second primary cancer. Whether mutations in genes other than BRCA1/2 are enriched in patients with breast and another primary cancer over those with a single breast cancer (S-BC) is unknown. PATIENTS AND METHODS: We identified pathogenic germline mutations in 17 cancer susceptibility genes in patients with BRCA1/2-negative breast cancer in 2 different cohorts: cohort 1, high-risk breast cancer program (multiple primary breast cancer [MP-BC], n = 551; S-BC, n = 449) and cohort 2, familial breast cancer research study (MP-BC, n = 340; S-BC, n = 1,464). Mutation rates in these 2 cohorts were compared with a control data set (Exome Aggregation Consortium [ExAC]). RESULTS: Overall, pathogenic mutation rates for autosomal, dominantly inherited genes were higher in patients with MP-BC versus S-BC in both cohorts (8.5% v 4.9% [P = .02] and 7.1% v 4.2% [P = .03]). There were differences in individual gene mutation rates between cohorts. In both cohorts, younger age at first breast cancer was associated with higher mutation rates; the age of non-breast cancers was unrelated to mutation rate. TP53 and MSH6 mutations were significantly enriched in patients with MP-BC but not S-BC, whereas ATM and PALB2 mutations were significantly enriched in both groups compared with ExAC. CONCLUSION: Mutation rates are at least 7% in all patients with BRCA1/2 mutation-negative MP-BC, regardless of age at diagnosis of breast cancer, with mutation rates up to 25% in patients with a first breast cancer diagnosed at age < 30 years. Our results suggest that all patients with breast cancer with a second primary cancer, regardless of age of onset, should undergo multigene panel testing.

PubMed ID: 32954205 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

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