Incidence and Outcome of BRCA Mutations in Unselected Patients with Triple Receptor-Negative Breast Cancer.
Authors
Gonzalez-Angulo, Ana MTimms, Kirsten M
Liu, Shuying
Chen, Huiqin
Litton, Jennifer K
Potter, Jennifer
Lanchbury, Jerry S
Stemke-Hale, Katherine
Hennessy, Bryan T
Arun, Banu K
Hortobagyi, Gabriel N
Do, Kim-Anh
Mills, Gordon B
Meric-Bernstam, Funda
Affiliation
Authors' Affiliations: Departments of Breast Medical Oncology, Systems Biology, Biostatistics, and Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas; Myriad Genetics Inc., Salt Lake City, Utah; and Department of Medical Oncology, Beaumont Hospital, Dublin, Ireland.Issue Date
2011-03-01
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Incidence and Outcome of BRCA Mutations in Unselected Patients with Triple Receptor-Negative Breast Cancer. 2011, 17 (5):1082-9 Clin. Cancer Res.Journal
Clinical cancer research : an official journal of the American Association for Cancer ResearchDOI
10.1158/1078-0432.CCR-10-2560PubMed ID
21233401Abstract
To investigate the incidence of germline and somatic BRCA1/2 mutations in unselected patients with triple-negative breast cancer (TNBC) and determine the prognostic significance of carrying a mutation. Methods: DNA was obtained from 77 TNBC and normal tissues. BRCA1/2 exons/flanking regions were sequenced from tumor and patients classified as mutant or wild type (WT). Sequencing was repeated from normal tissue to identify germline and somatic mutations. Patient characteristics were compared with chi-square. Survival was estimated by Kaplan-Meier method and compared with log-rank. Cox proportional hazards models were fit to determine the independent association of mutation status with outcome.Median age was 51 years (27-83 years). Fifteen patients (19.5%) had BRCA mutations: 12 (15.6%) in BRCA1 (one somatic), and 3 (3.9%) in BRCA2. Patients with BRCA mutations tended to be younger than WT, (P = 0.005). Grade, histology, and stage were not associated with mutation status. At a median follow-up of 43 months (7-214 months), there were 33 (42.9%) recurrences and 35 (45.5%) deaths. Five-year recurrence-free survival estimates were 51.7% for WT versus 86.2% for patients with mutations, (P = 0.031); and 5-year overall survival estimates were 52.8% for WT versus 73.3% for patients with mutations (P = 0.225). After adjustment, patients with BRCA mutations had a significantly better RFS (HR: 0.19, 95% CI: 0.045-0.79, P = 0.016) compared with WT.
In this unselected cohort of TNBC, we found a 19.5% incidence of BRCA mutations. Genetic testing should be discussed with patients with TNBC. Patients with TNBC with BRCA mutations had a significantly lower risk of relapse. Clin Cancer Res; 17(5); 1082-9. ©2011 AACR.
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ArticleLanguage
enISSN
1078-0432ae974a485f413a2113503eed53cd6c53
10.1158/1078-0432.CCR-10-2560
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