Incidence and Outcome of BRCA Mutations in Unselected Patients with Triple Receptor-Negative Breast Cancer.

Hdl Handle:
http://hdl.handle.net/10147/126080
Title:
Incidence and Outcome of BRCA Mutations in Unselected Patients with Triple Receptor-Negative Breast Cancer.
Authors:
Gonzalez-Angulo, Ana M; Timms, 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.
Citation:
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 Research
Issue Date:
1-Mar-2011
URI:
http://hdl.handle.net/10147/126080
DOI:
10.1158/1078-0432.CCR-10-2560
PubMed ID:
21233401
Abstract:
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.
Item Type:
Article
Language:
en
ISSN:
1078-0432

Full metadata record

DC FieldValue Language
dc.contributor.authorGonzalez-Angulo, Ana Men
dc.contributor.authorTimms, Kirsten Men
dc.contributor.authorLiu, Shuyingen
dc.contributor.authorChen, Huiqinen
dc.contributor.authorLitton, Jennifer Ken
dc.contributor.authorPotter, Jenniferen
dc.contributor.authorLanchbury, Jerry Sen
dc.contributor.authorStemke-Hale, Katherineen
dc.contributor.authorHennessy, Bryan Ten
dc.contributor.authorArun, Banu Ken
dc.contributor.authorHortobagyi, Gabriel Nen
dc.contributor.authorDo, Kim-Anhen
dc.contributor.authorMills, Gordon Ben
dc.contributor.authorMeric-Bernstam, Fundaen
dc.date.accessioned2011-03-29T14:00:17Z-
dc.date.available2011-03-29T14:00:17Z-
dc.date.issued2011-03-01-
dc.identifier.citationIncidence and Outcome of BRCA Mutations in Unselected Patients with Triple Receptor-Negative Breast Cancer. 2011, 17 (5):1082-9 Clin. Cancer Res.en
dc.identifier.issn1078-0432-
dc.identifier.pmid21233401-
dc.identifier.doi10.1158/1078-0432.CCR-10-2560-
dc.identifier.urihttp://hdl.handle.net/10147/126080-
dc.description.abstractTo 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.-
dc.description.abstractMedian 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.-
dc.description.abstractIn 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.-
dc.language.isoenen
dc.titleIncidence and Outcome of BRCA Mutations in Unselected Patients with Triple Receptor-Negative Breast Cancer.en
dc.typeArticleen
dc.contributor.departmentAuthors' 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.en
dc.identifier.journalClinical cancer research : an official journal of the American Association for Cancer Researchen
dc.description.provinceLeinster-

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