Dataset Information

Clinical outcome of breast cancer in carriers of BRCA1 and BRCA2 mutations according to molecular subtypes.

ABSTRACT: BRCA1/BRCA2 genes play a central role in DNA repair and their mutations increase sensitivity to DNA-damaging agents. There are conflicting data regarding the prognostic value of BRCA germline mutations in breast cancer (BC) patients. We collected clinical, pathological and genetic data of a cohort 925 BC patients preselected for genetic screening and treated with neoadjuvant or adjuvant chemotherapy, of whom 266 were BRCA carriers. Overall, 171 women carried a BRCA1 mutation, 95 carried a BRCA2 mutation, and 659 were non-carriers. In the entire cohort, there was a prolonged disease-free survival (DFS) for BRCA carriers (hazard ratio (HR)?=?0.63; 95% confidence interval (CI), 0.44-0.90 for BRCA1; HR?=?0.72; 95%CI, 0.47-1.1 for BRCA2; p?=?0.020) and a trend toward prolonged disease-specific survival (DSS; HR?=?0.65; 95%CI, 0.40-1.1 for BRCA1; HR?=?0.78; 95%CI, 0.44-1.38 for BRCA2; p?=?0.19) though not statistically significant. In the TNBC group, BRCA carriers had prolonged DFS (adjusted HR?=?0.50; 95%CI, 0.28-0.89 for BRCA1; adjusted HR?=?0.37; 95%CI, 0.11-1.25, for BRCA2; p?=?0.034) and DSS (adjusted HR?=?0.42; 95%CI, 0.21-0.82 for BRCA1; adjusted HR?=?0.45; 95%CI, 0.11-1.9 for BRCA2; p?=?0.023). In the non-TNBC group, the BRCA1 or BRCA2 mutations did not have any impact on survival. These results suggest that BRCA1/BRCA2 germline mutations are associated with prolonged survival only if women were diagnosed with TNBC.

SUBMITTER: De Talhouet S

PROVIDER: S-EPMC7184602 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Clinical outcome of breast cancer in carriers of BRCA1 and BRCA2 mutations according to molecular subtypes.

De Talhouet Solene S Peron Julien J Vuilleumier Aurelie A Friedlaender Alex A Viassolo Valeria V Ayme Aurélie A Bodmer Alexandre A Treilleux Isabelle I Lang Noemie N Tille Jean- Christophe JC Chappuis Pierre O PO Buisson Adrien A Giraud Sophie S Lasset Christine C Bonadona Valerie V Trédan Olivier O Labidi-Galy S Intidhar SI

Scientific reports 20200427 1

BRCA1/BRCA2 genes play a central role in DNA repair and their mutations increase sensitivity to DNA-damaging agents. There are conflicting data regarding the prognostic value of BRCA germline mutations in breast cancer (BC) patients. We collected clinical, pathological and genetic data of a cohort 925 BC patients preselected for genetic screening and treated with neoadjuvant or adjuvant chemotherapy, of whom 266 were BRCA carriers. Overall, 171 women carried a BRCA1 mutation, 95 carried a BRCA2 ...[more]

PMID: 32341426

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Project description:Pathogenic germline mutations in BRCA1 or BRCA2 are detected in less than one third of families with a strong history of breast cancer. It is therefore expected that mutations still remain undetected by currently used screening methods. In addition, a growing number of BRCA1/2 sequence variants of unclear pathogen significance are found in the families, constituting an increasing clinical challenge. New methods are therefore needed to improve the detection rate and aid the interpretation of the clinically uncertain variants. In this study we analyzed a series of 33 BRCA1, 22 BRCA2, and 128 sporadic tumors by RNA profiling to investigate the classification potential of RNA profiles to predict BRCA1/2 mutation status. We found that breast tumors from BRCA1 and BRCA2 mutation carriers display characteristic RNA expression patterns, allowing them to be distinguished from sporadic tumors. The majority of BRCA1 tumors were basal-like while BRCA2 tumors were mainly luminal B. Using RNA profiles, we were able to distinguish BRCA1 tumors from sporadic tumors among basal-like tumors with 83% accuracy and BRCA2 from sporadic tumors among luminal B tumors with 89% accuracy. Furthermore, subtype-specific BRCA1/2 gene signatures were successfully validated in two independent data sets with high accuracies. Although additional validation studies are required, indication of BRCA1/2 involvement (“BRCAness”) by RNA profiling could potentially be valuable as a tool for distinguishing pathogenic mutations from benign variants, for identification of undetected mutation carriers, and for selecting patients sensitive to new therapeutics such as PARP inhibitors. Gene expression profiling of 183 breast tumor samples. Breast tumors from hereditary breast cancer patients carrying a pathogenic BRCA1 (n=33) or BRCA2 (n=22) germ-line mutation were included in the study. Serving as a representative control group, primary breast tumor samples (n=128) were randomly selected. The study was conducted using Agilent-029949 Custom SurePrint G3 Human GE 8x60K Microarray platform. For cross-platform validation, a subset of the tumor samples (92 of the 183 samples) were analyzed by our in-house spotted microarray platform.

Dataset Information

Clinical outcome of breast cancer in carriers of BRCA1 and BRCA2 mutations according to molecular subtypes.

Publications

Clinical outcome of breast cancer in carriers of BRCA1 and BRCA2 mutations according to molecular subtypes.

Similar Datasets

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