Dataset Information

Outcome of ovarian cancer after breast cancer in BRCA1 and BRCA2 mutation carriers.

ABSTRACT:

Background

It is unknown whether a history of breast cancer (BC) affects the outcome of BRCA1/2-associated epithelial ovarian cancer (EOC). This was investigated in the current analysis.

Methods

We included 386 BRCA1/2-associated EOC patients diagnosed between 1980 and 2015. Progression-free survival (PFS), progression-free interval (PFI), overall survival (OS) and ovarian cancer-specific survival (OCSS) were compared between EOC patients with and without previous BC.

Results

BRCA-associated EOC patients with, vs without, a BC history had a significantly worse PFS and PFI (multivariate hazard ratio (HR_mult) 1.47; 95% confidence interval (CI) 1.03-2.08 and HR_mult 1.43; 95% CI 1.01-2.03), and a non-significantly worse OS (HR_mult 1.15; 95% CI 0.84-1.57) and OCSS (HR_mult 1.18; 95% CI 0.85-1.62). Ovarian cancer-specific survival was significantly worse for the subgroup treated with adjuvant chemotherapy for BC (HR_mult 1.99; 95% CI 1.21-3.31).

Conclusions

Our results suggest that BRCA1/2-associated EOC patients with a previous BC have a worse outcome than EOC patients without BC, especially when treated with adjuvant chemotherapy.

SUBMITTER: Zaaijer LH

PROVIDER: S-EPMC5104898 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Outcome of ovarian cancer after breast cancer in BRCA1 and BRCA2 mutation carriers.

Zaaijer Leendert H LH van Doorn Helena C HC Mourits Marian J E MJ van Beurden Marc M de Hullu Joanne A JA Adank Muriel A MA van Lonkhuijzen Luc R C W LR Vasen Hans F A HF Slangen Brigitte F M BF Gaarenstroom Katja N KN Zweemer Ronald P RP Vencken Peggy M L H PM Seynaeve Caroline C Kriege Mieke M

British journal of cancer 20161018 10

<h4>Background</h4>It is unknown whether a history of breast cancer (BC) affects the outcome of BRCA1/2-associated epithelial ovarian cancer (EOC). This was investigated in the current analysis.<h4>Methods</h4>We included 386 BRCA1/2-associated EOC patients diagnosed between 1980 and 2015. Progression-free survival (PFS), progression-free interval (PFI), overall survival (OS) and ovarian cancer-specific survival (OCSS) were compared between EOC patients with and without previous BC.<h4>Results</ ...[more]

PMID: 27755534

Similar Datasets

Project description:BackgroundGenome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates.MethodsWe constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS.ResultsThe PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2×10 -53 ). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2×10 -20 ). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS.ConclusionsBC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management.

Project description:BACKGROUND: Increased number of single nucleotide substitutions is seen in breast and ovarian cancer genomes carrying disease-associated mutations in BRCA1 or BRCA2. The significance of these genome-wide mutations is unknown. We hypothesize genome-wide mutation burden mirrors deficiencies in DNA repair and is associated with treatment outcome in ovarian cancer. METHODS AND RESULTS: The total number of synonymous and non-synonymous exome mutations (Nmut), and the presence of germline or somatic mutation in BRCA1 or BRCA2 (mBRCA) were extracted from whole-exome sequences of high-grade serous ovarian cancers from The Cancer Genome Atlas (TCGA). Cox regression and Kaplan-Meier methods were used to correlate Nmut with chemotherapy response and outcome. Higher Nmut correlated with a better response to chemotherapy after surgery. In patients with mBRCA-associated cancer, low Nmut was associated with shorter progression-free survival (PFS) and overall survival (OS), independent of other prognostic factors in multivariate analysis. Patients with mBRCA-associated cancers and a high Nmut had remarkably favorable PFS and OS. The association with survival was similar in cancers with either BRCA1 or BRCA2 mutations. In cancers with wild-type BRCA, tumor Nmut was associated with treatment response in patients with no residual disease after surgery. CONCLUSIONS: Tumor Nmut was associated with treatment response and with both PFS and OS in patients with high-grade serous ovarian cancer carrying BRCA1 or BRCA2 mutations. In the TCGA cohort, low Nmut predicted resistance to chemotherapy, and for shorter PFS and OS, while high Nmut forecasts a remarkably favorable outcome in mBRCA-associated ovarian cancer. Our observations suggest that the total mutation burden coupled with BRCA1 or BRCA2 mutations in ovarian cancer is a genomic marker of prognosis and predictor of treatment response. This marker may reflect the degree of deficiency in BRCA-mediated pathways, or the extent of compensation for the deficiency by alternative mechanisms.

Dataset Information

Outcome of ovarian cancer after breast cancer in BRCA1 and BRCA2 mutation carriers.

Background

Methods

Results

Conclusions

Publications

Outcome of ovarian cancer after breast cancer in BRCA1 and BRCA2 mutation carriers.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets