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The role of BRCA status on prognosis in patients with triple-negative breast cancer.

ABSTRACT: Studies have showed that dysfunction in the breast cancer susceptibility gene (BRCA) is associated with triple-negative breast cancer (TNBC); however, its effect on patient survival remains controversial. We investigated the distribution of BRCA1/2 mutations in unselected Chinese patients with TNBC and explored their roles in prognosis. Then a systematic review and meta-analysis were performed to evaluate the prognostic role of BRCA dysfunction, including BRCA1/2 germline/somatic mutations, BRCA1 promoter methylation, and low BRCA1 protein expression in TNBC patients. Pooled hazard ratios with 95% confidence intervals were estimated to determine the association between BRCA dysfunction and survival. Our results showed a high frequency of BRCA1/2 mutations, especially germline BRCA1 variants, were associated with bilateral breast cancer. Although no correlations were found between BRCA1/2 mutations and recurrence-free survival (RFS) or overall survival (OS). In the meta-analysis, patients with BRCA1 promoter methylation showed poor OS. However, there was a favorable impact on disease free survival (DFS) for TNBC patients with BRCA1 promoter methylation when received adjuvant-chemotherapy. In conclusion, BRCA1/2 mutations were associated with bilateral breast cancer and BRCA1 promoter methylation may have a prognostic effect on TNBC.

SUBMITTER: Xie Y

PROVIDER: S-EPMC5675622 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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The role of BRCA status on prognosis in patients with triple-negative breast cancer.

Xie Yuxin Y Gou Qiheng Q Wang Qianqian Q Zhong Xiaorong X Zheng Hong H

Oncotarget 20170803 50

Studies have showed that dysfunction in the breast cancer susceptibility gene (BRCA) is associated with triple-negative breast cancer (TNBC); however, its effect on patient survival remains controversial. We investigated the distribution of BRCA1/2 mutations in unselected Chinese patients with TNBC and explored their roles in prognosis. Then a systematic review and meta-analysis were performed to evaluate the prognostic role of BRCA dysfunction, including BRCA1/2 germline/somatic mutations, BRCA ...[more]

PMID: 29152070

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Project description:BACKGROUND:Anti-Androgen Receptor (AR) therapy holds promise for a subset of AR expressing triple-negative breast cancer (TNBC) patients. However, current AR assays are suboptimal in detecting the dynamic range of AR expression, contributing to its controversial role in TNBC disease prognosis. This study is aimed at evaluating the feasibility of qRT-PCR to sensitively and robustly detect AR mRNA levels for prognostication. METHODS:mRNA expression profiling was performed on FFPE blocks from a retrospective cohort of 101 TNBC patients using qRT-PCR and compared with AR protein expression by immunohistochemistry . Statistical analyses included Spearman's rank correlation, Chi-square and Kaplan-Meier analyses. Distant Metastasis Free Survival was used as the end point in survival analysis. RESULTS:AR mRNA expression was observed in 34/101 patients (34%) whereas 12/80 cases (15%) were positive by IHC. qRT-PCR could thus detect more AR positive patients as compared to IHC, with 75% (9/12) concordance between the two methods. Co-expression of GATA3 and FOXA1 mRNA was observed in 85 and 88% of AR mRNA positive tumors, respectively. AR mRNA positivity was significantly correlated with age at disease onset (p?=?0.02), high FOXA1/GATA3 (p?<?0.05) and distant recurrence. AR mRNA positive patients had poorer DMFS (43%; p?=?0.002). DMFS dropped further to 26% (p?=?0.006) in AR (+)/high FOXA1/GATA3 patients. AR mRNA expression together with node positivity had the worst DMFS (23%; p?<?0.0001) compared to patients who were either positive for any one of these, or negative for both AR and node status. Low Ki67 mRNA with AR mRNA positivity also had poorer DMFS (39%; p?=?0.001) compared to patients expressing low Ki67 with no AR mRNA expression. CONCLUSION:qRT-PCR was more sensitive and reliable in detecting the dynamic expression levels of AR compared to IHC and this variation could be explained by the higher sensitivity of the former method. High AR mRNA expression was strongly associated with expression of AR protein, high FOXA1/GATA3 mRNA, and with poor prognosis. qRT-PCR was more efficient in detecting the AR positive cases compared to IHC. A distinct signature involving high GATA3/FOXA1, low Ki67, and node positivity in AR mRNA positive tumors correlated with poor prognosis. Thus, AR mRNA screening can serve as an effective prognostic marker along with offering potential targeted therapy options for TNBC.

Dataset Information

The role of BRCA status on prognosis in patients with triple-negative breast cancer.

Publications

The role of BRCA status on prognosis in patients with triple-negative breast cancer.

Similar Datasets

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