Predictive value of BRCA1 expression on the efficacy of chemotherapy based on anti-microtubule agents: a pooled analysis across different malignancies and agents

Background: Breast cancer susceptibility gene 1 (BRCA1) expression has been suggested as a predictor in anti-neoplastic treatment with anti-microtubule agents. However, the existing evidence is conflicting. Consulting the literature, we sought to examine the true impact of BRCA1 expression on the efficacy of anti-microtubule agents.

Methods: Medline by PubMed and Embase databases were searched for eligible studies. The primary endpoints were objective response rate (ORR) and progression free survival (PFS). Additional subgroup analyses stratified for detection methods, regimen, and patient origin were also performed.

Results: A total of 13 relevant studies involving a total of 1,490 cases were enrolled. Involved agents included paclitaxel, docetaxel and vinorelbine; Malignancies included non-small cell lung cancer, gastric cancer, esophageal carcinoma, ovarian carcinoma, malignant pleural mesothelioma, breast cancer, and small cell lung cancer. Through meta-analyses, we observed a potentially greater ORR in the population with high BRCA1 expression vs. low BRCA1 expression (OR 1.63, 95% CI: 0.92 to 2.88, P=0.09) but the heterogeneity is severe (P=0.01; I(2)=61%). Similar results were observed in PFS (high vs. low expression, HR 0.93, 95% CI: 0.75 to 1.15, P=0.49; heterogeneity, P<0.01, I(2)=75%). After stratification by testing methods, a significantly higher ORR in the population with high BRCA1 expression was shown in the subgroup using mRNA as a quantitative method (OR 2.90, 95% CI: 1.92 to 4.39, P<0.01; I(2)=0) whereas the difference in the subgroup using immunohistochemistry (IHC) was not significant (OR 0.60, 95% CI: 0.33 to 1.10, P=0.10; I(2)=0). Stratification by regimen (platinum-based vs. non platinum-based) and patient origin (Asian vs. Caucasian) did not reduce the heterogeneity.

Conclusions: Although the predictive value of BRCA1 expression on the anti-microtubule chemotherapy remained uncertain based on overall results, our exploratory analyses suggested that detection using mRNA might be a preferred technique, however, further validation is required to substantiate our findings.