The predictive value of BRCA1/2 mRNA expression for response to neoadjuvant chemotherapy in BRCA negative breast cancers

Summary

It is well known that BRCA1 and BRCA2 play a central role in DNA repair, but the relationship between BRCA1 and BRCA2 mRNA expression and response to neoadjuvant chemotherapy in sporadic breast cancer patients has not been well established. Here, we investigate the association between BRCA1 or BRCA2 mRNA expression levels and pathological response in 674 BRCA1/2 mutation-negative breast cancer patients who received neoadjuvant chemotherapy. BRCA1and BRCA2 mRNA expression were assessed using quantitative real-time polymerase chain reaction in core biopsy breast cancer tissue obtained prior to the initiation of neoadjuvant chemotherapy. A total 129 patients (19.1%) achieved pCR (pathologic complete response) after neoadjuvant chemotherapy. Among patients treated with anthracycline-based chemotherapy (n=531), BRCA1 mRNA low expression patients had significantly higher pCR rate than intermediate or high BRCA1 mRNA expression groups (24.6% vs 16.8% or 14.0%, p=0.031) and retained borderline significance (OR=1.54, 95% CI=0.93–2.56, P=0.094) in multivariate analysis. Among the 129 patients who received taxane-based regimen, pCR rate showed no differences in BRCA1 low, intermediate, and high mRNA level subgroups (19.6%, 26.8% and 21.4%, respectively; p=0.71). BRCA2 mRNA level was not associated with pCR rate in the anthracyline-based treated subgroup (p=0.60) or the taxane-based regimen subgroup (p=0.82). Taken together, our findings suggested that BRCA1 mRNA expression could be used as a predictive marker in BRCA1/2 mutation-negative breast cancer patients who received neoadjuvant anthracycine-based treatment.

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