Low levels of BRCA1 mRNA were associated with longer survival in a retrospective

Microarray analysis has identified breast Hyperoside cancer subtypes with distinct gene expression profiles. These subtypes have been correlated with clinical outcome, and the impact of subtype on response to neoadjuvant chemotherapy has been evaluated in different series. BRCA1 expression can modulate cellular response to chemotherapy. Preclinical breast cancer studies suggest a role for BRCA1 in predicting response to DNA-damaging TBPB agents and taxane-based chemotherapy. Decreased BRCA1 mRNA expression in breast cancer cell lines, as determined by real-time quantitative polymerase chain reaction, enhances cisplatin sensitivity but leads to resistance to paclitaxel and vinorelbine via defective apoptotic response to these drugs, while the opposite phenomenon is observed in the presence of normal or high levels of BRCA1. In some sporadic breast cancers, the poor outcome associated with BRCA1 methylation and low expression levels could be explained by MYC amplification. Furthermore, several retrospective breast cancer studies have confirmed that carriers of BRCA1 mutations gained more benefit from DNAdamage-based chemotherapy. Low levels of BRCA1 mRNA were associated with longer survival in a retrospective cohort of lung cancer patients following cisplatin gemcitabine and in two retrospective cohorts of ovarian cancer patients treated with platinum-based chemotherapy. All these studies suggest that not only BRCA1 mutations but also reduced expression levels of BRCA1 mRNA could predict a benefit from DNA-damage-based chemotherapy. In clinical practice, fresh tumor tissue is not always available, and the recovery of mRNA from paraffin-embedded tissue is crucial. RT-QPCR permits quantitative and accurate measurement of gene mRNA expression. In a retrospective series of 86 breast cancer patients treated with neoadjuvant fluorouracil, epirubicin and cyclophosphamide, we evaluated response, time to progression and overall survival according to the simplified classification of breast cancer subtypes based on ER, PR and HER2.In addition, we examined CK5/6, vimentin and HER2 by immunohistochemistry; and HER2 by chromogenic in situ hybridization. Finally, in 41 patients for whom sufficient tumor tissue was available, intratumoral BRCA1 mRNA levels were assessed by RT-QPCR.