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

• Published in: Cancer science 2018-01, Vol.109 (1), p.166-173
• Main Authors: Xu, Ye, Ouyang, Tao, Li, Jinfeng, Wang, Tianfeng, Fan, Zhaoqing, Fan, Tie, Lin, Benyao, Xie, Yuntao
• Format: Article
• Language: English
• Subjects: Anthracyclines - administration & dosage; Anthracyclines - pharmacology; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - pharmacology; BRCA1 gene; BRCA1 Protein - genetics; BRCA2 gene; BRCA2 Protein - genetics; breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Bridged-Ring Compounds - administration & dosage; Bridged-Ring Compounds - pharmacology; Female; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic - drug effects; Humans; mRNA expression; neoadjuvant chemotherapy; Neoadjuvant Therapy; Original; Real-Time Polymerase Chain Reaction; Taxoids - administration & dosage; Taxoids - pharmacology; Treatment Outcome
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.13426

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. BRCA1 and 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 pathological complete response (pCR) after neoadjuvant chemotherapy. Among patients treated with anthracycline‐based chemotherapy (n = 531), BRCA1 mRNA low expression patients had a significantly higher pCR rate than intermediate or high BRCA1 mRNA expression groups (24.6% vs 16.8% or 14.0%, P = .031) and retained borderline significance (OR = 1.54, 95% CI = 0.93‐2.56, P = .094) in multivariate analysis. Among the 129 patients who received a 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 = .71). BRCA2 mRNA level was not associated with pCR rate in the anthracyline‐based treated subgroup (P = .60) or the taxane‐based regimen subgroup (P = .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 anthracycline‐based treatment. BRCA1 and BRCA2 genes play important roles in DNA repair, cell cycle checkpoint control, transcriptional regulation, and ubiquitination, so their deficiencies can impact the response of cancer cells to chemotherapy drugs. In this study,we found that BRCA1 mRNA low expression was associated with good pCR in BRCA1/2 mutation‐negative patients.