BRCA1/2突变和同源重组修复缺陷(HRD)检测在乳腺癌中的临床研究进展

乳腺癌已成为发病率最高的癌症。DNA修复缺陷是乳腺癌最重要的特征之一。先前的研究表明，乳腺癌易感基因1/2(breast cancer susceptibility gene 1/2,BRCA1/2)突变是预测乳腺癌同源重组修复缺陷(homologous recombination deficiency, HRD)最主要的生物标志物，能识别铂类药物和多腺苷二磷酸核糖聚合酶(poly ADP ribose polymerase, PARP)抑制剂治疗的获益人群。美国食品药品监督管理局(FDA)已批准Olaparib和Talazoparib两种PARP抑制剂，用于BRCA1/2突变的早期和晚期乳腺癌的辅助治疗。但中国尚未获批。现有研究表明，一部分非BRCA1/2突变的乳腺癌患者也具有HRD特征，可以从铂类药物或PARP抑制剂中获益。本综述总结了涉及到BRCA1/2突变、同源重组修复(homologous recombination repair, HRR)基因突变和HRD状态检测的临床研究。阐明了各种检测方法在识别乳腺癌患者HRD状态和预测疗效方面的价值，并提出应尽快开发用于中国乳腺癌HR...

Clinical research progress of BRCA1/2 mutation and homologous recombination deficiency (HRD) detection in breast cancer

Breast cancer has become the most prevalent cancer,and DNA repair deficiency is one of the most important features of breast cancer.Previous studies have shown that breast cancer susceptibility gene 1/2 (BRCA1/2) mutations are the predominant biomarkers for predicting homologous recombination deficiency (HRD) in breast cancer because of the ability to identify the population that would benefit from platinum drugs and poly ADP ribose polymerase (PARP) inhibitors.The U.S.Food and Drug Administration (FDA) has approved Olaparib and Talazoparib,two PARP inhibitors,for the adjuvant treatment of early and advanced breast cancer with BRCA1/2 mutations.However,they have not yet been approved in China.Available studies suggest that a proportion of breast cancer patients with non-BRCA1/2 mutations also have HRD signatures and could benefit from platinum drugs or PARP inhibitors.This review summarizes the progress of clinical researches involving BRCA1/2 mutation,homologous recombination repair (HRR) gene mutation and HRD status detection.We elucidate the value of various assays in identifying HRD status and predicting efficacy in breast cancer patients,and suggest that HRD detection methods for breast cancer in China should be developed as soon as possible.