Genetics and Molecular Pathology Laboratory, Medical school of Casablanca, Hassan II University, Casablanca, Morocco.
Mohammed VI Center for Cancer Treatment, Ibn Rochd University Hospital, Casablanca, Morocco.
Curr Drug Targets. 2020;21(10):962-973. doi: 10.2174/1389450121666200203162541.
Triple-negative breast cancer (TNBC) can be distinguished from other breast malignancies by the lack of expression of estrogen receptors (ER), progesterone receptors (PR) as well as human epidermal growth factor receptor 2 (HER2). TNBC is associated with adverse clinical outcomes and high risk of metastasis. Currently, several clinical and translational reports are focusing on developing targeted therapies for this aggressive cancer. In addition to approved targeted drugs such as poly(ADP-ribose) polymerase inhibitors (PARPi) and immune-checkpoint inhibitors, platinum-based chemotherapy is still a cornerstone therapeutic option in TNBC. However, despite the observed improved outcomes with platinum- based chemotherapy in TNBC, there is still a large proportion of patients who do not respond to this treatment, hence, the need for predictive biomarkers to stratify TNBC patients and therefore, avoiding unwanted toxicities of these agents. With the emergence of genetic testing, several recent studies suggested mutations in breast cancer susceptibility gene (BRCA) in TNBC patients as important predictors of outcomes. These mutations alter the homologous recombination repair (HRR) mechanisms leading to genomic instability. Consequently, sensitivity to platinum-based treatments in this subpopulation of TNBC patients may be explained by cell death enhanced by deoxyribonucleic acid (DNA) damage induced by these potent anticancer drugs. Through this paper, we review several recent studies on this topic to better understand the mechanisms and discuss the potential of BRCA mutational status as a predictive biomarker of platinum-based chemotherapy in TNBC.
三阴性乳腺癌（TNBC）可以通过缺乏雌激素受体（ER）、孕激素受体（PR）和人表皮生长因子受体 2（HER2）的表达来与其他乳腺恶性肿瘤区分开来。TNBC与不良的临床结局和高转移风险相关。目前，一些临床和转化研究都集中在为这种侵袭性癌症开发靶向治疗方法上。除了已批准的靶向药物，如多聚（ADP-核糖）聚合酶抑制剂（PARPi）和免疫检查点抑制剂，铂类化疗仍然是 TNBC 的基石治疗选择。然而，尽管在 TNBC 中观察到铂类化疗的疗效有所改善，但仍有很大一部分患者对这种治疗没有反应，因此需要预测性生物标志物来分层 TNBC 患者，从而避免这些药物的不必要毒性。随着基因检测的出现，最近的几项研究表明，TNBC 患者中乳腺癌易感基因（BRCA）的突变是预测结果的重要指标。这些突变改变了同源重组修复（HRR）机制，导致基因组不稳定。因此，这部分 TNBC 患者对铂类治疗的敏感性可以通过这些强效抗癌药物诱导的脱氧核糖核酸（DNA）损伤来增强细胞死亡来解释。通过本文，我们回顾了这一主题的几项最新研究，以更好地理解其机制，并讨论 BRCA 突变状态作为 TNBC 铂类化疗预测生物标志物的潜力。
