Clergue Océane, Jones Natalie, Sévenet Nicolas, Quenel-Tueux Nathalie, Debled Marc
Institut Bergonié, département d'oncologie médicale, 33076 Bordeaux cedex, France; Institut Bergonié, département de bio-pathologie, laboratoire de génétique moléculaire, unité d'oncogénétique, 33076 Bordeaux cedex, France.
Institut Bergonié, département de bio-pathologie, laboratoire de génétique moléculaire, unité d'oncogénétique, 33076 Bordeaux cedex, France.
Bull Cancer. 2015 Mar;102(3):245-55. doi: 10.1016/j.bulcan.2015.01.010. Epub 2015 Mar 7.
BRCA1 and BRCA2 mutations account for 40% of cancer predisposition gene mutations identified in the current French diagnostic setting. The proteins encoded by these genes are implicated in DNA repair pathways. As a result, loss of BRCA1 or BRCA2 function may modify chemo-sensitivity. This literature review aims to determine whether BRCA1 mutation status should influence the choice of systemic treatment in breast cancer. Fourteen articles and four abstracts from 12 retrospective analyses and 6 prospective studies were identified in the literature review. CMF-type and taxane-based protocols appear to be insufficiently effective, while anthracycline activity does not seem to be affected by BRCA1 status. BRCA1-mutated tumours appear to be highly sensitive to platinum, in both the neoadjuvant and metastatic setting. Olaparib, a PARP inhibitor, has only been evaluated in one study in metastatic patients, with promising results. The presence of a BRCA1 mutation can lead to an adaptation of therapies in the metastatic stages in breast cancer. The rapid identification of BRCA1 mutations and the adaptation of treatment according to this status in the (neo)adjuvant setting is likely to become a reality in the coming years.
在当前法国的诊断环境中,BRCA1和BRCA2突变占已鉴定出的癌症易感基因突变的40%。这些基因编码的蛋白质参与DNA修复途径。因此,BRCA1或BRCA2功能的丧失可能会改变化疗敏感性。这篇文献综述旨在确定BRCA1突变状态是否应影响乳腺癌全身治疗的选择。在文献综述中,从12项回顾性分析和6项前瞻性研究中鉴定出14篇文章和4篇摘要。CMF方案和紫杉烷类方案似乎疗效不足,而蒽环类药物的活性似乎不受BRCA1状态的影响。在新辅助和转移阶段,BRCA1突变的肿瘤似乎对铂类高度敏感。PARP抑制剂奥拉帕尼仅在一项针对转移性患者的研究中进行了评估,结果令人鼓舞。BRCA1突变的存在可导致乳腺癌转移阶段治疗方案的调整。在(新)辅助治疗中,快速鉴定BRCA1突变并根据该状态调整治疗方案在未来几年可能会成为现实。