Efficacy of Neoadjuvant Cisplatin in Triple-Negative Breast Cancer
Efficacy of Neoadjuvant Cisplatin in Triple-Negative Breast Cancer
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DOI：
10.1200/jco.2009.22.4725
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发表时间：
2010-03-01
影响因子：
45.3
通讯作者：
Garber, Judy E.
中科院分区：
文献类型：
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作者：
Silver, Daniel P.;Richardson, Andrea L.;Garber, Judy E.
目的顺铂是一种不常用于乳腺癌治疗的化疗药物。顺铂作为一种DNA交联剂，可能是治疗遗传性BRCA 1突变乳腺癌的有效药物。由于散发性三阴性乳腺癌（TNBC）和BRCA 1相关乳腺癌具有共同的发病机制，我们在TNBC中进行了顺铂的新辅助试验，并探索了特定的生物标志物以确定反应的预测因子。患者和方法28名患有缺乏雌激素和孕激素受体以及HER 2/Neu（TNBC）的II或III期乳腺癌的妇女入选并接受顺铂75 mg/m2每21天一次的4个周期治疗。在确定性手术后，患者根据其治疗医生接受标准辅助化疗和放疗。临床和病理治疗反应进行了评估，并预处理肿瘤样本进行了评价选定的biomarkers.ResultsSix（22%）的28例患者实现病理完全反应，包括两个BRCA 1生殖系突变的患者，18（64%）患者有临床完全或部分反应。14例（50%）患者表现出良好的病理学反应（Miller-Payne评分为3、4或5），10例有轻微反应（Miller-Payne评分为1或2），4例（14%）进展。所有TNBC通过分层聚类与参考基底样肿瘤聚类。与良好的顺铂反应相关的因素包括年轻（P = 0.001），低BRCA 1 mRNA表达（P = 0.03），BRCA 1启动子甲基化（P = 0.04），p53无义或移码突变（P = 0.01），和E2 F3激活的基因表达特征（P = 0.03）。BRCA 1表达降低可识别顺铂敏感的TNBC亚群。其他生物标志物在预测顺铂反应方面显示出希望。J Clin Oncol 28：1145-1153. (C)2010年美国临床肿瘤学会
PurposeCisplatin is a chemotherapeutic agent not used routinely for breast cancer treatment. As a DNA cross-linking agent, cisplatin may be effective treatment for hereditary BRCA1-mutated breast cancers. Because sporadic triple-negative breast cancer (TNBC) and BRCA1-associated breast cancer share features suggesting common pathogenesis, we conducted a neoadjuvant trial of cisplatin in TNBC and explored specific biomarkers to identify predictors of response.Patients and MethodsTwenty-eight women with stage II or III breast cancers lacking estrogen and progesterone receptors and HER2/Neu (TNBC) were enrolled and treated with four cycles of cisplatin at 75 mg/m(2) every 21 days. After definitive surgery, patients received standard adjuvant chemotherapy and radiation therapy per their treating physicians. Clinical and pathologic treatment response were assessed, and pretreatment tumor samples were evaluated for selected biomarkers.ResultsSix (22%) of 28 patients achieved pathologic complete responses, including both patients with BRCA1 germline mutations; 18 (64%) patients had a clinical complete or partial response. Fourteen (50%) patients showed good pathologic responses (Miller-Payne score of 3, 4, or 5), 10 had minor responses (Miller-Payne score of 1 or 2), and four (14%) progressed. All TNBCs clustered with reference basal-like tumors by hierarchical clustering. Factors associated with good cisplatin response include young age (P = .001), low BRCA1 mRNA expression (P = .03), BRCA1 promoter methylation (P = .04), p53 nonsense or frameshift mutations (P = .01), and a gene expression signature of E2F3 activation (P = .03).ConclusionSingle-agent cisplatin induced response in a subset of patients with TNBC. Decreased BRCA1 expression may identify subsets of TNBCs that are cisplatin sensitive. Other biomarkers show promise in predicting cisplatin response. J Clin Oncol 28: 1145-1153. (C) 2010 by American Society of Clinical Oncology