Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Breast Center, Peking University Cancer Hospital & Institute, Beijing, PR China.
Ann Oncol. 2013 Jun;24(6):1498-505. doi: 10.1093/annonc/mdt011. Epub 2013 Feb 13.
BRCA1 function is inactivated through BRCA1 promoter methylation in a substantial number of triple-negative breast cancers. We investigated the impact of BRCA1-methylation status on the efficacy of adjuvant chemotherapy in patients with triple-negative breast cancer or with non-triple-negative breast cancer.
BRCA1 promoter methylation was assessed in 1163 unselected breast cancer patients. Methylation was evaluated using a methylation-specific PCR (MSP) assay.
In the subgroup of 167 triple-negative breast cancer patients who received adjuvant chemotherapy, patients with BRCA1-methylated tumors had a superior 10-year disease-free survival (DFS)(78% versus 55%, P = 0.009) and 10-year disease-specific survival (DSS) (85% versus 69%, P = 0.024) than those with BRCA1-unmethylated tumors, and BRCA1 methylation was an independent favorable predictor of DFS and DSS in a multivariate analysis in this subgroup [DFS: hazard ratio (HR) = 0.45; 95% confidence interval (CI) 0.24-0.84; P = 0.019; DSS: HR = 0.43; 95% CI = 0.19-0.95; P = 0.044]. In contrast, in 675 non-triple-negative breast cancer patients who received adjuvant chemotherapy, BRCA1 methylation was an unfavorable predictor of DFS and DSS in univariate analysis (DFS: HR = 1.56; 95% CI 1.16-2.12; P = 0.003; DSS: HR = 1.53; 95% CI = 1.05-2.21; P = 0.026).
Triple-negative breast cancer patients with BRCA1-methylated tumors are sensitive to adjuvant chemotherapy and have a favorable survival compared with patients with BRCA1-unmethylated triple-negative tumors.
BRCA1 功能通过 BRCA1 启动子甲基化在大量三阴性乳腺癌中失活。我们研究了 BRCA1-甲基化状态对三阴性乳腺癌或非三阴性乳腺癌患者辅助化疗疗效的影响。
在 1163 例未经选择的乳腺癌患者中评估了 BRCA1 启动子甲基化。使用甲基化特异性 PCR（MSP）测定评估甲基化。
在接受辅助化疗的 167 例三阴性乳腺癌患者亚组中，BRCA1 甲基化肿瘤患者的 10 年无病生存率（DFS）（78%比 55%，P = 0.009）和 10 年疾病特异性生存率（DSS）（85%比 69%，P = 0.024）优于 BRCA1 未甲基化肿瘤，并且在该亚组的多变量分析中，BRCA1 甲基化是 DFS 和 DSS 的独立有利预测因子[DFS：风险比（HR）= 0.45；95%置信区间（CI）0.24-0.84；P = 0.019；DSS：HR = 0.43；95% CI = 0.19-0.95；P = 0.044]。相比之下，在接受辅助化疗的 675 例非三阴性乳腺癌患者中，BRCA1 甲基化在单变量分析中是 DFS 和 DSS 的不利预测因子（DFS：HR = 1.56；95% CI 1.16-2.12；P = 0.003；DSS：HR = 1.53；95% CI = 1.05-2.21；P = 0.026）。
BRCA1 甲基化的三阴性乳腺癌患者对辅助化疗敏感，与 BRCA1 未甲基化的三阴性肿瘤患者相比，生存情况良好。
