The aim of the current study was to investigate the role of BRCA1 gene aberrations in sporadic triple-negative breast cancer (TNBC) and its impact on anthracycline-based therapy. BRCA1 promoter methylation was analyzed in 70 TNBC and compared with the clinical and pathologic characteristics. As a control group, we used 70 patients with non-TNBC. BRCA1 promoter methylation was observed in 65.2 % of patients and was similar in both groups. BRCA1 promoter methylation was associated with decreased intensity of BRCA1 protein expression (P = 0.002) and significant increase of median disease-free survival (DFS) of TNBC patients receiving adjuvant anthracycline-based chemotherapy (P = 0.001). Multivariate analysis revealed that BRCA1 promoter methylation remains a favorable factor in regard to DFS (HR 0.224; 95 % CI 0.092-0.546, P = 0.001) in TNBC after adjustment for other prognostic factors. In contrast, in non-TNBC, BRCA1 promoter methylation was not associated with any clinical and pathologic parameters. BRCA1 promoter methylation is a common mechanism of BRCA1 gene aberration in sporadic breast cancer and is predictive for better response to anthracycline-based therapies.

译文

本研究的目的是研究BRCA1基因畸变在散发性三阴性乳腺癌 (TNBC) 中的作用及其对蒽环类药物治疗的影响。在70个TNBC中分析了BRCA1启动子甲基化,并与临床和病理特征进行了比较。作为对照组,我们使用了70例非TNBC患者。在65.2% 患者中观察到BRCA1启动子甲基化,两组相似。BRCA1启动子甲基化与接受基于蒽环类药物的辅助化疗的TNBC患者BRCA1蛋白表达强度降低 (P = 0.002) 和中位无病生存期 (DFS) 显著增加 (P = 0.001) 相关。多变量分析显示,在调整其他预后因素后,BRCA1启动子甲基化仍然是TNBC中DFS (HR 0.224; 95% CI 0.092-0.546,P = 0.001) 的有利因素。相反,在非TNBC中,BRCA1启动子甲基化与任何临床和病理参数无关。BRCA1启动子甲基化是散发性乳腺癌中BRCA1基因畸变的常见机制,并且可以预测对基于蒽环类药物的治疗有更好的反应。

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