Incidence and outcome of BRCA mutations in unselected patients with triple receptor-negative breast cancer.
Incidence and outcome of BRCA mutations in unselected patients with triple receptor-negative breast cancer.
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DOI：
10.1158/1078-0432.ccr-10-2560
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发表时间：
2011-03-01
期刊：
影响因子：
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通讯作者：
Meric-Bernstam F
中科院分区：
文献类型：
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作者：
Gonzalez-Angulo AM;Timms KM;Liu S;Chen H;Litton JK;Potter J;Lanchbury JS;Stemke-Hale K;Hennessy BT;Arun BK;Hortobagyi GN;Do KA;Mills GB;Meric-Bernstam F
目的：探讨未选择的三阴性乳腺癌（TNBC）患者生殖系和体细胞BRCA1/2突变的发生率，并确定携带突变的预后意义。从77例TNBC和正常组织中获得DNA。从肿瘤和患者中对BRCA1/2外显子/侧翼区域进行测序，并将其分为突变型或野生型（WT）。从正常组织中重复测序以确定种系和体细胞突变。采用卡方法比较患者特征。采用Kaplan-Meier法估计生存率，并与log-rank进行比较。Cox比例风险模型拟合确定突变状态与预后的独立关联。中位年龄51岁（27-83岁）。15例（19.5%）患者有BRCA突变：12例（15.6%）BRCA1突变（1例体细胞突变），3例（3.9%）BRCA2突变。BRCA突变的患者往往比WT年轻，（p=0.005）。分级、组织学和分期与突变状态无关。中位随访时间为43个月（7-214个月），33例（42.9%）复发，35例（45.5%）死亡。WT患者5年无复发生存率为51.7%，突变患者为86.2% (p=0.031)；WT患者的5年总生存率为52.8%，突变患者为73.3%,（p=0.225）。调整后，与WT相比，BRCA突变患者的RFS明显更好（HR:0.19, 95% CI:0.045-0.79, p=0.016）。在这个未选择的TNBC队列中，我们发现BRCA突变发生率为19.5%。应与TNBC患者讨论基因检测。伴有BRCA突变的TNBC患者复发的风险显著降低。
To investigate the incidence of germline and somatic BRCA1/2 mutations in unselected patients with triple negative breast cancer (TNBC), and determine the prognostic significance of carrying a mutation. DNA was obtained from 77 TNBC and normal tissues. BRCA1/2 exons/flanking regions were sequenced from tumor and patients classified as mutant or wild type (WT). Sequencing was repeated from normal tissue to identify germline and somatic mutations. Patient characteristics were compared with chi-square. Survival was estimated by Kaplan-Meier method and compared with log-rank. Cox proportional hazards models were fit to determine the independent association of mutation status with outcome. Median age was 51 years (27-83 years). Fifteen patients (19.5%) had BRCA mutations: 12 (15.6%) in BRCA1 (one somatic), and 3 (3.9%) in BRCA2. Patients with BRCA mutations tended to be younger than WT, (p=0.005). Grade, histology and stage were not associated with mutation status. At a median follow-up of 43 months (7-214 months), there were 33 (42.9%) recurrences and 35 (45.5%) deaths. Five-year recurrence-free survival estimates were 51.7% for WT vs. 86.2% for patients with mutations, (p=0.031); and 5-year overall survival estimates were 52.8% for WT vs. 73.3% for patients with mutations, (p=0.225). After adjustment, patients with BRCA mutations had a significantly better RFS (HR:0.19, 95% CI:0.045-0.79, p=0.016) compared to WT. In this unselected cohort of TNBC, we found a 19.5% incidence of BRCA mutations. Genetic testing should be discussed with patients with TNBC. Patients with TNBC with BRCA mutations had a significantly lower risk of relapse.