Department of Breast Medical Oncology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030-4009, USA.
Clin Cancer Res. 2011 Mar 1;17(5):1082-9. doi: 10.1158/1078-0432.CCR-10-2560. Epub 2011 Jan 13.
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 versus 86.2% for patients with mutations, (P = 0.031); and 5-year overall survival estimates were 52.8% for WT versus 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 with 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.
研究未经选择的三阴性乳腺癌（TNBC）患者中胚系和体细胞 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，将其分类为突变型或野生型（WT）。从正常组织中重复测序以识别胚系和体细胞突变。用卡方检验比较患者特征。用 Kaplan-Meier 法估计生存情况，并与对数秩检验进行比较。拟合 Cox 比例风险模型以确定突变状态与结局的独立相关性。
中位年龄为 51 岁（27-83 岁）。15 例患者（19.5%）存在 BRCA 突变：BRCA1 中有 12 例（15.6%），BRCA2 中有 3 例（3.9%）。BRCA 突变患者的年龄小于 WT 患者（P=0.005）。分级、组织学和分期与突变状态无关。在中位随访 43 个月（7-214 个月）时，有 33 例（42.9%）复发，35 例（45.5%）死亡。WT 患者的 5 年无复发生存率估计值为 51.7%，突变患者为 86.2%（P=0.031）；WT 患者的 5 年总生存率估计值为 52.8%，突变患者为 73.3%（P=0.225）。经调整后，BRCA 突变患者的 RFS 显著更好（HR：0.19，95%CI：0.045-0.79，P=0.016）。
在本未经选择的 TNBC 队列中，我们发现 BRCA 突变的发生率为 19.5%。应与 TNBC 患者讨论基因检测。具有 BRCA 突变的 TNBC 患者复发风险显著降低。
