Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Amsterdam, The Netherlands.
Division of Molecular Pathology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Amsterdam, The Netherlands.
J Natl Cancer Inst. 2017 Aug 1;109(8). doi: 10.1093/jnci/djw329.
BACKGROUND: The primary aim of the study was to investigate prognosis and long-term survival in young breast cancer patients with a BRCA1 or BRCA2 germline mutation compared with noncarriers. The secondary aim was to investigate whether differences in survival originate from associations with tumor characteristics, second cancers, and/or treatment response. METHODS: We established a cohort of invasive breast cancer patients diagnosed younger than age 50 years in 10 Dutch hospitals between 1970 and 2003. BRCA1/2 testing of most prevalent mutations was mainly done using DNA isolate from formalin-fixed paraffin-embedded nontumor tissue. Survival estimates were derived using Cox regression and competing risk models. RESULTS: In 6478 breast cancer patients, we identified 3.2% BRCA1 and 1.2% BRCA2 mutation carriers. BRCA1 mutation carriers had a worse overall survival independent of clinico-pathological/treatment characteristics, compared with noncarriers (adjusted hazard ratio [HR] = 1.20, 95% confidence interval [CI] = 0.97 to 1.47), though only statistically significant in the first five years of follow-up (adjusted HR = 1.40, 95% CI = 1.07 to 1.84). A large part of the worse survival was explained by incidence of ovarian cancers. Breast cancer-specific, disease-free, and metastasis-free survival results were less pronounced and mostly statistically nonsignificant but in the same direction with those of overall survival. Overall survival was worse, although not statistically significantly, within the ER-negative or ER-positive, grade 3, and small tumor subgroups. The worse survival was most pronounced in non-chemotherapy-treated patients (adjusted HR = 1.54, 95% CI = 1.08 to 2.19). Power for BRCA2 mutation carriers was limited; only after five years' follow-up overall survival was worse (adjusted HR = 1.47, 95% CI = 1.00 to 2.17). CONCLUSIONS: BRCA1/2 mutation carriers diagnosed with breast cancer before age 50 years are prone to a worse survival, which is partly explained by differences in tumor characteristics, treatment response, and second ovarian cancers.
背景：本研究的主要目的是比较携带 BRCA1 或 BRCA2 种系突变的年轻乳腺癌患者与非携带者的预后和长期生存情况。次要目的是研究生存差异是否源于与肿瘤特征、第二癌症和/或治疗反应的关联。
方法：我们建立了一个队列，纳入了 1970 年至 2003 年期间在 10 家荷兰医院诊断为 50 岁以下的浸润性乳腺癌患者。最常见突变的 BRCA1/2 检测主要使用福尔马林固定石蜡包埋非肿瘤组织的 DNA 进行。使用 Cox 回归和竞争风险模型得出生存估计。
结果：在 6478 例乳腺癌患者中，我们发现 3.2%为 BRCA1 突变携带者，1.2%为 BRCA2 突变携带者。BRCA1 突变携带者的总体生存情况较差，独立于临床病理/治疗特征，与非携带者相比（调整后的危险比[HR] = 1.20，95%置信区间[CI] = 0.97 至 1.47），尽管仅在前五年的随访中具有统计学意义（调整后的 HR = 1.40，95%CI = 1.07 至 1.84）。较差的生存结果在很大程度上归因于卵巢癌的发生率。乳腺癌特异性、无病和无转移生存结果则不太明显，且大多数无统计学意义，但与总体生存结果一致。在 ER 阴性或阳性、分级 3 和肿瘤较小的亚组中，总体生存情况虽然无统计学意义，但较差。在未接受化疗治疗的患者中，生存情况更差（调整后的 HR = 1.54，95%CI = 1.08 至 2.19）。BRCA2 突变携带者的生存结果因样本量限制而无统计学意义；仅在五年随访后，总体生存情况较差（调整后的 HR = 1.47，95%CI = 1.00 至 2.17）。
结论：50 岁以下诊断为乳腺癌的 BRCA1/2 突变携带者有较差的生存趋势，这部分归因于肿瘤特征、治疗反应和第二卵巢癌的差异。
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