中国BRCA1和BRCA2基因胚系突变乳腺癌的临床病理特征比较

  目的   比较中国人群中BRCA1和BRCA2基因两种突变状态的乳腺癌患者临床病理特征的差异。   方法   收集2003年10月至2015年5月北京大学肿瘤医院收治的8 627例连续的、未经家族史和年龄选择的原发性乳腺癌患者资料，经过基因测序共有521例患者携带BRCA1/2基因致病性胚系突变，其中BRCA1突变患者203例，BRCA2突变患者318例。对这些突变患者的临床病理参数进行回顾性分析。   结果   乳腺癌患者中BRCA2基因突变频率（3.7%）高于BRCA1（2.4%）。BRCA1突变者乳腺癌发病年龄比BRCA2突变者早（中位发病年龄:43.0岁 vs. 47.0岁，P<0.01）。BRCA1突变乳腺癌患者组织学分级Ⅲ级比例显著高于BRCA2突变患者（36.2% vs. 18.4%，P<0.01），三阴性乳腺癌（ER-/PR-/HER2-）比例也显著高于BRCA2突变者（59.2% vs. 15.4%，P<0.01）。BRCA2突变患者的腋窝淋巴结阳性比例高于BRCA1突变患者（41.8% vs. 29.6%，P<0.01）。   结论   中国BRCA1和BRCA2胚系突变乳腺癌的临床病理特征存在一定差异，提示BRCA1和BRCA2胚系突变对乳腺癌生物学行为的影响可能不同，为BRCA1和BRCA2胚系突变乳腺癌更加精准的临床管理提供依据。  

Comparison of clinicopathological characteristics between BRCA1 and BRCA2 mutation carriers among Chinese women with breast cancer

  Objective   To compare the clinicopathological characteristics between BRCA1 and BRCA2 mutation carriers among Chinese women with breast cancer.   Methods   BRCA1/2 genetic testing was performed on 8,627 patients with primary breast cancer at Peking University Cancer Hospital & Institute from October 2003 to May 2015. Overall, 521 BRCA1/2 pathogenic germline mutations were identified in this cohort, including 203 BRCA1 mutation carriers and 318 BRCA2 mutation carriers. The clinicopathological characteristics of these 521 patients were analyzed retrospectively.   Results   The prevalence of BRCA2 germline mutations (3.7%) was higher than that of BRCA1 germline mutations (2.4%) in this large, unselected cohort of Chinese patients with breast cancer. BRCA1 mutation carriers were significantly younger at time of breast cancer diagnosis than BRCA2 mutation carriers (median: 43.0 years vs.47.0 years, P<0.01).BRCA1 mutation carriers were more likely to have grade Ⅲ carcinomas than BRCA2 mutation carriers (36.2% vs.18.4%, P<0.01). Notably,BRCA1 mutation carriers exhibited a significantly higher proportion of triple negative breast cancer (ER-/PR-/HER2-) than BRCA2 mutation carriers (59.2% vs. 15.4%, P<0.01).BRCA2 mutation carriers were more likely to have axillary lymph node involvement than BRCA1 mutation carriers (41.8% vs.29.6%, P<0.01).   Conclusions   The clinicopathological characteristics between BRCA1 and BRCA2 mutation carriers among Chinese women with breast cancer were not similar, indicating an underlying different biological mechanism. The results provided the evidence for further precised clinical management of the BRCA1 and BRCA2 mutated breast cancer.