Data are scarce on the role of pathogenic germline variants inBRCA1andBRCA2(gBRCAm) in subtype-specific survival in young women who develop breast cancer under the age of 40. This retrospective, real-world cohort study assessed the distant disease-free survival (DDFS) and overall survival (OS) of young women diagnosed with breast cancer between 2008 and 2019 while taking into consideration the interaction of clinical subtypes and the gBRCA status. Among 473 women, HR+/Her2− was the most common subtype (49.0%), followed by TNBC (31.3%), HR+/Her2+ (13.7%), and Her2+/HR− (5.9%). The gBRCA status was known for 319 cases (gBRCAwt (wild-type – without pathogenic variants inBRCA1orBRCA2): 204, gBRCA1m: 83, gBRCA2m: 31, 1 patient with both). The distribution of clinical subtypes varied depending on the gBRCA status (p< 0.001). In survival analysis with a median follow-up of 43 months, the unadjusted DDFS and OS were worse for gBRCAwt TNBC compared to both HR+ subtypes, but not for gBRCAm TNBC patients. T-stage, nodal involvement, and the gBRCA status were identified as significant for survival in TNBC. In TNBC, gBRCAm was associated with better DDFS and OS than gBRCAwt (5-year DDFS 81.4% vs. 54.3%,p= 0.012 and 5-year OS 96.7% vs. 62.7%,p< 0.001). In contrast, in HR+/Her2− patients, gBRCAm patients showed a tendency for worse survival, though not statistically significant. Subtype-specific survival in young women with breast cancer needs to be evaluated in interaction with the gBRCA status. For TNBC, gBRCAm is of favorable prognostic value for overall survival, while patients with gBRCAwt TNBC need to be considered to have the highest risk for adverse survival outcomes.
关于BRCA1和BRCA2致病性胚系变异（gBRCAm）在40岁以下年轻乳腺癌患者亚型特异性生存中的作用，目前数据较为缺乏。这项回顾性真实世界队列研究评估了2008年至2019年间确诊乳腺癌的年轻女性的无远处转移生存期（DDFS）和总生存期（OS），同时考虑了临床亚型与gBRCA状态的交互作用。在473例患者中，HR+/Her2−是最常见的亚型（49.0%），其次为三阴性乳腺癌（31.3%）、HR+/Her2+（13.7%）和Her2+/HR−（5.9%）。其中319例已知gBRCA状态（gBRCA野生型204例，gBRCA1突变83例，gBRCA2突变31例，1例为双基因突变）。临床亚型分布因gBRCA状态不同而存在显著差异（p<0.001）。在中位随访43个月的生存分析中，未经校正的DDFS和OS显示gBRCA野生型三阴性乳腺癌患者预后差于两种HR+亚型，但gBRCA突变型三阴性乳腺癌患者未出现此现象。T分期、淋巴结转移状态和gBRCA状态被确定为影响三阴性乳腺癌患者生存的重要因素。在三阴性乳腺癌中，gBRCA突变患者较野生型患者具有更好的DDFS和OS（5年DDFS：81.4% vs. 54.3%，p=0.012；5年OS：96.7% vs. 62.7%，p<0.001）。相反，在HR+/Her2−患者中，gBRCA突变患者虽呈现生存较差的趋势，但未达统计学显著性。年轻乳腺癌患者的亚型特异性生存需结合gBRCA状态进行综合评估。对于三阴性乳腺癌，gBRCA突变提示预后良好，而gBRCA野生型三阴性乳腺癌患者应被视为具有最高不良生存风险的人群。
肿瘤(癌症)患者之家