BRCA2 基因突变携带者罹患三阴性乳腺癌的转移风险。

Risk of metastasis in BRCA2 carriers diagnosed with triple-negative breast cancer.

机构信息

Graduate Program of A.C. Camargo Cancer Center, São Paulo, Brazil.

Medicine Course and Biomedical Sciences, Federal University of Fronteira Sul, Chapecó, Santa Catarina, Brazil.

出版信息

Cancer Med. 2023 Aug;12(15):16129-16141. doi: 10.1002/cam4.6267. Epub 2023 Jul 23.

DOI:10.1002/cam4.6267

PMID:37485802

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10469712/

Abstract

BACKGROUND

Triple-negative breast cancer (TNBC) is the neoplasia most associated with BRCA1 germline pathogenic variants (PV) and is more likely to develop metastases than the other breast cancer (BC) subtypes, mainly in the lungs and the central nervous system (CNS). Recently, BRCA2 carriers were shown to have a higher risk for developing CNS metastases. However, the patterns of recurrence and metastases of BRCA2 carriers with TNBC are unknown.

METHODS

TNBC patient data attending the A.C. Camargo Cancer Center, from 1998 through 2020, were verified either by medical records or by BRCA1/2 genetic testing carried out. Multivariable logistic regression models were fit to the data to assess the independent factors for bone and CNS metastases. Adjustment was done using all independent variables with p < 0.2 in the univariable Cox model to describe the relationship between the independent variables until time of death.

RESULTS

A total of 388 TNBC patients were evaluated. We identified PV in BRCA1/2 genes in 21% (82/388), being 17.7% (69/388) in BRCA1 and only 3.3% (13/388) in BRCA2. A total of 120 patients (31%) developed distant metastases. Bone or CNS metastases were observed in 40% and 60% of BRCA2 PV carriers (p = 0.155), respectively. The BRCA2 carriers tended to have a higher likelihood of developing bone metastases (OR, 4.06; 95% CI, 0.82-20.01; p = 0.085), when compared to BRCA1 carriers (OR, 0.6; 95% CI, 0.12-2.87; p = 0.528). BRCA2 carriers had an OR of 1.75 (95% CI, 0.33-9.14; p = 0.503) for CNS metastasis development, while BRCA1 carriers had an OR of 0.72 (95% CI, 0.23-2.23; p = 0.574).

CONCLUSIONS

Patients with TNBC and PV in the BRCA2 gene had higher frequencies of secondary bone involvement and CNS in the course of the disease. However, the BRCA2 PV did not represent an independent outcome predictor of metastases and overall survival. Efforts to increase the number of BRCA2 carriers among TNBC patients are crucial for determining their risk of developing bone and CNS metastases compared to BRCA2 noncarriers.

摘要

背景

三阴性乳腺癌（TNBC）与 BRCA1 种系致病性变异（PV）的关联最为密切，比其他乳腺癌（BC）亚型更有可能发生转移，主要转移部位是肺部和中枢神经系统（CNS）。最近，BRCA2 携带者发生 CNS 转移的风险更高。然而，BRCA2 携带者的 TNBC 复发和转移模式尚不清楚。

方法

通过病历或进行 BRCA1/2 基因检测，对 1998 年至 2020 年期间在 A.C. Camargo 癌症中心就诊的 TNBC 患者数据进行验证。使用多变量逻辑回归模型对数据进行分析，以评估骨转移和 CNS 转移的独立因素。使用单变量 Cox 模型中 p 值<0.2 的所有独立变量进行调整，以描述独立变量与死亡时间之间的关系。

结果

共评估了 388 例 TNBC 患者。我们在 BRCA1/2 基因中发现了 21%（82/388）的 PV，其中 BRCA1 为 17.7%（69/388），BRCA2 仅为 3.3%（13/388）。共有 120 例患者（31%）发生远处转移。BRCA2 PV 携带者中发生骨或 CNS 转移的比例分别为 40%和 60%（p=0.155）。与 BRCA1 携带者相比，BRCA2 携带者发生骨转移的可能性更高（OR，4.06；95%CI，0.82-20.01；p=0.085）。BRCA2 携带者发生 CNS 转移的 OR 为 1.75（95%CI，0.33-9.14；p=0.503），而 BRCA1 携带者的 OR 为 0.72（95%CI，0.23-2.23；p=0.574）。