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BRCA突变对早发性三阴性乳腺癌临床病理及治疗影响的见解

Insights Into the Impacts of BRCA Mutations on Clinicopathology and Management of Early-Onset Triple-Negative Breast Cancer.

作者信息

Ye Fugui, He Min, Huang Liang, Lang Guantian, Hu Xin, Shao Zhimin, Di Genhong, Cao Ayong

机构信息

Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.

Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

出版信息

Front Oncol. 2021 Jan 11;10:574813. doi: 10.3389/fonc.2020.574813. eCollection 2020.

Abstract

BACKGROUND

Little is known regarding the clinicopathologic characteristics, oncologic outcomes, and treatment strategies that could be ascribed to BRCA mutation in early-onset triple-negative breast cancer (eTNBC).

METHODS

eTNBC patients who underwent BRCA genetic testing were derived from our clinical database between 2012 and 2018. Differences in clinical features and pathologic characteristics were examined in groups divided by BRCA mutation status, and the contribution of germline mutations in conjunction with treatment modalities to survival outcomes was determined.

RESULTS

Of the 355 qualifying eTNBC patients, 67 (18.87%) were BRCA mutated and 288 (81.13%) were BRCA wild. Overall, median age at diagnosis was 34 years (range, 24-40 years) in the BRCA mutated subgroup and 35 years (range, 21-40 years) in BRCA wild. The majority of clinicopathologic parameters were parallel; however, tumor size ( = 0.07) and nuclear grade ( =0.08) tend to be more aggressive in the BRCA mutated subgroup. Compared with BRCA wild patients, BRCA mutated patients had a higher likelihood of receiving anthracyclines and taxane-based combination chemotherapy ( = 0.04) and tend to be lower tumor burden ( =0.01). After approximately 5-year median follow-up, the overall survival (OS) ( = 0.021) and breast cancer-specific survival (BCSS) ( = 0.004) in BRCA mutated patients were superior to those in their BRCA wild counterparts. Intriguingly, the clinical outcomes were comparable in patients with breast conserving surgery (BCS) regardless of BRCA mutations and in patients with BRCA mutations in spite of surgical schedules.

CONCLUSIONS

These results suggest that eTNBC patients with BRCA mutations are prone to better OS and BCSS, which might be largely attributed to more benefit from anthracyclines and taxane-based chemotherapy. The BCS procedure could be a safe alternative surgical option for eTNBC patients with BRCA mutations. Future studies with substantial numbers of participants are urgently needed to validate whether BRCA mutation eTNBC patients are more sensitive to chemotherapy.

摘要

背景

关于早发性三阴性乳腺癌(eTNBC)中BRCA突变的临床病理特征、肿瘤学结局和治疗策略,人们了解甚少。

方法

2012年至2018年间,接受BRCA基因检测的eTNBC患者来自我们的临床数据库。按BRCA突变状态分组,检查临床特征和病理特征的差异,并确定胚系突变与治疗方式对生存结局的影响。

结果

在355例符合条件的eTNBC患者中,67例(18.87%)为BRCA突变型,288例(81.13%)为BRCA野生型。总体而言,BRCA突变亚组的诊断中位年龄为34岁(范围24 - 40岁),BRCA野生型亚组为35岁(范围21 - 40岁)。大多数临床病理参数相似;然而,BRCA突变亚组的肿瘤大小(P = 0.07)和核分级(P = 0.08)往往更具侵袭性。与BRCA野生型患者相比,BRCA突变型患者接受蒽环类和紫杉类联合化疗的可能性更高(P = 0.04),且肿瘤负荷往往更低(P = 0.01)。经过约5年的中位随访,BRCA突变型患者的总生存期(OS)(P = 0.021)和乳腺癌特异性生存期(BCSS)(P = 0.004)均优于BRCA野生型患者。有趣的是,无论BRCA突变情况如何,保乳手术(BCS)患者的临床结局相当,且无论手术方案如何,BRCA突变患者的临床结局也相当。

结论

这些结果表明,BRCA突变的eTNBC患者倾向于有更好的总生存期和乳腺癌特异性生存期,这可能很大程度上归因于从蒽环类和紫杉类化疗中获益更多。对于BRCA突变的eTNBC患者,保乳手术可能是一种安全的替代手术选择。迫切需要大量参与者的未来研究来验证BRCA突变的eTNBC患者是否对化疗更敏感。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26ca/7829963/2fcfdd9ea824/fonc-10-574813-g001.jpg

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