Kostov Aleksandar M, Jensen Maj-Britt, Ejlertsen Bent, Thomassen Mads, Rossing Maria, Pedersen Inge S, Petersen Annabeth H, Christensen Lise Lotte, Wadt Karin A W, Berrocal-Almanza Luis C, Miranda Miguel, Lænkholm Anne-Vibeke
Department of Surgical Pathology, Zealand University Hospital, Sygehusvej 9-11, 4000, Roskilde, Denmark.
Danish Breast Cancer Cooperative Group, Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Breast Cancer Res Treat. 2025 May 23. doi: 10.1007/s10549-025-07726-2.
PURPOSE: To report the rates of risk-reducing surgery (RRS) following germline testing for BRCA1/2 (likely) pathogenic variants (BRCApv) and to assess the impact of RRS and BRCA status on survival after surgical treatment for unilateral breast cancer (BC). METHODS: We identified 7145 women with BC (2000-2017), a BRCA test and median follow-up of 10.8 years from the Danish Breast Cancer Cooperative Group's clinical database. Distant recurrence-free (DRFS) and overall survival (OS) according to BRCA status were evaluated using the Kaplan-Meier method. Hazard ratios (HR) for BRCApv vs. BRCA wild-type, contralateral risk-reducing mastectomy (CRRM), and risk-reducing bilateral salpingo-oophorectomy (RRBSO), including interaction tests, were estimated using multivariable Cox models. RESULTS: Among BRCA1pv carriers (n = 403), CRRM rates were higher than in BRCA2pv (n = 317) (66% vs. 52%, p < 0.001) and more likely to receive timely testing, i.e., within 6 months of BC diagnosis (75% vs. 52%, p = 0.004). Regarding RRBSO rates, no differences were observed. CRRM was associated with significantly improved DRFS (HR = 0.63, 95% CI 0.51-0.78) and OS (HR = 0.64, 95% CI 0.51-0.82), independently of BRCA status and age. RRBSO was associated with improved OS only in BRCApv carriers, specifically, those aged ≥ 50 years (HR = 0.44, 95% CI 0.26-0.75). BRCApv (irrespective of affected gene) was associated with worse DRFS (HR = 1.31, 95% CI 1.06-1.63); however, this was only evident after 2 years of follow-up (HR = 1.53, 95% CI 1.22-1.93). BRCApv was not significantly associated with worse OS (HR = 1.25, 95%CI 0.98-1.58). CONCLUSION: Timely germline testing at BC diagnosis might increase CRRM rates in BRCApv carriers, thereby improving survival.
目的:报告对BRCA1/2(可能)致病变异(BRCApv)进行种系检测后进行降低风险手术(RRS)的比例,并评估RRS和BRCA状态对单侧乳腺癌(BC)手术治疗后生存的影响。 方法:我们从丹麦乳腺癌合作组的临床数据库中识别出7145例患有BC(2000 - 2017年)、接受过BRCA检测且中位随访时间为10.8年的女性。采用Kaplan-Meier方法评估根据BRCA状态的远处无复发生存期(DRFS)和总生存期(OS)。使用多变量Cox模型估计BRCApv与BRCA野生型、对侧降低风险乳房切除术(CRRM)和降低风险双侧输卵管卵巢切除术(RRBSO)的风险比(HR),包括交互作用检验。 结果:在BRCA1pv携带者(n = 403)中,CRRM比例高于BRCA2pv携带者(n = 317)(66%对52%,p < 0.001),并且更有可能接受及时检测,即在BC诊断后6个月内(75%对52%,p = 0.004)。关于RRBSO比例,未观察到差异。CRRM与显著改善的DRFS(HR = 0.63,95%CI 0.51 - 0.78)和OS(HR = 0.64,95%CI 0.51 - 0.82)相关,独立于BRCA状态和年龄。RRBSO仅在BRCApv携带者中与改善的OS相关,具体而言,是年龄≥50岁的携带者(HR = 0.44,95%CI 0.26 - 0.75)。BRCApv(无论受影响的基因)与更差的DRFS相关(HR = 1.31,95%CI 1.06 - 1.63);然而,这仅在随访2年后才明显(HR = 1.53,95%CI 1.22 - 1.93)。BRCApv与更差的OS无显著关联(HR = 1.25,95%CI 0.98 - 1. .58)。 结论:BC诊断时及时进行种系检测可能会提高BRCApv携带者的CRRM比例,从而改善生存。
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