Clinical Behavior of Breast Cancer in Young BRCA Carriers and Prediagnostic Awareness of Germline BRCA Status.

IF 42.1 1区医学 Q1 ONCOLOGY

Journal of Clinical Oncology Pub Date : 2025-05-10 Epub Date: 2025-02-24 DOI:10.1200/JCO-24-01334

Matteo Lambertini, Eva Blondeaux, Loredana M Tomasello, Elisa Agostinetto, Anne-Sophie Hamy, Hee Jeong Kim, Maria Alice Franzoi, Rinat Bernstein-Molho, Florentine Hilbers, Katarzyna Pogoda, Hans Wildiers, Jyoti Bajpai, Michail Ignatiadis, Halle C F Moore, Ann H Partridge, Kelly-Anne Phillips, Angela Toss, Christine Rousset-Jablonski, Carmen Criscitiello, Tiphaine Renaud, Alberta Ferrari, Shani Paluch-Shimon, Robert Fruscio, Wanda Cui, Stephanie M Wong, Claudio Vernieri, Kathryn J Ruddy, Maria Vittoria Dieci, Alexios Matikas, Mariya Rozenblit, Cynthia Villarreal-Garza, Laura De Marchis, Fabio Puglisi, Kenny A Rodriguez-Wallberg, Francois P Duhoux, Luca Livraghi, Marco Bruzzone, Luca Boni, Judith Balmaña

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引用次数: 0

Abstract

Purpose: To investigate the clinical behavior of breast cancer in young BRCA carriers according to the specific BRCA gene (BRCA1 v BRCA2) and the association of the timing of genetic testing (before v at diagnosis) with prognosis.

Methods: This was an international, multicenter, hospital-based, retrospective cohort study that included 4,752 patients harboring germline pathogenic/likely pathogenic variants (PVs) in BRCA1 or BRCA2, who were diagnosed with stage I-III invasive breast cancer at 40 years or younger between January 2000 and December 2020 in 78 centers worldwide (ClinicalTrials.gov identifier: NCT03673306).

Results: Compared with BRCA2 carriers (n = 1,683), BRCA1 carriers (n = 3,069) had more frequently hormone receptor-negative (74.4% v 15.5%) and high-grade (77.5% v 49.1%) tumors. Similar outcomes were observed in BRCA1 and BRCA2 carriers but with a different pattern and risk of disease-free survival events over time. Compared with patients tested for BRCA at diagnosis (ie, between 2 months before and up to 6 months after diagnosis; n = 1,671), those tested before diagnosis (ie, any time up to 2 months before diagnosis; n = 411) had smaller tumors (T1: 61.3% v 32.4%), less nodal involvement (N0: 65.9% v 50.8%), less frequently received chemotherapy (84.4% v 92.9%), and axillary dissection (37.5% v 47.4%). Patients tested before diagnosis had better overall survival (OS; unadjusted hazard ratio [HR], 0.61 [95% CI, 0.40 to 0.92]); however, this result lost statistical significance after adjustment for potential confounders including tumor stage (adjusted HR, 0.74 [95% CI, 0.47 to 1.15]).

Conclusion: This global study provides evidence on the different clinical behavior of breast cancer in young BRCA1 and BRCA2 carriers. Identifying a BRCA PV in healthy individuals was associated with earlier-stage breast cancer diagnosis and lower treatment burden, as well as better unadjusted OS.

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年轻BRCA携带者的乳腺癌临床行为及种系BRCA状态的诊断前意识

目的：根据特异性BRCA基因（BRCA1 v BRCA2），探讨年轻BRCA携带者乳腺癌的临床行为及基因检测时机（诊断前）与预后的关系。方法：这是一项国际、多中心、以医院为基础的回顾性队列研究，纳入了2000年1月至2020年12月全球78个中心的4752名携带BRCA1或BRCA2种系致病/可能致病变异（pv）的患者，这些患者年龄在40岁或以下，被诊断为I-III期浸润性乳腺癌（ClinicalTrials.gov identifier: NCT03673306）。结果：与BRCA2携带者（n = 1,683）相比，BRCA1携带者（n = 3,069）更频繁地出现激素受体阴性（74.4% v 15.5%）和高级别（77.5% v 49.1%）肿瘤。在BRCA1和BRCA2携带者中观察到类似的结果，但随着时间的推移，无病生存事件的模式和风险不同。与诊断时检测BRCA的患者(即诊断前2个月至诊断后6个月；N = 1,671)，诊断前检测(即诊断前2个月的任何时间；n = 411)肿瘤较小（T1: 61.3% v 32.4%），淋巴结累及较少（N0: 65.9% v 50.8%），化疗较少（84.4% v 92.9%），腋窝清扫（37.5% v 47.4%）。诊断前检测的患者总生存期(OS；未调整风险比[HR]， 0.61 [95% CI, 0.40 ~ 0.92])；然而，在校正肿瘤分期等潜在混杂因素后，该结果失去了统计学意义（校正后的HR为0.74 [95% CI, 0.47 ~ 1.15]）。结论：这项全球性的研究为年轻BRCA1和BRCA2携带者乳腺癌的不同临床行为提供了证据。在健康个体中识别BRCA PV与早期乳腺癌诊断和较低的治疗负担以及更好的未调整OS相关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Clinical Oncology 医学-肿瘤学

CiteScore

41.20

自引率

2.20%

发文量

8215

审稿时长

2 months

期刊介绍： The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.