Lambertini Matteo, Blondeaux Eva, Tomasello Loredana M, Agostinetto Elisa, Hamy Anne-Sophie, Kim Hee Jeong, Franzoi Maria Alice, Bernstein-Molho Rinat, Hilbers Florentine, Pogoda Katarzyna, Wildiers Hans, Bajpai Jyoti, Ignatiadis Michail, Moore Halle C F, Partridge Ann H, Phillips Kelly-Anne, Toss Angela, Rousset-Jablonski Christine, Criscitiello Carmen, Renaud Tiphaine, Ferrari Alberta, Paluch-Shimon Shani, Fruscio Robert, Cui Wanda, Wong Stephanie M, Vernieri Claudio, Ruddy Kathryn J, Dieci Maria Vittoria, Matikas Alexios, Rozenblit Mariya, Villarreal-Garza Cynthia, De Marchis Laura, Puglisi Fabio, Rodriguez-Wallberg Kenny A, Duhoux Francois P, Livraghi Luca, Bruzzone Marco, Boni Luca, Balmaña Judith
Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genova, Genoa, Italy.
Medical Oncology Department, U.O.C. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
J Clin Oncol. 2025 May 10;43(14):1706-1719. doi: 10.1200/JCO-24-01334. Epub 2025 Feb 24.
To investigate the clinical behavior of breast cancer in young carriers according to the specific gene () and the association of the timing of genetic testing (before at diagnosis) with prognosis.
This was an international, multicenter, hospital-based, retrospective cohort study that included 4,752 patients harboring germline pathogenic/likely pathogenic variants (PVs) in or , 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).
Compared with carriers (n = 1,683), carriers (n = 3,069) had more frequently hormone receptor-negative (74.4% 15.5%) and high-grade (77.5% 49.1%) tumors. Similar outcomes were observed in and carriers but with a different pattern and risk of disease-free survival events over time. Compared with patients tested for 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% 32.4%), less nodal involvement (N0: 65.9% 50.8%), less frequently received chemotherapy (84.4% 92.9%), and axillary dissection (37.5% 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]).
This global study provides evidence on the different clinical behavior of breast cancer in young and carriers. Identifying a PV in healthy individuals was associated with earlier-stage breast cancer diagnosis and lower treatment burden, as well as better unadjusted OS.
根据特定基因（）研究年轻携带者中乳腺癌的临床行为，以及基因检测时间（诊断前与诊断时）与预后的关联。
这是一项国际多中心基于医院的回顾性队列研究，纳入了4752例在或中携带胚系致病/可能致病变异（PVs）的患者，这些患者于2000年1月至2020年12月期间在全球78个中心被诊断为I - III期浸润性乳腺癌，年龄在40岁及以下（ClinicalTrials.gov标识符：NCT03673306）。
与携带者（n = 1683）相比，携带者（n = 3069）的肿瘤更常为激素受体阴性（74.4%对15.5%）和高级别（77.5%对49.1%）。在和携带者中观察到类似结果，但随着时间推移无病生存事件的模式和风险有所不同。与诊断时检测（即诊断前2个月至诊断后6个月内；n = 1671）的患者相比，诊断前检测（即诊断前任何时间至诊断前2个月；n = 411）的患者肿瘤较小（T1：61.3%对32.4%），淋巴结受累较少（N0：65.9%对50.8%），接受化疗的频率较低（84.4%对92.9%），腋窝清扫术的比例较低（37.5%对47.4%）。诊断前检测的患者总生存期（OS）更好（未调整风险比[HR]，0.61[95%CI，0.40至0.92]）；然而，在对包括肿瘤分期在内的潜在混杂因素进行调整后，该结果失去统计学意义（调整后HR，0.74[95%CI，0.47至1.15]）。
这项全球研究为年轻和携带者中乳腺癌的不同临床行为提供了证据。在健康个体中鉴定出PV与早期乳腺癌诊断、较低的治疗负担以及更好的未调整OS相关。
