Cortés-Salgado Alfonso, Serrano Juan José, Cordero Pereda David, Menacho Miriam, Del Rey José Manuel, Del Campo-Albendea Laura, Saavedra Cristina, Chamorro Jesús, Rosero Diana, Sotoca Pilar, Guillén-Ponce Carmen, Guerra Eva, Fernández-Abad María, López-Miranda Elena, Martínez-Jáñez Noelia, Gion María, Salazar María Teresa, Agudo-Quílez Pilar, Garrido Pilar, Alonso Salinas Gonzalo Luis
Medical Oncology Department, Hospital Universitario Ramón y Cajal (IRYCIS), 28034 Madrid, Spain.
Medical Oncology Department, Grupo Vithas Madrid, 28043 Madrid, Spain.
Oncologist. 2025 Aug 4;30(8). doi: 10.1093/oncolo/oyae299.
BRCA1/2 genes play a critical role in genome stability and DNA repair. In animal models, loss of cardiomyocyte-specific BRCA1/2 is associated with DNA damage, apoptosis, cardiac dysfunction, and mortality following anthracycline exposure. However, whether these preclinical findings translate to humans remains unclear.
Assess the impact of germline BRCA1/2 (gBRCA1/2) status on anthracyclines-induced cardiotoxicity (AIC) in patients with early breast cancer and no prior anti-HER2 therapy.
This single-center retrospective/prospective cohort study focused on early breast cancer patients, treated with anthracycline-based chemotherapy in the neo/adjuvant setting, no prior anti-HER2 therapy, and known gBRCA1/2 status, normal baseline left ventricular ejection fraction (LVEF), and no previous cardiovascular disease. Follow-up assessments involved myocardial dysfunction blood biomarkers (MDBB), transthoracic echocardiography (TTE), and quality of life (QoL) questionnaires. The primary objective was LVEF changes comparing BRCA1/2 mutation carriers (gBRCA1/2m) vs non-carriers (gBRCA1/2wt). Secondary objectives included differences in MDBB and QoL.
A total of 137 patients were included (103 gBRCA1/2wt and 34 gBRCA1/2m). Baseline characteristics were similar between groups. Compared to baseline, LVEF% reduction was -4.7[-12.0, 0.0] vs -9.5[-18.0, -5.0] in gBRCA1/2wt vs gBRCA1/2m, (P = .027). After adjusting for confounders, the difference in reduction in LVEF remained statistically significant at -4.5 [95%CI, -8.6, -0.4; P = .032]. No differences between MDBB (C-reactive protein, hsTnI, NT-proBNP, D-Dimer, ST-2, or Galectine-3) or QoL (MLHFQ and EQ5-D index) were detected.
gBRCA1/2m patients could represent a higher-risk population for AIC. gBRCA1/2 status should be one of the factors to consider in deciding on adjuvant anthracycline necessity. This population could benefit from a cardio-oncology closer follow-up and cardioprotective strategies.
BRCA1/2基因在基因组稳定性和DNA修复中起关键作用。在动物模型中，心肌细胞特异性BRCA1/2缺失与DNA损伤、细胞凋亡、心脏功能障碍以及蒽环类药物暴露后的死亡率相关。然而，这些临床前研究结果是否适用于人类仍不清楚。
评估种系BRCA1/2（gBRCA1/2）状态对早期乳腺癌且未接受过抗HER2治疗患者蒽环类药物诱导的心脏毒性（AIC）的影响。
这项单中心回顾性/前瞻性队列研究聚焦于早期乳腺癌患者，这些患者在新辅助/辅助治疗中接受基于蒽环类药物的化疗，未接受过抗HER2治疗，已知gBRCA1/2状态，基线左心室射血分数（LVEF）正常，且既往无心血管疾病。随访评估包括心肌功能障碍血液生物标志物（MDBB）、经胸超声心动图（TTE）和生活质量（QoL）问卷。主要目标是比较BRCA1/2突变携带者（gBRCA1/2m）与非携带者（gBRCA1/2wt）的LVEF变化。次要目标包括MDBB和QoL的差异。
共纳入137例患者（103例gBRCA1/2wt和34例gBRCA1/2m）。两组间基线特征相似。与基线相比，gBRCA1/2wt组LVEF%降低为-4.7[-12.0, 0.0]，gBRCA1/2m组为-9.5[-18.0, -5.0]，（P = 0.027）。在调整混杂因素后，LVEF降低的差异在-4.5[95%CI, -8.6, -0.4；P = 0.032]时仍具有统计学意义。未检测到MDBB（C反应蛋白、高敏肌钙蛋白I、N末端脑钠肽前体、D-二聚体、ST-2或半乳凝素-3）或QoL（MLHFQ和EQ5-D指数）之间的差异。
gBRCA1/2m患者可能是AIC的高危人群。gBRCA1/2状态应是决定辅助蒽环类药物必要性时考虑的因素之一。这一人群可能受益于心肿瘤学的密切随访和心脏保护策略。
