Anthracyclines-induced cardiotoxicity in patients with early breast cancer carrying germline BRCA1/2 mutation: the BRCAN study

被引:0
|
作者
Cortes-Salgado, Alfonso [1 ]
Jose Serrano, Juan [2 ]
Cordero Pereda, David [3 ]
Menacho, Miriam [4 ]
Manuel Del Rey, Jose [4 ]
del Campo-Albendea, Laura [5 ]
Saavedra, Cristina [1 ]
Chamorro, Jesus [1 ]
Rosero, Diana [1 ]
Sotoca, Pilar [1 ]
Guillen-Ponce, Carmen [1 ]
Guerra, Eva [1 ]
Fernandez-Abad, Maria [1 ]
Lopez-Miranda, Elena [1 ]
Martinez-Janez, Noelia [1 ]
Gion, Maria [1 ]
Teresa Salazar, Maria [1 ]
Agudo-Quilez, Pilar [3 ]
Garrido, Pilar [1 ]
Alonso Salinas, Gonzalo Luis [6 ,7 ,8 ]
机构
[1] Hosp Univ Ramon y Cajal IRYCIS, Dept Med Oncol, Madrid 28034, Spain
[2] Grupo Vithas Madrid, Dept Med Oncol, Madrid 28043, Spain
[3] Hosp Univ Ramon y Cajal IRYCIS, Dept Cardiol, Madrid 28034, Spain
[4] Hosp Univ Ramon y Cajal IRYCIS, Clin Biochem Dept, Madrid 28034, Spain
[5] Hosp Univ Ramon y Cajal IRYCIS, Biostat Unit, CIBERESP, ISCIII, Madrid 28029, Spain
[6] Hosp Univ Navarra, Cardiol Dept, Irunlarrea St 3, Pamplona 31008, Navarra, Spain
[7] IdiSNA, Navarrabiomed, Pamplona 31008, Navarra, Spain
[8] Univ Publ Navarra UPNA, Dept Hlth Sci, Pamplona 31008, Navarra, Spain
来源
ONCOLOGIST | 2024年
关键词
breast cancer; anthracyclines; cardiotoxicity; BRCA1/2; cardio-oncology; FAMILY-MEMBER ST2; ASSOCIATION; GUIDELINES; CARRIERS;
D O I
10.1093/oncolo/oyae299
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: 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. Objective: 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. Methods: 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. Results: 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. Conclusions: 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.
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页数:12
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