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. 2025 Aug 4;30(8):oyae299.
doi: 10.1093/oncolo/oyae299.

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

Alfonso Cortés-Salgado  1 , Juan José Serrano  2 , David Cordero Pereda  3 , Miriam Menacho  4 , José Manuel Del Rey  4 , Laura Del Campo-Albendea  5 , Cristina Saavedra  1 , Jesús Chamorro  1 , Diana Rosero  1 , Pilar Sotoca  1 , Carmen Guillén-Ponce  1 , Eva Guerra  1 , María Fernández-Abad  1 , Elena López-Miranda  1 , Noelia Martínez-Jáñez  1 , María Gion  1 , María Teresa Salazar  1 , Pilar Agudo-Quílez  3 , Pilar Garrido  1 , Gonzalo Luis Alonso Salinas  6   7   8
Affiliations

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

Alfonso Cortés-Salgado et al. Oncologist. .

Abstract

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.

Keywords: BRCA1/2; anthracyclines; breast cancer; cardio-oncology; cardiotoxicity.

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Conflict of interest statement

Alfonso Cortés-Salgado reported consulting/advisory relationship with GSK, AstraZeneca, Daiichi Sankyo, and Pfizer; research funding from Pfizer; expert testimony for GSK, AstraZeneca, Accord Healthcare, and Pfizer; and travel expenses from Pfizer and GSK. Carmen Guillén-Ponce reported research funding (institutional): QED Therapeutics, AstraZeneca, Boston, Erytech, IPSEN, Panbela Therapeutics, Oncosil Medical; expert testimony: Boston; travel, accommodations, expenses: AstraZeneca, Roche, GE Healthcare. Eva Guerra has received advisory/consultancy honorarium from AstraZeneca-MSD, Clovis Oncology, GSK-Tesaro, PharmaMar, and Roche; has received speaker bureau/expert testimony honorarium from AstraZeneca-MSD, PharmaMar, Roche, GSK-Tesaro, Clovis, and Eisai; and has received travel/accommodation/expenses from Roche, GSK-Tesaro, and Baxter. María Fernández-Abad reported honoraria from Lilly, Novartis, Eisai, Ferrer, Persan, AstraZeneca/Daiichi; and Scientific Advisory Board for Lilly and Seagen. Maria Gion has received honoraria from Novartis, Gilead, AstraZeneca, and Pfizer; travel grants and accommodation from Roche, Pfizer, and AstraZeneca; and serves on advisory board for Gilead and AstraZeneca. Pilar Garrido reported consultancy/honoraria from Abbvie, Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Daiichi Sankyo, GlaxoSmithKline, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, and Takeda; direct funding from Medscape and Touch Medical; institutional research funding from Amgen, AstraZeneca, Blueprint, BMS, Boehringer Ingelheim, Daiichi Sankyo, GlaxoSmithKline, Janssen, IO Biotech, Lilly, MSD, Roche, and Takeda. The other authors indicated no financial relationships.

Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
(A) Left ventricular ejection fraction before and after anthracyclines. (B) Average reduction in left ventricular ejection fraction after anthracyclines.
Figure 2.
Figure 2.
(A) Traditional myocardial dysfunction blood biomarkers. (B) Novel myocardial dysfunction blood biomarkers.
Figure 3.
Figure 3.
Heart-related quality of life questionnaires.
See this image and copyright information in PMC

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