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

Alfonso Cortés-Salgado1, Juan José Serrano2, David Cordero Pereda3

  • 1Medical Oncology Department, Hospital Universitario Ramón y Cajal (IRYCIS), 28034 Madrid, Spain.

The Oncologist
|November 19, 2024
PubMed
Abstract

Insights

Patients with germline BRCA1/2 mutations (gBRCA1/2m) experienced greater reductions in left ventricular ejection fraction (LVEF) after anthracycline chemotherapy compared to non-carriers. This suggests gBRCA1/2m patients may need closer cardiac monitoring during cancer treatment.

Area of Science:

  • Cardio-oncology
  • Genetics
  • Oncology

Background:

  • BRCA1/2 genes are crucial for DNA repair and genome stability.
  • Loss of cardiomyocyte BRCA1/2 in animal models leads to cardiac damage and mortality after anthracyclines.
  • Human relevance of BRCA1/2's role in anthracycline-induced cardiotoxicity (AIC) is not well-established.

Purpose of the Study:

  • To investigate the impact of germline BRCA1/2 (gBRCA1/2) status on anthracycline-induced cardiotoxicity (AIC).
  • To compare left ventricular ejection fraction (LVEF) changes in early breast cancer patients with and without gBRCA1/2 mutations receiving anthracycline chemotherapy.
  • To assess differences in myocardial dysfunction blood biomarkers (MDBB) and quality of life (QoL) between groups.

Main Methods:

  • Retrospective/prospective cohort study of early breast cancer patients treated with anthracyclines.
  • Exclusion of patients with prior anti-HER2 therapy, pre-existing cardiovascular disease, or abnormal baseline LVEF.
  • Assessment of LVEF via echocardiography, MDBB, and QoL questionnaires, comparing gBRCA1/2 mutation carriers (gBRCA1/2m) with non-carriers (gBRCA1/2wt).

Main Results:

  • 137 patients included: 34 gBRCA1/2m and 103 gBRCA1/2wt.
  • A statistically significant greater reduction in LVEF was observed in gBRCA1/2m patients (-9.5%) compared to gBRCA1/2wt patients (-4.7%) (P=0.027).
  • Adjusted analysis confirmed a significant difference in LVEF reduction (-4.5%, P=0.032); no significant differences in MDBB or QoL were found.

Conclusions:

  • Germline BRCA1/2 mutation carriers represent a population at higher risk for AIC.
  • gBRCA1/2 status should be considered when determining the necessity of adjuvant anthracyclines.
  • This patient group may benefit from enhanced cardio-oncology surveillance and cardioprotective interventions.
Keywords:
BRCA1/2anthracyclinesbreast cancercardio-oncologycardiotoxicity

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