Sex Differences in Cancer and Cardiotoxicity: Mechanisms, Outcomes, and Clinical Implications Across Solid and Hematological Malignancies

Sex differences influence cancer incidence, treatment response, and susceptibility to cardiovascular toxicity. Males exhibit higher rates and poorer outcomes in most non-sex-specific cancers, while females more frequently experience treatment-related adverse events, including cancer therapy-related cardiac dysfunction. Biological factors such as hormonal status, genetic polymorphisms, immune responses, and pharmacokinetics contribute to these disparities. In cardio-oncology, women—particularly premenopausal or with specific genotypes—may be at increased risk for cardiotoxicity after treatment with anthracyclines, immune checkpoint inhibitors or radiotherapy. Clonal hematopoiesis and certain germline genetic variants such as single nucleotide polymorphisms (e.g., RARG rs2229774, HAS3 rs2232228) are emerging as potential sex-informed biomarkers for predicting cardiotoxicity risk. Despite growing evidence, sex remains insufficiently integrated into clinical trials and guideline development in cardio-oncology. This review highlights the importance of sex-specific surveillance, prevention, and multi-omic risk stratification to advance precision cardio-oncology and support better outcomes for patients across the cancer care continuum.

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Publication Details

Journal
Cancers
Published
2026-05-22
DOI
https://doi.org/10.3390/cancers18111677
Primary Topic
Chemotherapy-induced cardiotoxicity and mitigation
Type
article
Field-Weighted Citation Impact
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article

Sex Differences in Cancer and Cardiotoxicity: Mechanisms, Outcomes, and Clinical Implications Across Solid and Hematological Malignancies

Alexandra Drakaki, Tochi Okwuosa, J J Fuster, M A M A S Mamas et al.
Cancers
Chemotherapy-induced cardiotoxicity and mitigation
article

Sex Differences in Cancer and Cardiotoxicity: Mechanisms, Outcomes, and Clinical Implications Across Solid and Hematological Malignancies

Alexandra Drakaki, Tochi Okwuosa, J J Fuster, M A M A S Mamas, Daniela Cardinale, Susan Dent, P Van Der Meer, Lydia Scarfo, Jutta Bergler-Klein, Giuseppe Boriani, Marianne C. Aznar, Eric H. Yang, Kalliopi Keramida, Teresa Lopez-Fernandez
article en

Abstract

Sex differences influence cancer incidence, treatment response, and susceptibility to cardiovascular toxicity. Males exhibit higher rates and poorer outcomes in most non-sex-specific cancers, while females more frequently experience treatment-related adverse events, including cancer therapy-related cardiac dysfunction. Biological factors such as hormonal status, genetic polymorphisms, immune responses, and pharmacokinetics contribute to these disparities. In cardio-oncology, women—particularly premenopausal or with specific genotypes—may be at increased risk for cardiotoxicity after treatment with anthracyclines, immune checkpoint inhibitors or radiotherapy. Clonal hematopoiesis and certain germline genetic variants such as single nucleotide polymorphisms (e.g., RARG rs2229774, HAS3 rs2232228) are emerging as potential sex-informed biomarkers for predicting cardiotoxicity risk. Despite growing evidence, sex remains insufficiently integrated into clinical trials and guideline development in cardio-oncology. This review highlights the importance of sex-specific surveillance, prevention, and multi-omic risk stratification to advance precision cardio-oncology and support better outcomes for patients across the cancer care continuum.

CancersVol. 18(11)
University of Modena and Reggio Emilia (IT), Rush University Medical Center (US), University Medical Center Groningen (NL), Vita-Salute San Raffaele University (IT), University of California, Los Angeles (US), National and Kapodistrian University of Athens (GR), Spanish National Centre for Cardiovascular Research (ES), University of Manchester (GB), Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (ES), Hospital La Paz Institute for Health Research (ES), Hospital Universitario Quirónsalud Madrid (ES), Hospital Quirónsalud Barcelona (ES), Centro de Investigación Biomédica en Red (ES), St Savas Hospital (GR), IRCCS Ospedale San Raffaele (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), University of Rochester (US), Keele University (GB), European Institute of Oncology (IT), Medical University of Vienna (AT)
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Openalex Percentile: Top 6%
Chemotherapy-induced cardiotoxicity and mitigation
DOIOpen Access PDFOpenAlex
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