Sex-Specific Cardiovascular Risks of Cancer and Its Therapies
Open accessAbstract
In both cardiovascular disease and cancer, there are established sex-based differences in prevalence and outcomes. Males and females may also differ in terms of risk of cardiotoxicity following cancer therapy, including heart failure, cardiomyopathy, atherosclerosis, thromboembolism, arrhythmias, and myocarditis. Here, we describe sex-based differences in the epidemiology and pathophysiology of cardiotoxicity associated with anthracyclines, hematopoietic stem cell transplant (HCT), hormone therapy and immune therapy. Relative to males, the risk of anthracycline-induced cardiotoxicity is higher in prepubertal females, lower in premenopausal females, and similar in postmenopausal females. For autologous hematopoietic cell transplant, several studies suggest an increased risk of late heart failure in female lymphoma patients, but sex-based differences have not been shown for allogeneic hematopoietic cell transplant. Hormone therapies including GnRH (gonadotropin-releasing hormone) modulators, androgen receptor antagonists, selective estrogen receptor modulators, and aromatase inhibitors are associated with cardiotoxicity, including arrhythmia and venous thromboembolism. However, sex-based differences have not yet been elucidated. Evaluation of sex differences in cardiotoxicity related to immune therapy is limited, in part, due to low participation of females in relevant clinical trials. However, some studies suggest that females are at increased risk of immune checkpoint inhibitor myocarditis, although this has not been consistently demonstrated. For each of the aforementioned cancer therapies, we consider sex-based differences according to cardiotoxicity management. We identify knowledge gaps to guide future mechanistic and prospective clinical studies. Furthering our understanding of sex-based differences in cancer therapy cardiotoxicity can advance the development of targeted preventive and therapeutic cardioprotective strategies.
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Preclinical and clinical studies demonstrate that females exhibit a higher frequency and severity of ICI myocarditis, primarily driven by α-MyHC-specific autoreactive T cells.
“This hypothesis is further supported by preclinical and clinical studies demonstrating that females exhibit a higher frequency and severity of ICI myocarditis, primarily driven by α -MyHC-specific autoreactive T cells. 51,273,274”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [274]
The Immunotherapy section reports higher myocarditis-related mortality in female mice in one preclinical model, and its epidemiology subsection cites one clinical study suggesting higher incidence in women. But it says the clinical evidence is mixed and insufficient to establish a sex predilection; it does not identify α-MyHC-specific autoreactive T cells as the primary driver. Page numbers are unavailable in our copy. (LLM, conf=0.88)
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- Authors
- Wilcox, N. S., Rotz, S. J., Mullen, M., Song, E. J., Ky Hamilton, B., Moslehi, J., Armenian, S. H., Wu, J. C., Rhee, J.-W., & Ky, B.
- Affiliations
- University of Pennsylvania (US)
- Cleveland Clinic (US)
- Stanford Cardiovascular Institute (US)
- University of California, San Francisco (US)
- Department of Hematology and Oncology, Taussig Cancer Institute (S.J.R., B.K.H.), Cleveland Clinic Foundation, OH.
- City Of Hope National Medical Center (US)
- Abramson Cancer Center (US)
- ORCID
- Venue
- Circulation Research
- Published
- 2022-02-18
- Volume
- 130
- Issue
- 4
- Pages
- 632-651
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- PMC
- PMC8915444
- OpenAlex
- W4212924228
- Cited by
- 86
- References
- 162
- Citations by year
- 2026: 18 · 2025: 25 · 2024: 21 · 2023: 12 · 2022: 10
- FWCI
- 11.84
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (KL2TR002547)
- National Heart, Lung, and Blood Institute (R21HL157886, R21HL141802, R01HL148272, R01HL123968, R01HL150069, R21HL152148, R01HL152707, K08HL148540, R01HL141466, R21HL150723, R34HL146927, R01HL156021, R01HL141851, R01HL150693, R01HL155990)
- National Cancer Institute (R01CA196854)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Chemotherapy-induced cardiotoxicity and mitigation
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac tumors and thrombi
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- sex differences, cardiotoxicity, cancer therapy, anthracycline cardiotoxicity, hematopoietic stem cell transplantation, hormone therapy, immune checkpoint inhibitors, myocarditis, heart failure, cardiac arrhythmias, venous thromboembolism, aromatase inhibitors, selective estrogen receptor modulators, androgen receptor antagonists, lymphoma, cardioprotection
- MeSH terms
- Heart Disease Risk Factors, Antineoplastic Agents, Cardiovascular Diseases, Female, Humans, Immunotherapy, Male, Neoplasms, Sex Characteristics, Hematopoietic Stem Cell Transplantation, Anthracyclines, Hormone Replacement Therapy, Cardiotoxicity
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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