Environmental endocrine disruptors in cardio-oncology: emerging modifiers of cardiovascular vulnerability in patients with cancer.

Abstract

Background: Cardio-oncology has traditionally focused on treatment-related cardiovascular toxicity and conventional cardiovascular risk factors. However, increasing evidence suggests that environmental exposures may contribute to both cancer development and cardiovascular disease through shared biological mechanisms. Endocrine-disrupting chemicals (EDCs) are ubiquitous environmental contaminants capable of interfering with hormonal signaling, metabolic homeostasis, vascular function, and inflammatory pathways. Despite growing evidence linking EDCs to cardiometabolic disorders and hormone-sensitive malignancies, their potential role within the cardio-oncology continuum remains largely unexplored.

Methods: This narrative review summarizes and critically discusses current experimental, translational, and epidemiological evidence regarding the potential contribution of environmental endocrine disruptors to cardiovascular risk and cancer biology. Particular attention is given to molecular pathways relevant to cancer therapy-related cardiovascular toxicity, breast cancer biology, adipose tissue dysfunction, and emerging exposomic determinants of long-term cardiovascular outcomes in patients with cancer.

Main body: Major classes of EDCs, including bisphenols, phthalates, per- and polyfluoroalkyl substances (PFAS), persistent organic pollutants (POPs), parabens, pesticides, and other environmental contaminants, are continuously encountered through food systems, plastics, consumer products, contaminated water, and healthcare materials. These compounds influence multiple biological processes that are central to both oncogenesis and cardiovascular disease, including oxidative stress, mitochondrial dysfunction, endothelial injury, chronic inflammation, metabolic reprogramming, thrombosis, and epigenetic remodeling. In breast cancer, EDCs may modulate subtype-specific signaling pathways involving estrogen receptor activation, HER2 crosstalk, aryl hydrocarbon receptor signaling, and homologous recombination networks. In parallel, growing evidence supports associations between EDC exposure and hypertension, accelerated atherosclerosis, heart failure, metabolic syndrome, and major adverse cardiovascular events. We further discuss the hypothesis that lipophilic EDCs may accumulate within adipose depots and that dysfunctional epicardial adipose tissue could represent a local toxicological niche capable of amplifying cardiovascular vulnerability in cancer survivors, although direct evidence remains unavailable.

Conclusions: EDCs should not yet be considered established cardio-oncology risk factors; however, they represent biologically plausible exposomic modifiers operating at the intersection of cancer, metabolism, and cardiovascular disease. Incorporating environmental exposures into cardio-oncology research may improve understanding of interindividual variability in cardiovascular outcomes and open new avenues for risk stratification, prevention, and survivorship care. Future prospective studies integrating exposure biomarkers, adipose tissue biology, and cardiovascular phenotyping are warranted to define the clinical relevance of EDCs in patients with cancer.