Highlights
Exposure to fine particulate matter (PM2.5) and ozone (O3) is independently associated with significant declines in left ventricular ejection fraction (LVEF) and worsened longitudinal strain in patients undergoing cardiotoxic cancer therapy.
Patients in the highest tertiles of PM2.5 and O3 exposure face more than a two-fold increased risk (AHR 2.03 and 2.15, respectively) of developing clinical cardiac dysfunction compared to those in the lowest exposure groups.
The study identifies specific structural changes, including increased left ventricular mass, suggesting that environmental pollutants act as a ‘second hit’ that accelerates adverse cardiac remodeling during cancer treatment.
Background: The Unseen Risk in Cardio-Oncology
The survival rates for breast cancer have improved dramatically over the last few decades, largely due to the efficacy of anthracyclines and HER2-targeted therapies like trastuzumab. However, these life-saving treatments carry a well-documented risk of cardiotoxicity, often manifesting as a decline in left ventricular function or overt heart failure. While clinical risk factors such as age, hypertension, and baseline cardiac function are routinely monitored, the influence of environmental stressors—specifically air pollution—remains a critical but understudied variable in the cardio-oncology equation.
Air pollution, particularly fine particulate matter (PM2.5) and ozone (O3), is a recognized driver of cardiovascular morbidity and mortality in the general population. The mechanisms, which include systemic inflammation, oxidative stress, and autonomic dysfunction, overlap significantly with the pathways of chemotherapy-induced cardiac damage. This study by Jung and colleagues sought to determine whether ambient air pollution levels exacerbate the structural and functional cardiac changes observed in patients receiving cardiotoxic breast cancer treatments.
Study Design: A Longitudinal Prospective Analysis
This longitudinal prospective cohort study included 580 female patients with breast cancer enrolled across multiple sites of a quaternary healthcare system between 2010 and 2018. The inclusion criteria focused on patients initiating anthracycline-based chemotherapy, trastuzumab, or both. The study employed a rigorous monitoring protocol, collecting a total of 3,642 echocardiograms over a median follow-up period of 3.1 years.
Environmental exposure was estimated using three-year average census tract-level concentrations of four major pollutants: PM2.5, PM10, nitrogen dioxide (NO2), and ozone (O3). The primary outcome was the incidence of cardiac dysfunction, defined as a decline in LVEF of 10% or more from baseline to a final value of less than 50%. Secondary measures included core laboratory-quantified echocardiographic indices such as global longitudinal strain (GLS) and left ventricular (LV) mass index.
Results: Quantifying the Environmental Burden
The study cohort had a median age of 50 years, representing a relatively young population where long-term cardiac health is paramount. Over the follow-up period, 17.1% of participants (98 of 574) met the criteria for clinical cardiac dysfunction. The researchers found that the impact of air pollution was not uniform across all pollutants, with PM2.5 and O3 emerging as the primary drivers of adverse outcomes.
The Impact on Left Ventricular Ejection Fraction
Both PM2.5 and O3 showed a strong longitudinal association with LVEF decline. For every interquartile range (IQR) increase in PM2.5 (1.68 μg/m3), there was a mean LVEF change of -1.3% (95% CI, -1.8% to -0.8%). Similarly, an IQR increase in O3 (2.69 ppb) was associated with a -1.4% change in LVEF (95% CI, -1.8% to -1.0%). These findings suggest that even modest increases in pollutant levels can lead to measurable shifts in cardiac pump function over time.
Adverse Structural Remodeling and Strain
Beyond LVEF, the study utilized more sensitive markers of cardiac health. Global longitudinal strain, which can detect subclinical myocardial injury before LVEF drops, worsened significantly with increased exposure to PM2.5 (-1.0%) and O3 (-1.1%). Furthermore, higher levels of these pollutants were linked to increased LV mass. Specifically, PM2.5 exposure was associated with an LV mass increase of 4.8 g/m2, and O3 with an increase of 3.2 g/m2. This structural remodeling suggests a hypertrophic response to environmental stress, potentially as a compensatory but ultimately maladaptive reaction to therapy-induced injury.
Hazard Ratios and Clinical Significance
The most striking findings were revealed in the hazard models. When comparing patients in the highest tertile of exposure to those in the lowest, the risk of developing clinical cardiac dysfunction was more than doubled. The adjusted hazard ratio (AHR) for PM2.5 was 2.03 (95% CI, 1.17-3.52), and for O3, it was 2.15 (95% CI, 1.23-3.78). Interestingly, PM10 and NO2 did not show statistically significant associations with cardiac dysfunction in this cohort, suggesting that the smaller particle size of PM2.5 and the oxidative potential of O3 may be particularly hazardous to the vulnerable myocardium.
Expert Commentary: Mechanistic Pathways and Clinical Implications
The ‘double-hit’ hypothesis is central to interpreting these results. Anthracyclines cause direct DNA damage and mitochondrial dysfunction in cardiomyocytes, while trastuzumab interferes with the HER2 signaling pathway required for cardiac repair. When these patients are simultaneously exposed to PM2.5, which can penetrate the alveolar-capillary membrane and enter the systemic circulation, they face an additional barrage of proinflammatory cytokines and oxidative stress. Ozone further compounds this by inducing pulmonary inflammation and activating the sympathetic nervous system.
From a clinical perspective, these findings suggest that the environment is a non-traditional but modifiable risk factor. While clinicians cannot easily change a patient’s residence, this data supports the inclusion of environmental history in cardio-oncology assessments. Patients in high-pollution areas might benefit from more frequent echocardiographic monitoring or more aggressive use of cardioprotective medications like ACE inhibitors or beta-blockers.
However, the study is not without limitations. The use of census tract-level data provides a proxy for exposure rather than individual-level monitoring, which may not account for time spent indoors or the use of air filtration systems. Additionally, the cohort was primarily female and focused on breast cancer; whether these findings generalize to other cancers or treatment regimens (such as immunotherapy) remains to be seen.
Conclusion: A Call for Environmental Awareness
The study by Jung et al. provides compelling evidence that PM2.5 and ozone exposure are independent risk factors for cardiac dysfunction in breast cancer patients. As the field of cardio-oncology moves toward personalized risk stratification, environmental factors must be integrated into the clinical framework. Mitigating these risks—through public health policy, patient education on air quality alerts, or the use of high-efficiency indoor air filters—may offer a new avenue for protecting the cardiovascular health of cancer survivors.
References
Jung W, Ko K, Smith AM, et al. Air Pollution and Cardiac Remodeling and Function in Patients With Breast Cancer. JAMA Netw Open. 2026;9(1):e2552323. doi:10.1001/jamanetworkopen.2025.52323.
Curigliano G, Lenihan D, Fradley M, et al. Management of Cardiac Toxicity in Cancer Patients: An ESMO Practice Guideline. Ann Oncol. 2020;31(2):171-190.
