2827 - Dual HER2 Blockade Is Associated with Increased Cardiovascular Events In Patients with Breast Cancer Receiving Multimodality Therapy
Presenter(s)
M. Oorloff1, Y. Pan2, O. Peony1, M. Lindsey1, J. P. Nesseler1, K. Silos1, H. Tzou1, E. Kha1, V. Tieu1, G. Ramirez1, G. Gorocica1, J. Steers1, B. Stiehl1, K. Britten3, A. Nikolova4, R. H. Mak5, C. Ramin6, and K. M. Atkins1; 1Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, 2Hematology and Cellular Therapy, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, Los Angeles, CA, 3Department of Medicine, Division of Medical Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, 4Department of Cardiology, Cedars-Sinai Medical Center, Los Angeles, CA, 5Department of Radiation Oncology, Mass General Brigham/Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 6Department of Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA
Purpose/Objective(s): HER2-targeted therapies are associated with cardiovascular side effects, yet the impact of dual HER2 blockade in the setting of multimodality treatment, including radiotherapy (RT), remains incompletely characterized. We evaluated the association between dual HER2 therapy and RT exposure on the risk of major adverse cardiovascular events (MACE) in patients with HER2-positive breast cancer.
Materials/Methods: Retrospective analysis of 579 patients with stage I–III HER2-positive breast cancer treated between 2012–2024 at a single institution with =1 echocardiogram available. The left anterior descending coronary artery (LAD) was segmented using Limbus AI (New York, NY) and dose-volume parameters extracted. Cox proportional hazards models estimated hazard ratios (HRs) for MACE, adjusting for baseline cardiovascular risk and treatment factors. Changes in echocardiographic parameters, including left ventricular ejection fraction (LVEF) and diastolic function, from baseline to one year were evaluated.
Results: The median follow-up was 4.9 years (interquartile range [IQR] 2.8-7.5). At breast cancer diagnosis, the median age was 57 years (IQR, 47–66); 28.8% (167/579) had hypertension, 26.6% (154/579) hyperlipidemia, 8.6% diabetes (50/579), and 6.7% atherosclerotic cardiovascular disease (39/579). Most patients had stage I–II disease (84.8%; 491/579); 55.3% received dual HER2 blockade (320/579), 69.3% RT (401/579), and 4.5% anthracyclines (26/579). Twenty-one MACE (3.6%) occurred after HER2 therapy initiation. Adjusting for age, baseline cardiovascular risk, and left-sided RT, dual HER2 therapy was associated with increased MACE risk (HR 2.90; 95% CI 1.08-7.79; p=0.034). At 10 years, the cumulative incidence of MACE was 9.0% (CI 4.0%-16.5%) with dual therapy vs. 5.2% (CI 1.9%-10.8%) with single HER2 therapy. Among dual HER2–treated patients with RT dose data (n=232), there was a trend toward higher MACE risk with LAD mean dose =3 Gy (HR 5.21, 95% CI 0.51–53.50; p=0.17), though events were limited. No significant changes in echocardiographic parameters were observed (p>0.05).
Conclusion: Although overall MACE incidence was low in this contemporary HER2-positive cohort, dual HER2 blockade was independently associated with increased cardiovascular risk. A signal toward higher risk with greater LAD radiation exposure was observed, though event numbers were limited. Notably, cardiovascular events occurred without significant changes in LVEF, suggesting mechanisms beyond conventional systolic dysfunction monitoring. These findings underscore the importance of cardiovascular risk assessment and surveillance in patients receiving dual HER2 therapy and support further investigation of multimodality cardiovascular risks.