Comorbidity Burden and Cumulative Anti-HER2 Exposure Associated with Cardiac Dysfunction in Breast Cancer: A Real-World Cardio-Oncology Cohort

@article{sonaglioni2026comorbidity,
  title = {{Comorbidity Burden and Cumulative Anti-HER2 Exposure Associated with Cardiac Dysfunction in Breast Cancer: A Real-World Cardio-Oncology Cohort}},
  author = {Andrea Sonaglioni and Emanuela Fossile and Maria Adelaide Pessi and Maria Gemelli and Massimo Baravelli and Michele Lombardo and Gian Luigi Nicolosi and Barbara Bassani and Antonino Bruno and Paola Muti},
  journal = {Journal of clinical medicine},
  year = {2026},
  month = oct,
  doi = {10.3390/jcm15197700},
  url = {https://europepmc.org/article/PMC/PMC13665819},
  note = {CC BY},
}

TY  - JOUR
TI  - Comorbidity Burden and Cumulative Anti-HER2 Exposure Associated with Cardiac Dysfunction in Breast Cancer: A Real-World Cardio-Oncology Cohort
AU  - Andrea Sonaglioni
AU  - Emanuela Fossile
AU  - Maria Adelaide Pessi
AU  - Maria Gemelli
AU  - Massimo Baravelli
AU  - Michele Lombardo
AU  - Gian Luigi Nicolosi
AU  - Barbara Bassani
AU  - Antonino Bruno
AU  - Paola Muti
PY  - 2026
DA  - 2026/10/01
JO  - Journal of clinical medicine
DO  - 10.3390/jcm15197700
UR  - https://europepmc.org/article/PMC/PMC13665819
AB  - Background: Cancer-therapy-related cardiac dysfunction (CTRCD) remains an important complication of human epidermal growth factor receptor 2 (HER2)-targeted therapy in patients with breast cancer. Although conventional cardiovascular risk factors and serial cardiac imaging are routinely incorporated into cardio-oncology surveillance, the potential contribution of global comorbidity burden and cumulative anti-HER2 treatment exposure remains incompletely characterized. We investigated the occurrence, clinical course, and factors associated with CTRCD in a large real-world population of patients with breast cancer receiving HER2-targeted therapy. Methods: Adult patients with breast cancer exposed to HER2-targeted therapy and undergoing longitudinal cardio-oncology surveillance at a single tertiary center were retrospectively identified over a 10-year accrual period (January 2014–December 2024). Mean individual follow-up was approximately 2.0 years (range, 0.5–9.0 years). CTRCD was defined according to the harmonized International Cardio-Oncology Society (IC-OS) definitions incorporated into the 2022 ESC Guidelines on cardio-oncology, integrating left ventricular ejection fraction (LVEF), left ventricular global longitudinal strain (LV-GLS), and cardiac biomarkers when available. Baseline comorbidity burden was quantified using the Charlson Comorbidity Index (CCI), while cumulative anti-HER2 exposure was quantified according to the total number of treatment cycles. Factors associated with CTRCD were investigated using univariable and parsimonious multivariable logistic regression. Results: A total of 850 patients with breast cancer receiving anti-HER2 therapy were included. CTRCD occurred in 179 patients (21.1%) and was predominantly mild, whereas clinically overt heart failure occurred in 2.9%. LVEF and LV-GLS deteriorated at nadir and subsequently showed substantial recovery during follow-up. Conventional cardiovascular risk factors, previous anthracycline exposure, tumor grade, baseline LVEF, and baseline LV-GLS were not significantly associated with CTRCD. In multivariable analysis, increasing CCI (adjusted OR 1.35 per one-point increase, 95% CI 1.12–1.63; p = 0.002) and cumulative anti-HER2 exposure (adjusted OR 1.41 per five additional cycles, 95% CI 1.10–1.80; p = 0.006) remained associated with CTRCD after mutual adjustment. Progressively higher observed proportions of CTRCD were found across increasing CCI categories and cumulative anti-HER2 exposure levels. Conclusions: In this large real-world cohort assembled over a 10-year accrual period, CTRCD was relatively frequent but predominantly mild and reversible. Greater global comorbidity burden and cumulative anti-HER2 exposure were associated with a higher occurrence of CTRCD. However, the association with cumulative anti-HER2 exposure should be considered hypothesis-generating rather than causal because of potential time-dependent and reverse-causality bias. Prospective validation is required to determine their potential role in individualized cardiovascular surveillance.
SN  - 2077-0383
ER  -