Retrospective evaluation of cardiotoxicity rates in patients diagnosed with breast carcinoma receiving anti-HER2 treatment

Objective: Breast cancer is the most common malignancy in women worldwide, and its incidence is steadily increasing. Breast cancer has also become a significant cause of mortality. Anti-HER2 (Human Epidermal Growth Factor Receptor 2) inhibitors are increasingly being utilized in the treatment of breast cancer. This thesis aims to determine the rates of cardiotoxicity associated with anti-HER2 therapies used in breast cancer treatment and identify the factors influencing its development. Methods: The study included a total of 257 patients aged 18 and older who presented with a diagnosis of breast cancer to the Medical Oncology Clinic of Dokuz Eylül University Faculty of Medicine (DEÜ) between 2017 and 2022. Diagnosis, treatment, and follow-up were conducted at the DEÜ Faculty of Medicine Medical Oncology Clinic. Patients with incomplete data and those not receiving anti-HER2 treatment were excluded from the study. The demographic, clinical, laboratory, and echocardiographic data of the patients were retrospectively analyzed. Patients with a decrease in ejection fraction (EF) and the development of congestive heart failure (CHF) during follow-up were identified. The demographic, clinical, and treatment-related characteristics of these patients were examined for their impact on EF decline and the development of CHF during follow-up in patients receiving anti-HER2 therapy. Chi-square and Fisher's exact tests were used for group comparisons. Multivariate regression analysis was performed with parameters with p<0.1 in the univariate regression analysis to determine risk factors for EF decline and CHF development. A p-value of less than 0.05 was considered statistically significant in all tests. Results: When comparing breast cancer patients at all stages, the baseline echocardiography (EKO) median level was 60.0 (45.0-68.0). The rate of patients with decreased ejection fraction (EF) was 12.1%, and the mean percentage decrease in EF was 11.2±6.2%. The time to EF decline after treatment was calculated as 11.2±6.1 months. The average age at diagnosis for patients with EF decline was 58.7±14.6, while for those without EF decline, it was 53.3±11.8 years, with a borderline statistical significance between the groups (p=0.051). There were no statistically significant differences between the groups in terms of gender distribution, menopausal status at the time of diagnosis, stage distribution at the time of diagnosis, and Eastern Cooperative Oncology Group (ECOG) score distribution. The rates of coronary artery disease (CAD) and hypertension (HT) were statistically significantly higher in the group with EF decline compared to the group without EF decline (p=0.003 and p=0.026, respectively). Among the patients, 29.6% received dual anti-HER2 therapy, and 76.3% received anthracycline treatment. The group without EF decline had a higher percentage of patients receiving anthracycline treatment. There was no statistical difference when comparing patients receiving dual anti-HER2 therapy to those receiving single anti-HER2 therapy.In patients with identified EF decline, it was found that treatment was discontinued in 35.5% of cases, and 73.3% showed improvement in EF during follow-up. The rate of restarting treatment in patients whose treatment was discontinued was 45.5%. Medical treatment was administered to 51.6% of patients with EF decline, with 68.8% receiving angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) and 31.3% receiving beta-blockers. Congestive heart failure (CHF) developed in 35.5% of patients with EF decline, and among those, 45.5% were in stage 1 and 54.5% were in stage Conclusion: In our study, it was determined that 12.1% of patients diagnosed with breast cancer and receiving anti-HER2 treatment experienced a decrease in EF percentage, and 4.2% developed congestive heart failure (CHF) as a result of this treatment. Advanced age, hypertension (HT), and not receiving anthracycline were identified as dependent risk factors for the development of cardiac dysfunction, with the presence of CAD being an independent risk factor. The reversibility of this cardiotoxicity with treatment cessation and timely initiation of medical interventions underscores the importance of recognizing this condition, which primarily occurs in patients. Therefore, regular cardiac assessments should be performed periodically in patients diagnosed with breast cancer receiving anti-HER2 treatment. Patients should be monitored for EF decline or clinical signs of heart failure during follow-up based on echocardiographic evaluations. Keywords: Breast cancer, anti-her2 therapy, cardiotoxicity, congestive heart failur