Anticancer-Drug-Related Cardiotoxicity from Adjuvant Goserelin and Tamoxifen Therapy

Background: Breast cancer is a prevalent malignancy with rising incidence globally. Advances in endocrine therapy have improved outcomes for premenopausal women with hormone receptor-positive breast cancer. However, these treatments may induce menopause-like states, potentially elevating cardiovascular risks, including left ventricular (LV) dysfunction. This study aims to evaluate the impact of one year of adjuvant endocrine therapy with goserelin and tamoxifen on LV function in premenopausal breast cancer patients. Methods: The ISACS cardiovascular toxicity (NCT01218776) is a pilot multicenter registry of breast cancer patients referred to hospitals for routine surveillance, suspected, or confirmed anticancer-drug-related cardiotoxicity (ADRC). Patients may be enrolled retrospectively (1 year) and prospectively. The pilot phase focused on the available data on combined goserelin and tamoxifen therapy for breast cancer and its impact on LV disfunction at 1-year follow-up. Inverse probability of treatment weighting (IPTW) analysis of the ISACS registry was performed assigning 70 patients to combined endocrine therapy (goserelin and tamoxifen). Controls consisted of 120 patients with no adjuvant combined goserelin and tamoxifen therapy. None of the patients developed distant metastasis. Primary outcome measures were as follows: low LV function in women as defined by a left ventricular ejection fraction (LVEF) < 65% and subclinical LV dysfunction as defined by a 10-percentage point decrease in LVEF. Results: In the overall population, combined goserelin and tamoxifen therapy did not affect the mean LV function compared with controls at 3-, 6-, and 12-month follow-up (65.7 +/- 2.7% versus 65.3 +/- 2.1%, p value = 0.27; 65.5 +/- 2.9% versus 65.1 +/- 2.5%, p value = 0.34; 65.0 +/- 3.2% versus 64.6 +/- 3.1%, p value = 0.29, respectively). The mean LVEF reduction in patients who did or did not receive combination therapy for 12 months was small and approximately similar (1.03 +/- 2.5% versus 1.16 +/- 2.9%, p value = 0.73). Using IPTW analyses, there were no significant associations between combined therapy and low LV function (risk ratio [RR]: 1.75; 95% CI: 0.71-4.31) or subclinical LV dysfunction (RR: 1.50; 95% CI: 0.35-6.53) compared with controls. Conclusions: One year of endocrine therapy with goserelin and tamoxifen does not cause ADRC in patients with invasive breast cancer. Findings are independent of the severity of the disease. Results may not be definitive without replication in studies with larger sample size.