Anticancer drug-related cardiotoxicity from adjuvant goserelin and tamoxifen therapy

The ISACS cardiovascular toxicity 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 the combined Goserelin and Tamoxifen therapy for breast cancer and its impact on left ventricular (LV) disfunction at 1-year follow-up. Inverse probability of treatment weighting (IPTW) analysis of the ISACS registry assigning 70 patients to goserelin (3.6 mg subcutaneously once every 28-days), and tamoxifen (40 mg orally once daily) combined therapy. Controls consisted of 120 patients with no adjuvant combined goserelin and tamoxifen therapy. None of the patients developed distant metastasis. Primary tumor immunohistochemistry of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 was performed in all patients. Primary outcome measures were: low LV function in women as defined by an left ventricular ejection fraction (LVEF)<65% and subclinical LV dysfunction as defined by a 10-percentage point decrease of LVEF. 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 was 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. 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.