Does trastuzumab-related cardiotoxicity influence long-term outcome in patients with HER-2 positive breast cancer? A prospective study

IntroductionTrastuzumab is a monoclonal antibody directed against the HER-2 receptor that has led, in an adjuvant setting, to higher disease-free (DFS) and overall survival (OS) in HER-2 positive breast cancer (BC) compared with chemotherapy alone. Cardiotoxicity often results in early discontinuation of trastuzumab, which may elevate the risk of cancer recurrence or mortality. Our study aimed to assess how early interruption or early permanent termination of adjuvant trastuzumab treatment influences DFS and OS of patients with HER-2 positive BC.Material and methodsThis is a prospective observation of 253 women (55 ±10 years of age) with HER-2 positive unilateral, non-metastatic BC treated with trastuzumab in an adjuvant setting. To monitor the safety of the treatment echocardiography was performed at baseline and every 3 months up to 12 months after the end of therapy. If cardiotoxicity developed, trastuzumab was stopped early. Overall survival and DFS were assessed.ResultsTrastuzumab-associated cardiac complications resulting in treatment discontinuation developed in 52 (20.55%) patients. Median DFS time was 21.1 months in the group with interruption compared with 25.7 months in the group with full trastuzumab treatment, being significantly shorter (HR = 2.32, 95% CI: 1.15–4.71, p = 0.0106). Two year OS in the interruption and no-interruption groups were 80.8% and 88.5%, respectively, which were not statistically significantly different (p = 0.268). In a multivariate regression analysis the cumulative dose of anthracycline (OR = 1.01, 95% CI: 1.00–1.01, p = 0.002) and LVEF at baseline (OR = 0.83, 95% CI: 0.70–0.99, p = 0.0344) were independent predictors of a cardiotoxic effect.ConclusionsTrastuzumab-related cardiotoxicity resulting in early treatment discontinuation negatively influences DFS, but does not seem to influence OS.