Continuous Trastuzumab Therapy in Breast Cancer Patients With Asymptomatic Left Ventricular Dysfunction

Abstract

Background: Adjuvant trastuzumab is a highly effective targeted treatment that improves survival for patients with HER2-positive breast cancer. However, trastuzumab interruption is recommended for patients who develop treatment-induced cardiotoxicity (i.e., decline in left ventricular ejection fraction [LVEF], with or without symptoms) and can lead to an incomplete course of treatment. We studied the cardiac safety of continuous trastuzumab therapy among patients with asymptomatic declines in LVEF.

Methods: We retrospectively evaluated patients with HER2-positive breast cancer treated with adjuvant trastuzumab at our institution between 2005 and 2010. Treatment-induced cardiotoxicity was defined by an absolute decrease in LVEF of ≥10% to below 55% or an absolute decrease of ≥16%. Logistic regression was used to determine the association between candidate risk factors and treatment-induced cardiotoxicity.

Results: Among 573 patients, 92 (16%) developed treatment-induced cardiotoxicity. Trastuzumab was continued without interruption in 31 of 92 patients with treatment-induced cardiotoxicity—all were asymptomatic with LVEF of ≥50% at cardiotoxicity diagnosis with median LVEF of 53% (range, 50%-63%), and none developed heart failure during follow-up. Risk factors associated with treatment-induced cardiotoxicity included age (p = .011), anthracycline chemotherapy (p = .002), and lower pretrastuzumab LVEF (p < .001).

Conclusion: Among patients who develop asymptomatic treatment-induced cardiotoxicity with LVEF of ≥50%, continuous trastuzumab therapy appears to be safe.

Keywords: Adjuvant chemotherapy; Breast cancer; Cardiotoxicity; Heart failure; Trastuzumab.

Figure 1.

Histograms of patients meeting criteria for treatment-induced cardiotoxicity, with and without trastuzumab interruption. (A, B): Baseline LVEF in the group with trastuzumab interruption (A) and the group without trastuzumab interruption (B). (C, D): Nadir LVEF at time of cardiotoxicity diagnosis in the group with trastuzumab interruption (C) and the group without trastuzumab interruption (D). (E, F): Follow-up LVEF (at least 3 months after cardiotoxicity diagnosis) in the group with trastuzumab interruption (E) and the group without trastuzumab interruption (F). ∗, p < .0001 for baseline LVEF in trastuzumab interruption versus no interruption group; ∗∗, p < .0001 for nadir LVEF in trastuzumab interruption versus no interruption group. Abbreviation: LVEF, left ventricular ejection fraction.