Management strategies and clinical outcomes in breast cancer patients who develop left ventricular dysfunction during trastuzumab therapy

Ren Jie Robert Yao,Christine Simmons,Margot K Davis,Jordan Gibson

doi:10.1186/s40959-021-00099-7

Abstract

BackgroundTrastuzumab reduces risk of breast cancer recurrence but carries risk of cardiotoxicity that may be reversible upon treatment cessation and institution of left ventricular (LV) enhancement therapies (LVETx). We assessed management patterns of trastuzumab-induced cardiotoxicity (TIC) in a contemporary real-world setting.MethodsWe reviewed charts of all breast cancer patients who received adjuvant trastuzumab in British Columbia between January 2010 and December 2013, spanning the opening of a cardio-oncology clinic. LV dysfunction (LVD) was classified as minimal (LVEF nadir 45–49%), mild (40–44%) or moderate-severe (< 40%). Charts were reviewed for baseline characteristics, management strategies, and outcomes. Multivariable analysis was performed to identify patient characteristics associated with trastuzumab completion and cardiology referral.ResultsOf 967 patients receiving trastuzumab, 171 (17.7%) developed LVD, including 114 patients (11.8%) with LVEF declines of ≥10 to < 50%. Proportions of patients receiving cardiology referrals and LVETx increased and wait times to consultation decreased after a dedicated cardio-oncology clinic opened. LVETx was used more frequently in patients with moderate-severe LVD compared to minimal or mild LVD. Factors associated with completion of trastuzumab included mastectomy (OR 5.1, 95% CI 1.1–23.0) and proximity to quaternary care centre (OR 7.7, 95% CI 2.2–26.2). Moderate-severe LVD was associated with a lower probability of completing trastuzumab (OR 0.07 vs. minimal LVD, 95% CI 0.01–0.74). Factors associated with cardiology referral included heart failure symptoms (OR 8.0, 95% CI 1.5–42.9), proximity to quaternary care centre (OR 6.8, 95% CI 1.3–34.2), later year of cancer diagnosis (OR 2.4 per year, 95% CI 1.4–4.3), node-positive disease (OR 0.18, 95% CI 0.06–0.56), mastectomy (OR 0.05, 95% CI 0.01–0.52), and minimal LVD (OR 0.14, 95% CI 0.05–0.46). LVEF recovered to > 50% in 90.7% of patients.ConclusionsManagement strategies in patients with TIC are associated with cancer characteristics and severity of cardiotoxicity. Access to dedicated cardio-oncology clinics may facilitate optimal care of this complex patient population.

Highlights

Trastuzumab is a recombinant humanized monoclonal antibody directed against the human epidermal growth factor receptor-2 (HER2) receptor, which is overexpressed in 20–30% of breast cancers and associated with aggressive tumour activity [1]
Patient characteristics We identified 967 patients with HER2+ breast cancer treated with adjuvant trastuzumab during the study period
We observed an increased cardiology referral rate, a decrease in wait time to cardiology assessment, and increased Left ventricular enhancement therapy (LVETx) use over the study period, which spanned the time of establishment of a local dedicated cardio-oncology program

Summary

Introduction

Trastuzumab is a recombinant humanized monoclonal antibody directed against the human epidermal growth factor receptor-2 (HER2) receptor, which is overexpressed in 20–30% of breast cancers and associated with aggressive tumour activity [1]. Trastuzumab induces cell death through antibody-dependent cellular cytotoxicity in cells overexpressing HER2, and has revolutionized the care of breast cancer patients by demonstrated marked survival benefit in adjuvant and metastatic settings [2, 3]. In landmark trials of trastuzumab in combination with chemotherapy in operable breast cancer, this agent was associated with a 50% reduction in risk of recurrence and a 33% reduction in the risk of death [4]. The landmark HERA trial of adjuvant trastuzumab therapy reported a 7.1% incidence of LVD, defined as a decrease in LVEF of 10% or more to an LVEF < 50, 1.7% incidence of symptomatic heart failure, and 0.5% incidence of severe heart failure, defined as New York Heart Association (NYHA) class III-IV symptoms [2]. Trastuzumab reduces risk of breast cancer recurrence but carries risk of cardiotoxicity that may be reversible upon treatment cessation and institution of left ventricular (LV) enhancement therapies (LVETx). We assessed management patterns of trastuzumab-induced cardiotoxicity (TIC) in a contemporary real-world setting

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Results

Discussion

Conclusion