Trastuzumab-induced cardiotoxicity in breast cancer survivors was associated with lower long-term LVEF (56.9% vs 62.4%; P<0.001) and peak oxygen consumption (22.9 vs 27.0 mL/kg/min; P=0.03).
Cross-Sectional (n=57)
No
Is a history of trastuzumab-induced cardiotoxicity associated with long-term cardiopulmonary dysfunction in survivors of ERBB2-positive breast cancer?
Trastuzumab-induced cardiotoxicity in breast cancer survivors is associated with long-term subclinical cardiopulmonary impairment, including reduced peak VO2 and global longitudinal strain, even years after treatment completion.
Absolute Event Rate: 56.9% vs 62.4%
p-value: p=<0.001
Importance: Trastuzumab improves outcomes in patients with ERBB2-positive (formerly HER2) breast cancer but is associated with treatment-induced cardiotoxicity, most commonly manifest by an asymptomatic decline in left ventricular ejection fraction (LVEF). Little is known to date regarding the long-term effects of treatment-induced cardiotoxicity on cardiopulmonary function in patients who survive trastuzumab-treated breast cancer. Objective: To determine whether treatment-induced cardiotoxicity recovers or is associated with long-term cardiopulmonary dysfunction in survivors of ERBB2-positive breast cancer. Design, Setting, and Participants: This cross-sectional case-control study enrolled patients with nonmetastatic ERBB2-positive breast cancer after completion of trastuzumab-based therapy (median, 7.0 interquartile range (IQR), 6.2-8.7 years after therapy) who met 1 of 2 criteria: (1) cardiotoxicity (TOX group) developed during trastuzumab treatment (ie, asymptomatic decrease of LVEF≥10% from baseline to <55% n = 22) or (2) no evidence of cardiotoxicity during trastuzumab treatment (NOTOX group n = 20). Patients were treated at the Memorial Sloan Kettering Cancer Center. Fifteen healthy control participants (HC group) were also enrolled for comparison purposes. All groups were frequency matched by age strata (<55, 55-64, and ≥65 years). Data were collected from September 9, 2016, to August 10, 2018, and analyzed from November 20, 2018, to August 12, 2019. Main Outcomes and Measures: Speckle-tracking echocardiography and maximal cardiopulmonary exercise testing were performed to measure indices of left ventricular function (including LVEF and global longitudinal strain GLS) and peak oxygen consumption (peak VO2). Results: A total of 57 participants (median age, 60.8 IQR, 52.7-65.7 years) were included in the analysis. Overall, 38 of 42 patients with breast cancer (90%) were treated with anthracyclines before trastuzumab. Resting mean (SD) LVEF was significantly lower in the TOX group (56.9% 5.2%) compared with the NOTOX (62.4% 4.0%) and HC (65.3% 2.9%) groups; similar results were found for GLS (TOX group, -17.8% 2.2%; NOTOX group, -19.8% 2.2%; HC group, -21.3% 1.8%) (P < .001). Mean peak VO2 in the TOX group (22.9 4.4 mL/kg/min) was 15% lower compared with the NOTOX group (27.0 5.3 mL/kg/min; P = .03) and 25% lower compared with the HC group (30.5 3.4 mL/ kg/min; P < .001). In patients with breast cancer, GLS was significantly associated with peak VO2 (β coefficient, -0.75; 95% CI, -1.32 to -0.18). Conclusions and Relevance: Treatment-induced cardiotoxicity appears to be associated with long-term marked impairment of cardiopulmonary function and may contribute to increased risk of late-occurring cardiovascular disease in survivors of ERBB2-positive breast cancer.
Yu et al. (Wed,) conducted a cross-sectional in ERBB2-positive breast cancer (n=57). Treatment-induced cardiotoxicity vs. No cardiotoxicity and healthy controls was evaluated on Left ventricular ejection fraction (LVEF) (p=<0.001). Trastuzumab-induced cardiotoxicity in breast cancer survivors was associated with lower long-term LVEF (56.9% vs 62.4%; P<0.001) and peak oxygen consumption (22.9 vs 27.0 mL/kg/min; P=0.03).