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Cardiopulmonary Consequences of Treatment-Induced Cardiotoxicity in Breast Cancer Survivors
Study Questions:
Is cardiotoxicity during therapy with trastuzumab in ERBB2-positive breast cancer patients associated with long-term changes in cardiopulmonary function?
Methods:
The authors used a cross-sectional case-control study design of 42 women with nonmetastatic ERBB2-positive breast cancer who completed therapy with trastuzumab, stratified into two groups: 22 patients with a history of cardiotoxicity (TOX) during treatment (defined as a 10% decrease in left ventricular ejection fraction [LVEF] to <55%) and 20 patients without history of cardiotoxicity (NOTOX) (defined as a maximum decline of LVEF of 5%). Patients with heart failure during treatment were excluded. Fifteen healthy women matched by age strata to the breast cancer cohort were recruited as controls (HC). All participants underwent echocardiography and cardiopulmonary testing as part of the study protocol. The median time from completion of trastuzumab to study testing was 7.0 years (interquartile range [IQR], 6.2-8.7).
Results:
The median age of study participants was 60.8 years (IQR, 52.7-65.7), and prevalence of cardiovascular risk factors was similar across groups. 38 of 42 patients were previously treated with anthracyclines. Mean LVEF pre-trastuzumab was normal and similar between both groups. At the time of the study, the mean LVEF was lower in the TOX group (56.9% [5.2%]) compared with the NOTOX (62.4% [4.0%]) and HC groups (65.3% [2.9%]). Only three patients in the TOX group had an LVEF <53%. Similarly, the mean global longitudinal strain (GLS) was worse in the TOX group (−17.8% [2.2%]) compared with the NOTOX group (−19.8% [2.2%]) and the HC group (−21.3% [1.8%]). Mean peak oxygen consumption (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) and 25% lower compared with the HC group (30.5 [3.4] ml/kg/min). The TOX group had a significantly lower mean post-exercise LVEF compared with the HC group (65.6% [7.7%] vs. 75.6% [5.1%]). Resting GLS correlated with peak VO2 (β −0.63 [−1.35 to 0.08]).
Conclusions:
Patients with breast cancer and a history of anthracycline use with asymptomatic decline in LVEF during trastuzumab therapy had long-term impairment in cardiac function and peak VO2.
Perspective:
This small study of breast cancer patients with and without a history of asymptomatic LVEF decline highlights the potential long-term impact of cardiotoxic therapies on cardiopulmonary function. The correlation noted between GLS and peak VO2 suggests that a subclinical decrease in cardiac function may underlie the impaired exercise capacity of breast cancer survivors. The authors imply that the decrease in peak VO2 may be a surrogate for worse long-term hard outcomes in this patient population, although that remains to be shown. Findings need to be replicated in a larger sample size and more rigorous study design, as the study was cross-sectional, with a very small sample size and no report on blinding of research staff to the group allocation.
Clinical Topics: Cardio-Oncology, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Prevention, Acute Heart Failure, Echocardiography/Ultrasound
Keywords: Anthracyclines, Breast Neoplasms, Cardiotoxicity, Echocardiography, Exercise Tolerance, Heart Failure, Oxygen Consumption, Risk Factors, Secondary Prevention, Stroke Volume, Ventricular Function, Left
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