Clinical, Echocardiographic, and Biomarker Associations With Impaired Cardiorespiratory Fitness Early After HER2-Targeted Breast Cancer Therapy.

Background: Cardiorespiratory fitness (CRF) is reduced in cancer survivors and predicts cardiovascular disease (CVD)-related and all-cause mortality. However, routine measurement of CRF is not always feasible.
Objectives: The purpose of this study was to identify clinical, cardiac biomarker, and imaging measures associated with reduced peak oxygen consumption (VO ₂ peak) (measure of CRF) early post-breast cancer therapy to help inform CVD risk.
Methods: Consecutive women with early-stage HER2+ breast cancer receiving anthracyclines and trastuzumab were recruited prospectively. Within 6 ± 2 weeks of trastuzumab completion, we collected clinical information, systolic/diastolic echocardiographic measures, high-sensitivity troponin I, B-type natriuretic peptide, and VO ₂ peak using a cycle ergometer. Regression models were used to examine the association between VO ₂ peak and clinical, imaging, and cardiac biomarkers individually and in combination.
Results: Among 147 patients (age 52.2 ± 9.3 years), the mean VO ₂ peak was 19.1 ± 5.0 mL O ₂ ·kg ^-1 ·min ^-1 (84.2% ± 18.7% of predicted); 44% had a VO ₂ peak below threshold for functional independence (<18 mL O ₂ ·kg ^-1 ·min ^-1 ). In multivariable analysis, absolute global longitudinal strain (GLS) (β = 0.58; P = 0.007), age per 10 years (β: -1.61; P = 0.001), and E/e' (measure of diastolic filling pressures) (β = -0.45; P = 0.038) were associated with VO ₂ peak. GLS added incremental value in explaining the variability in VO ₂ peak. The combination of age ≥50 years, E/e' ≥7.8, and GLS <18% identified a high probability (85.7%) of compromised functional independence, whereas age <50 years, E/e' <7.8, and GLS ≥18% identified a low probability (0%). High-sensitivity troponin I and B-type natriuretic peptide were not associated with VO ₂ peak.
Conclusions: Readily available clinical measures were associated with VO ₂ peak early post-breast cancer therapy. A combination of these parameters had good discrimination to identify patients with compromised functional independence and potentially increased future CVD risk.
Competing Interests: This study was funded by an operating grant from the Canadian Institutes of Health Research (137132 and 142456); a Project Grant (1119955) from the National Health and Medical Research Council, Australia; an unrestricted grant from General Electric Healthcare; and personnel support from the Ontario Early Research Award. Dr Bonsignore is supported by the Canadian Institute of Health Research Fredrich Banting Doctoral Award. Dr Amir has received fees for expert testimony from Genentech/Roche. Dr Abdel-Qadir is supported by a National New Investigator Award from the Heart and Stroke Foundation of Canada; and has received honoraria from Amgen. Dr Wintersperger has received research support and speaker honorarium from Siemens Healthineers; and provides consultation to Bayer AG. Dr Haykowsky is funded by the Research Chair in Aging and Quality of life in the Faculty of Nursing at University of Alberta. Dr Thavendiranathan is supported by the Canadian Institutes of Health Research New Investigator Award (147814) and a Canada Research Chair in Cardio-oncology; and has received speaker honoraria from Amgen, Boehringer Ingelheim, and Takeda. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(© 2021 The Authors.)