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.