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 (VOpeak) (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 VOpeak using a cycle ergometer. Regression models were used to examine the association between VOpeak and clinical, imaging, and cardiac biomarkers individually and in combination.

Results: Among 147 patients (age 52.2 ± 9.3 years), the mean VOpeak was 19.1 ± 5.0 mL O·kg·min (84.2% ± 18.7% of predicted); 44% had a VOpeak below threshold for functional independence (<18 mL O·kg·min). In multivariable analysis, absolute global longitudinal strain (GLS) (β = 0.58; 0.007), age per 10 years (β: -1.61; 0.001), and E/e' (measure of diastolic filling pressures) (β = -0.45; 0.038) were associated with VOpeak. GLS added incremental value in explaining the variability in VOpeak. 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 VOpeak.

Conclusions: Readily available clinical measures were associated with VOpeak 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.