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.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.2Consecutive 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.2Among 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.2Readily 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.2