Cardiorespiratory fitness, adiposity, and metabolic risk in breast cancer survivors: links with circulating WISP-1 and WISP-3.

Breast cancer survivors (BCS) often exhibit persistent metabolic and hepatic disturbances after cancer treatment; however, cardiorespiratory fitness's (CRF) underlying molecular signatures and associations of CRF with metabolic and hepatic health remain insufficiently understood. We examined whether circulating metabolic markers and WNT1-inducible signaling pathway proteins (WISPs) differ between BCS and matched controls, as well as whether CRF relates to metabolic and hepatic risk within BCS. To this end, 40 BCS and 40 age- and weight-matched healthy controls underwent assessment vis-à-vis anthropometrics, fasting metabolic biomarkers, liver enzymes, and fatty liver index (FLI). CRF was estimated using a standardized step test. Circulating WISP-1 and WISP-3 were quantified by enzyme-linked immunosorbent assays. Compared with controls, BCS exhibited lower CRF and higher body fat percentage, fasting insulin, insulin resistance, liver enzyme levels, and FLI. Circulating WISP-1 was higher in BCS, even after adjusting for age, menopausal status, and body fat percentage (adjusted ratio 1.23, 95% CI 1.01-1.52; p < 0.05). Differences in insulin resistance and hepatic risk were attenuated after adjustment, while the between-group difference in WISP-3 was not significant after covariate adjustment. Among BCS, higher CRF was associated with lower insulin resistance, reduced hepatic risk, and lower prevalence of FLI > 30 (57.9% vs. 20.0%, p < 0.05) and metabolic syndrome (57.9% vs. 5.0%, p < 0.001), while WISP concentrations did not differ by CRF. BCS demonstrated persistent metabolic vulnerability and elevated circulating WISP-1, regardless of adiposity and menopausal status. The findings show that higher CRF was associated with lower metabolic and hepatic risks.