Exercise decreases Neuregulin-1 concentrations in HER2+ breast cancer patients

Abstract Purpose Trastuzumab used for the treatment of patients with HER2-positive breast cancer can induce cardiotoxicity. While the Nueregulin-1(NRG1)/HER pathway plays a central role in human cardiovascular physiology, the link between exercise, NRG1 and cardiotoxicity remains unclear The study aimed to assess the effect of a 12-week supervised exercise training on circulating NRG1 levels. A secondary objective was to assess the correlation between NRG1 level and cardiotoxicity. Methods Patients were randomized to receive either adjuvant trastuzumab in combination with a training 12-week supervised exercise program in a training group (training group, TG) or trastuzumab alone (control group, CG). Cardiorespiratory fitness test left ventricular ejection fraction and circulating level of NRG1 were assessed before, after and 3 months after training. Results Eighty-nine patients were randomized (TG; n = 46 ; CG; n = 43) with 76 having a baseline NRG1 concentration available. After the exercise program, plasma levels of NRG1 significantly decreased in the TG (mean difference − 0.20 ng/ml ; 95% CI, -0.32, -0.07) whereas they remained stable in the CG (mean difference − 0.05 ng/ml; 95% CI, -0.20, 0.10). NRG1 remain stable during follow up. However, no correlation was observed between NRG1 changes and either cardiorespiratory fitness (peak V̇O2) and Left Ventricular Ejection Fraction (LVEF) (R = 0.087, p = 0.53; R =-0.157, p = 0.26 and R =-0.131, p = 0.33 respectively). Conclusion A 12-week interval training program significantly decreased NRG1 concentration in HER2-positive breast cancer patients treated with adjuvant trastuzumab therapy. This change was not associated with peak V̇O2 nor LVEF. Trial registration: This trial was registered with ClinicalTrials.gov under the number NCT02433067.