Attenuated pressor and sympathetic neural responses to exercise in long-term breast cancer survivors: role of the muscle metaboreflex

Previous studies have reported blunted increases in blood pressure during physical exercise in cancer survivors treated with cardiotoxic chemotherapy. However, the sympathetic neural mechanisms underlying this attenuated response remain unknown. We hypothesized that long-term breast cancer (BC) survivors exhibit impaired muscle metaboreflex function, which would partially explain the reduced sympathetic cardiovascular responses to exercise. Nineteen BC survivors [age 49 ± 2 yr; body mass index (BMI) 27 ± 1 kg/m^2] and 14 sex-, age-, and BMI-matched controls (age 48 ± 2 yr; BMI 26 ± 1 kg/m^2) were studied. Muscle sympathetic nerve activity (MSNA; microneurography), mean arterial pressure (MAP; Finometer), stroke volume, cardiac output, and total peripheral resistance (SV, CO, and TPR; Modelflow), and heart rate [HR; electrocardiogram (ECG)] were continually measured at baseline, during 3 min of static handgrip (HG) at 30% maximal voluntary contraction, followed by postexercise ischemia (PEI) to isolate muscle metaboreflex activation. BC survivors were evaluated ≈9 yr after treatment completion. Changes in MAP during HG were attenuated in BC survivors versus controls, and this difference persisted during PEI (Δ12.0 ± 2.0 mmHg vs. 21.0 ± 2.0 mmHg; P = 0.001). Similarly, the MSNA burst frequency response to HG was lower in BC survivors than controls, and the difference remained during PEI (Δ3.0 ± 1.0 bursts/min vs. 9.0 ± 1.0 bursts/min; P = 0.001). SV and CO were reduced during HG in BC survivors (P < 0.05) but not during PEI. No group differences were observed in HR or TPR. Collectively, these findings indicate that the attenuated pressor and sympathetic neural responses to exercise in long-term BC survivors are explained, at least in part, by attenuated muscle metaboreflex control. NEW & NOTEWORTHY Long-term breast cancer (BC) survivors previously treated with doxorubicin- and trastuzumab-based chemotherapy show reduced muscle metaboreflex activation, which partly explains attenuated pressor and sympathetic neural responses to exercise in this population. Importantly, these findings shed light on the blunted exercise-induced blood pressure increase observed in long-term BC survivors.