Evidence of altered autonomic cardiac regulation in breast cancer survivors

Purpose: Surgery and adjuvant therapy improved prognosis of breast cancer survivors. This improvement risks being offset by potential late-occurring cardiovascular toxicity of oncologic treatment and increased cardiometabolic risk profile associated with lifestyle changes. We address the hypothesis that in breast cancer survivors, multiple functional alterations might define a phenotype, characterized by vagal impairment, diminished aerobic fitness, increased metabolic risk, and reduced wellbeing. Methods: We studied 171 sedentary asymptomatic women (106 cancer survivor—65 controls) of similar age (53 ± 8.6; 51 ± 8.1 years). Autonomic regulation was evaluated by autoregressive spectral analysis of R wave to R wave (RR) interval and systolic arterial pressure variability. Aerobic fitness was directly assessed by cardiopulmonary exercise test. Body mass index (BMI) and waist circumference served as proxies of metabolism. Fatigue and stress-related symptoms were evaluated with validated questionnaire. Results: Patients showed significantly smaller total RR variance (1644 ± 2363 vs 2302 ± 1561 msec²), smaller absolute power of low frequency (LF) (386 ± 745 vs 810 ± 1300 msec²) and high frequency (HF) (485 ± 1202 vs 582 ± 555 msec²) of RR interval variability and smaller spontaneous baroreflex sensitivity (15.0 ± 8.9 vs 21.9 ± 10 msec/mmHg), suggesting vagal impairment. VO₂ peak and O₂ pulse were lower in cancer survivors than in controls. Fatigue and stress-related somatic symptoms scores were higher, as was BMI and waist circumference. Conclusion: Breast cancer survivors show multiple dysfunctions: vagal impairment, lower aerobic fitness, signs of altered metabolism, and higher perception of fatigue. Implications for Cancer Survivors: We propose that the concept of clinical phenotype, which may accommodate multiple functional disturbances, might be useful in long-term personalized prevention programs for breast cancer survivors.