title: Evidence of altered autonomic cardiac regulation in breast cancer survivors.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Breast cancer survivors show multiple dysfunctions: vagal impairment, lower aerobic fitness, signs of altered metabolism, and higher perception of fatigue.
  
  
  CONCLUSIONS
  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.
authors.affiliation: BIOMETRA Department, University of Milan, Milan, Italy.|Exercise Medicine Unit, Humanitas Clinical and Research Center, Via Alessandro Manzoni, Rozzano, 56, 20089, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Vigo
authors.affiliation: Breast Unit, Humanitas Cancer Center, Rozzano, Milan, Italy.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Gatzemeier
authors.affiliation: BIOMETRA Department, University of Milan, Milan, Italy.|Exercise Medicine Unit, Humanitas Clinical and Research Center, Via Alessandro Manzoni, Rozzano, 56, 20089, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Sala
authors.affiliation: BIOMETRA Department, University of Milan, Milan, Italy.|Exercise Medicine Unit, Humanitas Clinical and Research Center, Via Alessandro Manzoni, Rozzano, 56, 20089, Milan, Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Malacarne
authors.affiliation: Cancer Center, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: Armando
authors.initials: A
authors.lastname: Santoro
authors.affiliation: BIOMETRA Department, University of Milan, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Pagani
authors.affiliation: BIOMETRA Department, University of Milan, Milan, Italy. daniela.lucini@unimi.it.|Exercise Medicine Unit, Humanitas Clinical and Research Center, Via Alessandro Manzoni, Rozzano, 56, 20089, Milan, Italy. daniela.lucini@unimi.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Lucini
mesh_terms: D000328:Adult; D000368:Aged; D001341:Autonomic Nervous System / Q000503:physiopathology*; D001342:Autonomic Nervous System Diseases / Q000453:epidemiology* / Q000503:physiopathology; D017704:Baroreflex / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D001943:Breast Neoplasms / Q000453:epidemiology / Q000503:physiopathology*; D016022:Case-Control Studies; D005080:Exercise Test; D005221:Fatigue / Q000503:physiopathology; D005260:Female; D006321:Heart / Q000294:innervation*; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008875:Middle Aged; D012307:Risk Factors; D017741:Survivors / Q000706:statistics & numerical data*
keywords: Autonomic nervous system; Baroreflex sensitivity; Cardiometabolic risk; Cardiorespiratory fitness; Lifestyle; Secondary prevention