One hundred eligible women with breast cancer were recruited between August 1, 2012 and December 31, 2016. The protocol and informed consent were approved by the institutional review board (HS-12-00141) and participants gave written informed consent. Participants were <6 months post-treatment for stage I-III female breast cancer and were nonsmokers, sedentary (<60 minutes of structured exercise/week), with body mass index (BMI) ≥25.0 kg/m2 or body fat >30% and waist circumference >88 cm.
RRS was calculated using gender specific validated methodology (4), at baseline and week 17. The following data were collected in order to calculate RRS: age, SBP, hsCRP, TC, HDL-C, HbA1c, current smoking status, and parental history of myocardial infarction. Due to the primary study design, current smokers were ineligible and therefore smoking status did not vary by patient. Age and parental history of myocardial infarction were abstracted from medical records. SBP was measured three times using the arm contralateral to the affected breast with an automated sphygmomanometer after five minutes of quiet sitting, (Welch Allyn, Skaneateles Falls, New York). Plasma and serum biomarkers were analyzed from fasting (≥12 hours) blood samples that were stored at -80°C until batch analysis at study completion. The following RRS equation was used to calculate 10-year cardiovascular disease risk (%) = [1 − 0.98634(exp[B − 22.325])] × 100% where B = 0.0799 × age + 3.137 × natural logarithm (SBP) + 0.180 × natural logarithm (high-sensitivity C-reactive protein) + 1.382 × natural logarithm (TC) −1.172 × natural logarithm (HDL-C) + 0.134 × HbA1c (%) (if diabetic) + 0.818 (if current smoker) + 0.438 (if family history of premature myocardial infarction).
The 16-week exercise intervention was designed based on American College of Sports Medicine/American Cancer Society exercise guidelines for cancer survivors (>150 minutes of aerobic exercise and 2-3 days of resistance exercise training/week) (8, 9). Women participated in thrice weekly supervised one-on-one exercise sessions for 16 weeks. Days one and three endorsed resistance and aerobic exercise of approximately 80 minutes. Day two included approximately 50 minutes of aerobic exercise. Aerobic exercise included treadmill walking, rowing machine, or stationary cycling. Heart rate was monitored throughout the aerobic exercise sessions to maintain the heart rate at 65% to 80% maximum heart rate. Resistance exercise sessions included leg press, leg flexion, leg extension, chest press, seated row, bicep curls, and triceps pulldowns. Initial resistance was set at 80% of 1-repetition maximum (1-RM) for lower body exercises and 60% 1-RM for upper body exercises which were determined during baseline testing.
The sample size was based on changes in insulin with a 16-week exercise intervention among survivors of breast cancer. Enrollment of 100 women provided 80% statistical power (p<0.05) to detect a 2.6-mU/mL (SD=4.0 mU/mL) difference in mean insulin levels, assuming 20% dropout using a two-group t test. Within-group and between-group differences in mean change for individual outcomes measured at 16 weeks were evaluated using general linear models repeated-measures analyses of variance and mixed model repeated-measures analysis, respectively. A priori covariates with potential associations with the outcome of interest (e.g., type of treatment [chemotherapy, radiation, or both], surgery-type, medication use [e.g., anti-hypertensives and hyperglycemia medications], BMI, caloric intake, diet quality, and macronutrient distribution) were explored in models, but none modified the results. Analyses were performed using SAS (SAS/STAT User’s Guide, Version 9.4; SAS Institute, Cary, NC).