Exercise, weight loss and biomarkers for breast cancer risk

Background: Postmenopausal breast cancer is the most prevalent cancer in Western women. There are several known risk factors for postmenopausal breast cancer of which few are lifestyle-related and, thereby, modifiable. These risk factors provide an opportunity for primary prevention. In this thesis, we estimated that one out of four (25.7%) breast cancer cases in the Dutch female population of >40 years is attributable to lifestyle, i.e., overweight/obesity, physical inactivity, alcohol consumption, insufficient dietary fibre intake and smoking. Methods: The Sex Hormones And Physical Exercise (SHAPE)-2 trial aims to investigate the effect of weight loss, with or without exercise, on sex hormones (primary outcome) and other breast cancer risk biomarkers in postmenopausal, overweight-to-obese and inactive women. Women were randomised to a diet group (n=97), an exercise group (n=98) or control (n=48). Both intervention groups had the aim to lose 5-6 kg bodyweight. The diet group was prescribed a diet with a deficiency of 500 kcal/day. The exercise group followed an intensive exercise programme of 4 h/wk and was prescribed a caloric intake restriction of 250 kcal/day. Body composition, abdominal fat, physical fitness, serum sex hormones, inflammatory markers and adipokines and quality of life were measured at baseline and after 16 weeks. Results:Both the diet (-4.9 kg) and exercise group (-5.5 kg) achieved the target weight loss. The control group remained weight stable (+0.06 kg). Weight loss by exercise resulted in a significantly larger fat loss compared to diet-only, whereas lean mass was preserved. Subcutaneous and intra-abdominal fat decreased with both weight loss programmes. Subcutaneous abdominal fat decreased to a larger extent with exercise than with diet. Fitness increased in the exercise group only. Weight loss, either by diet or exercise, resulted in significantly favourable effects on sex hormones (decreased) and sex hormone binding globulin (SHBG; increased). Exercise induced larger favourable effects on most hormones, of which some reached significance. These effects of exercise on sex hormones seem to be largely mediated by the larger amounts of fat loss. HsCRP and leptin reduced by both diet- and exercise-induced weight loss. There was a suggestively larger effect of exercise on hsCRP compared with diet. No effects were seen on IL-6 and adiponectin. Change in total body fat affected sex hormone levels more than a change in abdominal fat. In influencing markers of inflammation and adipokines, change in abdominal fat seemed of more or equal importance. Weight loss resulted in a positive change in self-perceived health, which was significantly greater in the exercise group compared with diet. Conclusions: Weight loss, by diet or mainly exercise, produces favourable effects on body composition and breast cancer risk biomarkers in healthy postmenopausal women. Weight loss by exercise in combination with a small caloric intake restriction leads to more beneficial health outcomes, including physical fitness, body composition and self-perceived health status, than equivalent weight loss induced by diet only. The larger reduction in fat mass experienced with exercise leads to larger decreases in serum sex hormone levels indicating a decrease in breast cancer risk. In addition to a decrease in total body fat, exercise may also result in larger decreases of abdominal fat, which could possibly affect markers of breast cancer risk through other pathways