Obesity and physical inactivity can increase the risk of breast cancer in postmenopausal women, contributing to approximately 15 % of cases. In the first randomized control trail, the Sex Hormones and Physical Exercise (SHAPE) study, weight or fat loss was considered essential to lower a woman’s risk of breast cancer.
These speculations led researchers to design the SHAPE 2 study, to identify whether it is purely weight loss or physical activity that lowers the risk of breast cancer.
How did you carry out your investigation?
We investigated in SHAPE-2 whether there is an additional beneficial effect of exercise beyond the effect of weight loss on hormones related to postmenopausal breast cancer risk. In the SHAPE-2 study, we included 243 postmenopausal Dutch women who were overweight and insufficiently physically active.
All women started with a four-six weeks run-in period, aiming for stable body weight. Hereafter, women were randomly allocated to one of the three following study arms for a duration of 16 weeks: a diet-induced weight loss group; a mainly exercise-induced weight loss group or a stable weight group (controls).
Women in both intervention groups had the aim to lose five to six kg of body weight. Our reasoning was that an equivalent amount of weight loss induced by diet or mainly by exercise allows us to study the additional effect of exercise on biomarkers for breast cancer risk.
Women in the diet group were prescribed a caloric restriction of 3500 kcal/week and asked to maintain their habitual physical activity level. Women in the mainly exercise group participated in a weekly exercise programme of two 1-hours sessions of fitness (aerobic and strength training) and two additional 1-hour periods of Nordic walking.
To ensure weight loss in the exercise group, a relatively small caloric intake restriction of 1,750 kcal/week was prescribed. Hormones and other outcomes were measured at baseline and after 16 weeks.
What is the link between exercise, sex hormones, and breast cancer risk?
Physical inactivity is a recognized risk factor for breast cancer, based on many prospective studies. It is estimated that around 6% of all postmenopausal breast cancer cases in the Netherlands and 16% in the US are attributable to physical inactivity.
There are several mechanisms whereby exercise might decrease breast cancer risk, e.g. by weight loss or maintenance, serum insulin, inflammatory factors, adipokines and levels of sex hormones. The strongest and most consistent evidence is available for the serum sex hormones pathway.
Relatively high levels of sex hormones (e.g. oestradiol and testosterone) in postmenopausal women are associated with a two- to three-fold increased risk of breast cancer.
What were your key findings?
We found that modest weight loss, either induced by diet or mainly by exercise, leads to reductions in sex hormone levels in postmenopausal women. Our results, furthermore, show that the somewhat more favorable exercise-effects on sex hormones are largely caused by the accompanying larger reduction in body fat when compared to diet-induced weight loss.
Since weight loss mainly induced by exercise additionally resulted in greater physical fitness, larger loss of body fat mass and preservation of lean mass, we conclude that weight loss that is induced mainly by exercise is preferred over weight loss by diet only to reduce breast cancer risk.
What are the next steps for this research? What do you hope will be achieved?
Our ultimate aim is to see fewer breast cancer cases in the future. We hope to get such an insight on the effect of weight loss and exercise on breast cancer risk that effective prevention strategies can be developed and implemented.
We need to investigate the effects of modest weight loss, either induced by diet or mainly by exercise, on other breast cancer biomarkers such as inflammatory markers. Examine the role of abdominal fat on breast cancer risk biomarkers since it could possibly affect markers of breast cancer risk through other pathways. Lastly, we will find out the dosage and type of exercise that is most important for breast cancer risk reduction and in which period of life.