In the SHAPE-2 study, we aim to investigate the potential effect of physical activity on biomarkers of breast cancer risk (sex hormones), additional to weight loss. We hypothesize that exercise-induced weight loss results in a stronger decrease in serum sex hormones compared with equivalent diet-induced weight loss and compared with controls.
The goal of the intervention, and challenge in this trial, is for subjects to lose an equivalent amount of 5–6 kg of body weight in both intervention groups. Success of the study depends heavily on subjects’ adherence and motivation.
We implemented several strategies to increase adherence and motivation of the study subjects. First, the weight loss interventions are delivered by experienced dietitians and physiotherapists, who are situated in the municipality and easily accessible. For participants in the intervention groups, we scheduled a high contact frequency with the dietitian and physiotherapists which is proven to be a relevant success factor for weight reduction . Second, group sessions are implemented in both intervention programmes which provide a combination of social support, a healthy dose of competition and increase self-efficacy . It is also suggested that dietary group sessions produce greater weight loss effects than individual counselling alone . Groups are kept small to secure enough room for interactions and tailoring of the programme to the specific needs of the participants. Third, to strengthen motivation of the participants and for monitoring purposes, the researchers visit diet and exercise group sessions regularly. Furthermore, participants receive newsletters about the study or related topics and the study website is updated frequently.
Adherence of the control group is also a challenge. We expect women allocated to the control group to be disappointed since they have their mind set on losing weight. This might lead to a change in lifestyle, either conscious or unconscious, resulting in slight weight loss. To anticipate, we repeatedly stress the importance of the control group. Moreover, we offer an evenly attractive alternative weight loss programme starting at the end of the study.
This trial has a strict time schedule. We aim to include 25–30 participants per municipality in a small time window, since the participants have to start simultaneously with the group interventions. The first group starts at the central research site in the Utrecht region. Inclusion in the second participating region (Enschede) starts in parallel. Consecutive groups within one region start after a minimum time interval of 1 month.
Due to a consecutive inclusion of municipalities, the winter season, summer holidays and national holidays (e.g. Christmas) might affect the adherence of some study groups. To retain compliance in order to achieve the same weight loss goal, dietitians and physiotherapists will anticipate these circumstances. We pay extra attention to the Nordic walking programme in winter since the colder climate and shorter days may threat compliance. We therefore provide more options for supervised Nordic walking hours and reflective clothing in winter.
In our study, we will measure visceral and subcutaneous abdominal fat by using MRI, which is a highly sensitive technique to measure changes in (intra-)abdominal fat. A side effect of the use of cross sectional imaging in healthy subjects is that there is a risk of incidental findings. Rates of over 30% have been described while the proportion of subjects that might benefit from these findings is likely to be much lower than the proportion that will have no or even an adverse effect [54, 55]. Outweighing the risk-benefit ratio and ethical considerations , we decided on the following procedure. The non-contrast enhanced T1-weighted IDEAL scans are considered non-diagnostic and therefore will not be routinely reviewed by a radiologist. If researchers encounter an apparent finding that strikes them as a possible abnormality, the radiologist will be consulted. When the finding is of potential clinical relevance, the participant and their general practitioner will be informed and advised on further work up.
Our trial is the first study especially designed to assess the additional effect of exercise on sex hormone levels when equivalent weight loss is achieved. Four former exercise intervention studies in the field suggested an interplay between sex hormones and body weight/fat mass [22–26]. Greater weight loss produced greater effects on serum sex hormone levels and SHBG.
The question remains whether there is an additional effect of exercise on serum sex hormones, as breast cancer risk biomarkers, when equivalent weight loss is reached. In the SHAPE-2 study, we aim to investigate the potential effect attributable to physical activity on postmenopausal breast cancer risk biomarkers, in addition to weight loss.