The muscle mass, omega-3, exercise, diet and lifestyle study (MODEL): For women after completion of breast cancer treatment

Abstract

Body weight and composition change after treatment for breast cancer are important considerations when investigating factors affecting risk of disease-free survival. Concurrent loss of lean body mass (LBM) and increase in body fat is common after treatment for breast cancer and are related to the development of metabolic disease. Shorter observational studies have reported significant associations between body composition changes, inflammation, cardiac death and increased risk of metabolic syndrome. Thus, studies that aim to increase the understanding of how body composition change affects outcomes in this population are required. Numerous studies have investigated the mechanisms and quantity of body fat change, however, quantity and causes of LBM loss after treatment are not fully understood.Exercise interventions have been shown to improve body composition (LBM and body fat%), waist girth, aerobic fitness and other risk factors for metabolic syndrome without reducing body weight. Nutrition interventions have been shown to reduce body weight and body fat% that is accompanied with an improvement in metabolic health. However, the reduction in weight includes potentially detrimental reductions in LBM and significantly increased risk of sarcopenia. The combination of nutrition plus exercise seems to maintain LBM and elicit concurrent body fat and/or body weight reductions. Long chain omega-3 fatty acids (LCn-3) have been associated with improved cardiometabolic health, have a theoretical yet inconsistent effect on adiposity, are associated with decreased inflammation, and more recently have been shown to improve the response of LBM to an anabolic stimulus. Thus, they present as a relevant clinical option for this population, yet no evidence currently exists after treatment for breast cancer. Therefore, this PhD research had two aims: the primary aim was to examine the independent and combined effects of an exercise and nutrition program and LCn-3 supplementation on LBM change, QOL and chronic inflammation soon after completion of treatment for breast cancer. This was done by conducting a 6-month 3-arm randomised controlled trial that compared three conditions: 1) LCn3 supplementation only (N-3); 2) LCn-3 supplementation plus a 12-week group exercise and nutrition lifestyle program (Ex+N-3); and, 3) the lifestyle program plus placebo - olive oil (Ex+OO). The secondary aim was to explore baseline cross-sectional associations between body composition (in particular LBM) and LCn-3 intake, treatment, demographical and lifestyle factors after completion of treatment for breast cancer. For the scope of this PhD thesis, the investigation targeted women who had completed treatment of breast cancer within the last 12 months, and were considered ‘disease free’ at entry to the trial. The thesis is presented as both unpublished work, and a series of published and submitted manuscripts. Due to slower than expected recruitment, 49 participants were included in the trial, and were generally representative of women who have been diagnosed with breast cancer in Australia. In the six month randomised controlled trial, all three groups experienced maintenance of LBM, with no significant differences between groups after 24 weeks. Compared to women who consumed LCn-3 supplements or participated in the lifestyle program separately, those exposed to both interventions were more likely to experience a greater amount of body weight and waist and hip girth reduction. Quality of life (QOL) improved for all groups, while C-reactive protein (CRP) levels did not change throughout the intervention. Secondary analyses indicated that LCn-3 supplementation was associated with improved physical function and maintenance of grip strength independent of exercise and nutrition. Limitations of the intervention were lower than expected recruitment rate, and the effectiveness of the resistance training program may have been reduced as a result of the use of elastic resistance equipment. In terms of the secondary aim (cross-section at baseline), after adjusting for weight and age, the major determinants of LBM after treatment were higher levels of aerobic fitness and the ability to perform a greater number of push ups. Erythrocyte levels of LCn-3, energy and protein intake, CRP and treatment related variables were not associated with body composition after treatment for breast cancer. This thesis provides new insight into the synergy of LCn-3 and an exercise and nutrition lifestyle program in a population of women who have been treated for breast cancer. Combining LCn-3 supplementation with best practice nutrition and exercise advice is a consideration for clinicians aiming to prevent and improve adverse body composition change after treatment. Longer-term research investigating the preventive effect of LCn-3 and exercise on development of metabolic syndrome and breast cancer related morbidity and mortality should be undertaken. Finally, our novel findings indicate that muscle function is strongly associated with weight adjusted LBM after treatment, and its use as a measure of health warrants further investigation in determining the overall health of breast cancer survivors.