Effects of high and low-to-moderate intensity exercise during (neo-)adjuvant chemotherapy on muscle cells, cardiorespiratory fitness and muscle function in women with breast cancer: Protocol for a randomized controlled trial (Preprint)

UNSTRUCTURED Background: (Neo-)adjuvant chemotherapy for breast cancer is effective but has deleterious side effects on muscle tissue resulting in reduced skeletal muscle mass, muscle function and cardiorespiratory fitness. Various exercise regimens during cancer treatment have been shown to counteract some of these side effects. However, no study has compared the effect of high intensity training vs. low-to moderate intensity training on muscle tissue cellular outcomes and function in breast cancer patients during chemotherapy. The aim of the present sub-study within the Phys-Can consortium, is to evaluate and compare the effects of high and low-to-moderate intensity exercise on muscle cellular outcomes, muscle function and cardiorespiratory fitness in women with breast cancer undergoing (neo-)adjuvant chemotherapy. We further aim to investigate if chemotherapy including taxanes have different effect in muscle than taxane-free chemotherapy. Methods: Eighty women, recently diagnosed with breast cancer scheduled to start (neo-)adjuvant chemotherapy will be randomized to a combination of strength and endurance training, either at high intensity or at low-to-moderate intensity. Testing of muscle function and cardiorespiratory fitness and collection of muscle biopsies from m. vastus lateralis will be performed before the first cycle of chemotherapy (or, when not possible, one week after) (T0), halfway through chemotherapy (T1), and after completion of chemotherapy (T2). It is estimated that approximately 50% of the participants will be willing to take muscle biopsies. To separate the effect of the treatment itself, a usual care group with no supervised training will also be included, and in this group testing and collection of muscle biopsies will be performed at T0 and T2 only. Results: Inclusion started in December 2016 and the last participant is expected to complete the intervention in December 2022. Discussion: The present study will generate new knowledge about the effects of different training intensities for women with breast cancer during chemotherapy treatment. It will give further insight into how chemotherapy affects muscle tissue and how physical training at different intensities may counteract treatment side effects in muscle. The results from this study will inform the development and refinement of exercise programs that are effective and compatible with multidisciplinary management of breast cancer.