Enhancing muscle strength and immunity in breast cancer
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Introduction: Regular exercise reduces mortality and recurrence in breast cancer survivors, but we don’t know why. Similarly, breast cancer survivors with stronger and larger muscles have better overall survival and lower recurrence than women with weaker and smaller muscles. The long-term goal of this study is to reduce mortality and recurrence in breast cancer survivors by increasing the number who engage in regular exercise and resistance training. We hope to achieve this by providing a method to monitor their prognosis after exercise as a way to empower them to make informed decisions about their exercise habits. The goal of the proposed study is to take the first steps to understanding whether exercise improves prognosis in breast cancer survivors because it improves anti-cancer type immunity. That information will be used to identify markers in the blood that can be used to monitor the benefit of exercise. 
 Central hypothesis: We have recently published that amongst people with gastrointestinal (GI) cancer those who have the strongest and largest muscle mass also have the strongest immune system. This is clinically relevant because cancer patients who have a strong immune system have a better prognosis than those with a weaker immune system. In the current study we propose the central hypothesis that increasing muscle strength and mass through exercise and muscle resistance training reduces mortality and the risk of cancer recurrence in breast cancer survivors because it improves the capacity of the immune system to attack and eliminate cancer cells. 
 Questions and how we reached them: The immune system is made up of many types of cells and proteins. Some immune cells called CD8 T cells can kill cancer cells. Other T cells, called regulatory or Treg cells can stop immune cells from working. In our GI cancer study we found that there are more cancer-killing CD8 T cells and fewer Treg cells in the patients with stronger and larger muscles and that the opposite is true for cancer patients with weaker and smaller muscles. The primary goal of the study will be addressed in Specific Aim 1 where we ask the question: If breast cancer survivors increase their muscle strength by engaging in regular muscle strengthening exercises, does the number of CD8 T cells increase and regulatory T cells decrease? In a secondary analysis of the data we will ask the question: Is the link between CD8 T cell and Treg cell numbers and muscle strength the same for breast cancer survivors as it is for GI cancer patients? (Specific Aim 2). The relationship between muscle and T cells suggests that they communicate with each other. Muscle can release a variety of molecules and proteins into the blood that T cells can bind to. Once bound, T cells respond to these molecules and proteins by modifying their behavior. As part of our secondary analysis we ask: Do breast cancer survivors with higher levels of muscle-derived molecules and proteins in the blood have stronger muscles, more CD8 T cells and fewer Treg cells? (Specific Aim 3). Cells, molecules and proteins in the blood that increase with exercise and with increasing muscle strength and mass will be considered potential markers to be used to identify breast cancer survivors who would benefit by resistance training and monitor the benefit of a resistance training program. 
 General methodology: Thirty non-exercising breast cancer survivors will take part in a 16-week muscle resistance training protocol designed to increase muscle strength and mass. Before and after the 16-week program a blood sample will be collected and the numbers of different types of T cells and levels of muscle-derived molecules and proteins will be measured. At the same time, muscle strength will be measured using a handgrip strength test and the amount of muscle each participant has will be measured using a DEXA scan to image the whole body. The data generated will be analyzed and changes in levels of muscle strength, mass, T cell subsets, muscle-derived molecules and proteins before and after resistance training will be determined using the Student t test or Wilcoxon signed ranked test, as appropriate. Correlations between levels of muscle strength and mass, T cell subset frequencies and levels of molecules and proteins will be determined using Spearman correlation. 
 Innovative elements and potential impact: To our knowledge, we are the first to publish a relationship between skeletal muscle strength and mass and the anti-cancer T cell immune profile. In the proposed study we will test the novel concepts that i) skeletal muscle strength and mass in breast cancer survivors is linked to a weak anti-cancer T cell immune profile, and that ii) as muscle strength and mass increases during resistance training, the anti-cancer T cell immune profile improves. The data generated might be used to identify blood markers that can be used to i) monitor the benefit of resistance exercise training in breast cancer survivors, and ii) identify breast cancer survivors who are at risk of recurrence and who would benefit by resistance exercise training. The same biomarkers might also be used to design exercise programs focused on improving survival and reducing recurrence in women with breast cancer.