Grant: Project Grant

There is a strong association between chronic inflammation, and the risk of developing cancer. One of the most prevalent examples of chronic inflammation is obesity, which affects over 1/3 of adults in Canada/USA. Inevitably, obesity now rivals smoking as the #1 preventable risk factor for cancer. Obesity is associated with higher incidence of breast cancer metastasis (i.e. cancer spread), particularly to liver and lung. Of particular interest is lung metastasis, given the high frequency of breast cancer progression to this site in patients, and the association between obesity and multiple lung-inflammatory conditions (e.g. asthma). Despite that 1/3 of adults are overweight/obese, the vast majority of preclinical studies are focused on how breast cancer spreads in lean models. We recently determined that lung tissue becomes severely altered in response to obesity. We found that the abundance and the behaviour of certain immune cells within the lungs are drastically changed with weight gain, creating an environment that can nourish cancer cells that have spread to this organ. Importantly, we have found that weight loss is sufficient to reverse obesity-associated lung inflammation and breast cancer metastasis. These are significant findings because the lung is one of the most frequent sites of metastasis, which causes death in patients. The objective of this study is to provide a translational framework for understanding how overweight/obesity affects breast cancer metastasis, with the goal of identifying blood-based prognostic markers and new therapies. This could improve treatment methods for a large proportion of breast cancer patients, and contribute to a broader understanding of the relationship between the immune system and cancer. We hypothesize that breast cancer progresses differently in obese patients compared to lean patients, and therefore, obese patients will require different treatment considerations.