Understanding factors that influence breast cancer risk, disease progression and treatment outcomes

BACKGROUND Breast cancer is the most common cancer for females in the UK, with approximately 55,000 new cases each year. Being overweight, obese, or physically inactive increases the risk of developing this prevalent disease, and although the mechanisms are not well established, it is likely that impaired anti-cancer immunity and inflammatory processes in adipose tissue have a role. For women who have developed breast cancer, a common form of treatment is neoadjuvant chemotherapy, which is administered for several months prior to surgery. Initial evidence shows that measurements of anti-cancer immunity and tumour activity, the latter through cell-free circulating tumour DNA analysis, predicts successful breast cancer treatment outcomes. It is likely that lifestyle factors, such as cardiorespiratory fitness and body composition, which also influence the success of cancer therapy, interact, but these measurements have not been assessed in parallel. AIMS AND OBJECTIVES This work will assess multiple factors, which are known to influence disease risk and treatment outcomes, both in healthy people and patients diagnosed with breast cancer. Investigations will combine immunological and genetic laboratory methodology (i.e. anti-cancer immunity and cell-free circulating tumour DNA in serum) with objective methodology for precisely assessing lifestyle (e.g. physical activity level, cardiorespiratory fitness, body composition). Investigations will probe mechanistic processes that drive tumour progression, including adipose tissue inflammation, and will investigate whether lifestyle interventions can modulate these processes. POTENTIAL APPLICATIONS AND BENEFITS/ RELEVANCE TO THE MEDICAL RESEARCH COUNCIL (MRC) This research will improve our understanding of biological processes that influence the risk of developing breast cancer and contribute towards disease progression. Importantly, in healthy people, this work will stablish whether this processes can be modified by lifestyle interventions that could be recommended to reduce cancer risk. In addition, factors predicting treatment outcomes may be stablished and validated, which could be incorporated into routine clinical practice. This research fits well within the MRC strategic plan 2014-2019, which aims at setting research priorities which are most likely to deliver improved health outcomes. For example, under research priority theme one (resilience, repair and replacement) this work provides insight into our natural protection against cancer, improving understanding of how resilience to disease breaks down and how it may be repaired with interventions that improve disease processes. In addition, under research priority theme two (living a long and healthy life), this work will provide information about lifestyles affecting health, informing the development of effective strategies for promoting healthy behaviour and tackling lifestyles that lead to disease.