With breast cancer incidence continuing to increase and now impacting 1 in 7 women we need to unravel the biological and molecular determinants of risk so we can develop precision preventatives for those most at risk. This project funding will allow me to define how postmenopausal obesity doubles the risk of developing hormonally driven breast cancer. The first step towards precision preventatives.– Associate Professor Kara Britt
Background
Post-menopausal women who are obese are particularly susceptible to developing breast cancer, yet it is not clear why. Whilst the obese breast tissue has been shown to produce factors associated with increased risk of developing breast cancer, their direct effect on the epithelial cells in the breast (the cells that give rise to breast cancer) has not been determined. Additionally, we do not know if the immune system’s ability to suppress tumour development is compromised in obese women. If we want to provide strong public health messages to women to watch avoid obesity, or develop drugs to assist them managing it we need to understand exactly how obesity promotes breast cancer.
Aims and objectives
Our multi-disciplinary team provides expertise in obesity, metabolism, breast cancer initiation, immunology and normal breast development allowing us to assess many aspects of the breast. In the cancer field it has recently shown that women with a strong family history of breast cancer have pre-existing molecular changes in the breast cells, making them susceptible to breast cancer. Here we will determine if postmenopausal obesity leads to changes in normal breast cells, similar to that seen in women at high risk of familial cancer (ie: BRCA1 driven). As well as the changes to the breast cells themselves, we also know that the immune system is an important part of early breast cancer control. Our team has already shown that the increased risk of cancer seen in women who have not had children, or those with dense breasts, is associated with changes in their immune system that impair its ability to fight cancer. We will use our expertise to determine if obesity also impacts the immune system’s ability to suppress the very first steps of cancer development. This is important to work out as it tell us which cells we need to try and help work more efficiently to block cancer development.
How it will be done
We have strong collaborations with plastic surgeons who perform breast reduction surgeries and provide the surgical tissue for research. We will obtain breast tissue from lean and obese postmenopausal women to count the breast cell types including immune cells and also look at the changes in genes (the cells blueprint for how to work) that occur with obesity. We know anti-obesity drugs like ozempic can reduce weight in women and mice. Here we will test if the ozempic driven weight loss is associated with a decrease in cancer risk in mice and how this occurs.
Potential impact
Prevention strategies to date have had limited impact on breast cancer incidence. The long-term goal of our research is to help women to become motivated to maintain a healthy BMI to reduce their breast cancer risk by informing them of the way that obesity results in cancer. However, to complement this, we also need to develop personalised therapies that are specific to their situation that block obesity-driven breast cancer and be delivered with minimal side effects in these otherwise well women.