Multifactorial impacts on early breast carcinogenesis

Multifactorial impacts on early breast carcinogenesis – assessing the combined effects of preventable factors on breast cancer using a novel Organ-On-a-Chip platform

The alarming incidence of breast cancer worldwide cannot be explained solely by hereditary factors. Evidence suggests that extrinsic factors, such lifestyle and environmental contaminants (e.g. endocrine disrupting chemicals, EDCs), play a role in breast cancer development, but research linking EDCs to cancer is currently inconclusive. This is mainly due to the fact that most EDCs are studied individually at concentrations that don’t reflect realistic exposures. However, we are exposed to a large cocktail of chemicals, some of which may have an effect when acting together. Similarly, when considering the preventable risk factors (those that can be prevented by changes in lifestyle and behaviour) no single factor has yet been shown to account for the overall cancer risk, suggesting a multitude of contributors may be involved. Our project addresses this knowledge gap by investigating the combined role of a mixture of EDCs together with saturated fats (reflecting a high fat diet – a factor that has been suggested to increase cancer risk) on breast carcinogenesis. We use an innovative Organ-On-a-Chip tool that integrates a flow-through system and three-dimensional in vitro breast cell cultures. By using this model, which closely resembles the breast tissue in women, we study how mixtures of EDCs present in human tissues acts together with lifestyle factors to affect breast cancer risk. Our aim is to advance our understanding of how multifactorial risks of cancer can be minimised by preventing or reducing the exposure to factors that contribute to the overall risk.