Inflammation and the tumour microenvironment in breast cancer: The role of Stat3 and NF-kB

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Breast cancer is a common disease in post-menopausal women. Although surgery and chemotherapy prolong life, many breast tumours spread to other organs and this metastatic disease causes the death of the patient. There is evidence from epidemiological studies that, although pregnancy can reduce the lifetime risk of breast cancer, women have a higher risk in the 5-10 years following a pregnancy. We propose that this risk is due to the factors that are present in the breast during the period immediately following lactation (involution), when the milk-producing cells die and secrete a number of inflammatory substances. Our studies on the processes that take place during involution have identified some of these factors. In this project, we propose to delete two signaling molecules that are key regulators of involution and measure the effect this has on tumour formation in models of breast cancer. Once we have identified the most important factors, we will compare levels of these in cell lines derived from breast cancer tissues. We will then specifically block these factors in breast cancer cells and measure how this affects their growth and spread in a novel tissue scaffold that we are developing to provide a 3-D model of the breast. It is hoped that this work will reveal new therapeutic targets or markers of breast cancer.