Mr Joseph Wrin

While breast cancer is the most commonly diagnosed cancer in women, it represents an even more serious disease in premenopausal women. Women under 40 are more likely to be diagnosed with triple negative cancer, a sub-type for which there are no targetted therapies available and are therefore treated with chemotherapy alone. As a result, young women face a poorer prognosis than women developing breast cancer later in life.

An important element in the development breast cancer is menstrual cycling. Women having children, having children at a young age, having more than one child and breastfeeding their babies are all factors that reduce the risk of developing breast cancer. And this is because all of these events stop the menstrual cycle. During the cycle, the ductal epithelial tissue in the breast proliferates and form structures called alveoli in preparation for a pregnancy. If no pregnancy eventuates, the alveolar structure become apoptotic and regress. Macrophages remove the dying alveoli and, in so doing, generate and anti-inflammatory microenvironment in the breast, which is similar to a wound-repair state. This involves tissue remodeling and angiogenesis, but also the suppression of pro-inflammatory immune surveillance that detects and destroys early neoplastic events. More menstrual cycles mean more proliferation and more opportunity for the accumulation of cell division-related mutations, which is exacerbated by the anti-inflammatory environment that allows cancers to take hold.

A key component in the removal of dying epithelium in the breast is the complement component C1q. C1q recognises phosphatidylserine and calreticulin on the surface of apoptotic cells and bridges them to macrophages via CD91 and CD93. In mouse models, the lack of C1q leads to a build-up of apoptotic cells in the mammary gland and a seven-fold decrease in the incidence of carcinogen-induced mammary tumours. This implies the lack of C1q allows normal immune surveillance during mammary gland regression and a decrease in mammary tumour development. It also presents an opportunity to develop a therapeutic intervention able to inhibit breast cancer formation. I am working to develop a monoclonal antibody for use as a breast cancer preventative agent as well as a possible treatment for triple negative disease in premenopausal young women. This antibody is currently in development and I have great hopes for its efficacy and translation to the clinic.