Grant: Team Grant: Bringing Biology to Cancer Prevention - Breast Cancer

About four out of every five women who inherit a BRCA1 mutation will develop breast cancer in their lifetimes. Currently, removal of both unaffected breasts (bilateral mastectomy) is the only option to significantly reduce this risk; however, most women with a BRCA1 mutation choose to undergo annual screening with MRI, which is aimed at earlier detection rather than prevention. It has been 30 years since this gene was discovered; it is time we identify a non-surgical option to prevent breast cancer for this high-risk population. Our proposal focuses on a pathway that prepares the breast for lactation (breastfeeding) after childbirth. The overall goal is to evaluate whether a safe and inexpensive drug called 'cabergoline' which is normally used to stop lactation (milk production) may also prevent breast cancer by targeting this same pathway, avoiding the need for preventative surgery. Our research team will bring together national and international experts to study a new idea that is based on several lines of evidence, including: i.) experimental studies indicating that the biology needed to prepare the breast for lactation is disrupted in women who carry a BRCA1 mutation; ii.) epidemiological work suggesting these women are more likely to experience difficulties in breastfeeding leading to an increased risk; and excitingly, iii.) preclinical research that will evaluate whether a readily available, inexpensive and well-tolerated drug (cabergoline) can reduce the risk of breast cancer in BRCA1 carriers with negligible side-effects. We will leverage over two decades of expertise and existing infrastructure to investigate these three pillars, providing evidence to offer a personalized strategy for the primary prevention of breast cancer in young BRCA1 carriers.