Grant: Project Grant

Pregnancy-associated breast cancer is rare overall with about 120 cases each year in Canada. In one study, 30% of pregnancy-associated breast cancer patients were born with a mutation in the BRCA1 gene. In another study, the incidence of pregnancy-associated breast cancer in female carriers of a BRCA1 mutation was much greater than the expected incidence. We hypothesize that the loss of BRCA1 function disturbs the process of cell division that is required in the human breast to prepare for lactation. When this process is disturbed, we believe the cellular environment of the breast also changes and, together, these alterations predispose the breast to early onset breast cancer. To study this hypothesis, we will examine mammary cells isolated from genetically modified mice, mammary cells isolated from human donors, and immortal human mammary cells that have been genetically-modified. Our multidisciplinary and international research team has expertise in the study of oriented cell division, cytokinesis, and mammary stem cells. We believe that our studies will provide a more detailed understanding of the pathways altered in a pregnancy-associated breast cancer. This better understanding, in turn, will provide us with an opportunity to develop new therapies that target the disturbed molecular mechanisms, which we will also test in the proposed research. Thus, new prophylactic drug treatments and novel insight into suboptimal development of alveolar cells are plausible clinical applications for the findings from our proposed studies.