Breast cancer risk and resistance : a balancing act

We have shown that the p53 pathway is subject to hormonal regulation and contributes to the decrease in breast cancer risk afforded by a full term pregnancy. The importance of the p53 pathway in breast tissue is also evident because breast cancer is the most common tumor type among women with Li-Fraumeni syndrome who have inherited mutations in TP53, but penetrance can vary among individuals. Variation in penetrance is extreme in mice as ~60% BALB/c-Trp53+/- females develop mammary tumors while mammary tumors are rarely observed in C57BL/6-Trp53+/- females. The lecture will focus on our efforts to define the duplicitous roles of estrogen in stimulating proliferation while also activating p53 and to map the modifiers of mammary tumor risk in p53-deficient mice. These pathways provide pathways that can be harnessed for precision diagnostics and therapeutics.