spinodyssey

"Mammary Gland Microenvironmental
in Breast Cancer Metastasis after Pregnancy"
My research addresses the question of why breast cancer, when diagnosed within close proximity to a recent pregnancy, is more aggressive and more likely to spread. The term pregnancy associated breast cancer, or PABC for short, by definition refers to breast cancer that is diagnosed within a few years of a completed pregnancy. PABC is currently associated with poor prognosis and high rates of metastasis. While a pregnancy early in life is protective with regards to breast cancer risk, a pregnancy later in life appears to contribute to breast cancer risk. The average PABC patient is between the ages of 32 and 38. These new mothers are almost twice as likely to die from their disease, making the societal impact of PABC very high. Today, as more women delay child-bearing, the cases of breast cancer diagnosed within close proximity to a completed pregnancy is anticipated to rise. Increase in breast cancer risk following pregnancy has been shown to persist for 10 years after a completed pregnancy. Thus, conservative estimates show that 30,000-40,000 cases of breast cancer in 2007 could be complicated by a recent pregnancy. We predict that the process of involution, the remodeling of the mammary gland back to a pre-pregnant state soon after birth if the mother does not nurse or post-weaning if she does, results in an environment that allows tumor cells that would normally remain dormant to become active.

We are currently developing mouse models of PABC to utilize for determination of molecules that are specifically altered in the tumor environment of PABC. We have preliminary evidence from these models that the involution environment promotes tumor formation, promotes increased tumor size, promotes tumor spread in the primary tissue, and decreases tumor latency. We are now examining whether the animals in this study also have an increase in metastasis. Finally, we will examine the tumor environment in these animals to determine molecules that may be altered in PABC. From these molecules we will develop a database of candidate markers for PABC. Then, markers will be evaluated on clinical samples to determine if they are important predictors of survival and metastasis. Markers discovered by this study will create an opportunity for future targets of therapeutic intervention and prevention in young women at risk for PABC
in the post-partum setting.

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