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Does Lactation Mitigate Triple Negative/Basal Breast Cancer Progression?

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Annual summary (rev) 1 Sep 2011-31 Aug 2012

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Young African American women have an increased risk of developing aggressive forms of breast cancer i.e. triple negativebasal-like than young non-Hispanic white women. Recent epidemiological data show increased risk of basal-like breast cancer with increased childbearing in African American women 1, 2. Breast cancers associated with a recent pregnancy pregnancy-associated breast cancer are more likely to be metastatic 3. We predict that the triple negativebasal-like breast cancer subtype is promoted by a recent pregnancy, accounting in part, for the poor prognosis of young African American breast cancer patients. We have previously reported the development of our murine intraductal mammary model 4, 5 to examine the effect of host reproductive status on the progression of early stage human breast cancer. Our model delivers human mammary tumor cells and HCC70 cell lines directly through the intact mouse teat into the correct anatomical location for ductal carcinoma in situ DCIS without surgical manipulations. Using the model to assess the effects of host reproductive status on DCIS progression, we found that DCIS progression to locally invasive disease occurred with progressive loss of myoepithelial cell differentiation markers. The loss of p63 was identified as an early indicator of compromised myoepithelium. Further, our data suggest that the protective myoepithelial cell layer may be preferentially compromised by tumors formed in postpartum involuting mammary glands but maintained by pregnancy. Our murine mammary intraductal model of human breast cancer provides a rigorous approach to study early stage-tumor progression, and is well suited to study the effect of the host reproductive state on DCIS progression. Since occult tumors in women develop within ducts, we propose that this teat injection model will aid research of early disease progression, a requisite for research focused on breast cancer prevention and inhibit

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  • Medicine and Medical Research

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