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    Research Grants Awarded

    Human prolactin as a chemopreventive agent for breast cancer

    Study Section:
    RISK and Prevention, Epidemiology

    Scientific Abstract:
    Background: The American Cancer Society estimates that this year, approximately 200,000 new cases of breast cancer will be diagnosed in the US , and roughly 40,000 women will die of this disease. The magnitude of this continuing problem together with the failure of conventional chemotherapies against advanced invasive breast cancer demands a shift of emphasis in cancer research from treatment to prevention. Objectives/Hypothesis : It has long been known that early full-term pregnancy significantly reduces women’s risk to have breast cancer. We hypothesize that one of the reasons that early pregnancy reduces breast cancer risk is early exposure of the breast to prolactin (PRL), a female hormone that is responsible for the breast differentiation and milk production. Differentiated breast epithelium is far less susceptible to carcinogenesis. Our hypothesis is supported by our recent finding that PRL and HER2/neu bi-transgenic mice have drastically lower breast tumor rates as compared to that of HER2/neu transgenics. Therefore, the objective of this proposal is to test if early application of PRL will elicit the protective effects in the breast similar to those induced by pregnancy and result in reduced breast tumor rate in HER2/neu transgenic mice. Specific Aims/Study Design : Aim 1. To administer PRL to HER2/neu transgenic mice at an early age by slow-releasing Alzet mini-pumps with various regimens to determine (a) the feasibility and (b) the necessary duration of using PRL as a chemopreventive agent to reduce the risk of breast cancer; Aim 2. To identify the morphological changes, biomarker and genomic signatures in PRL treated mice using mammary gland whole mounts, Western blots and cDNA microarrays, which can be used to guide future clinical studies. Potential Outcomes and Benefits of the Research: With more and more American women delaying the birth of their first child to a later age, it is important to develop a simple and effective means to reduce this obvious breast cancer risk factor. We believe that a short-term treatment with PRL offers a potential solution. The fact that hPRL is a non-toxic protein with well-defined functions in the breast makes it more attractive as a chemopreventive agent since there will be no foreseeable side effects after a relatively short-term application. A positive result from this pilot study could easily translate to clinical trials and have a significant impact on breast cancer prevention.

    Lay Abstract:
    Background: The American Cancer Society estimates that this year, approximately 200,000 new cases of breast cancer will be diagnosed in the US , and that roughly 40,000 women will die of this disease. The magnitude of this continued problem together with the failure of conventional chemotherapies against advanced invasive breast cancer demands a shift of emphasis in cancer research from treatment to prevention. Objectives/Hypothesis : It has long been known that early full-term pregnancy significantly reduces women’s risk to have breast cancer. We hypothesize that one of the reasons protection is conferred by early pregnancy is exposure of the breast to a female hormone, prolactin (PRL), which is responsible for breast “maturation” and milk production. After lactation, the matured breast cells shift from those that are highly susceptible to those that are resistant to carcinogenesis. Our hypothesis is supported by our recent finding that bi-transgenic mice, that have elevated PRL along with an oncogene product, HER2/neu, have drastically lower breast tumor rates as compared to HER2/neu transgenic mice. Our main objective, therefore, is to test whether we can reduce the breast cancer rate by early application of PRL to young female HER2/neu transgenic mice that are highly susceptible to breast tumor. Specific Aims/Study Design : Aim 1. To administer PRL to female HER2/neu transgenic mice at an early age by slow-releasing mini-pumps with various durations to determine (a) the feasibility and (b) the necessary duration of using PRL as a chemopreventive agent to reduce the risk of breast cancer. Aim 2. To identify the morphological changes, biomarkers, and genomic signatures of PRL treatment, which can be use to guide future clinical studies. Potential Outcomes and Benefits of the Research: With more and more American women delaying the birth of their first child to a later age, it is important to develop a simple and effective means to reduce this obvious breast cancer risk factor. We believe that a short-term early treatment with PRL offers a potential solution. The fact that PRL is a non-toxic protein with well-defined functions in the breast makes it more attractive as a chemopreventive agent since there will be no foreseeable side effects after a relatively short-term application. A positive result from this pilot study could easily translate to clinical trials and have a significant impact on breast cancer prevention.