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A new paradigm for African American breast cancer involving stem cell differentiation
Breast cancer survival among African-American (AA) women 5 years after diagnosis is 74% compared to 88% among white women. Increasing data, including the higher incidence of ER negative tumors in AA women, supports the hypothesis that intrinsic biologic differences exist in AA breast tissue compared with white breast tissue. Our laboratory has developed and published a novel tissue engineering system for human mammary epithelial cells. It allows for unusually long-term (>3 months) establishment of normal primary cultures that differentiate into complex organotypic architecture including branching ducts and lobules. The ability to form human ductal structures is unprecedented in the literature. We show that tissue from AA women forms ductal structures significantly faster than tissue from white women, and that, samples from AA women are 40% more likely to show this differentiation. This is consistent with the idea that stem cells provide the capacity to form ductal structures. We hypothesize that intrinsic biological differences exist between AA and white breast tissue. We further hypothesize that differences in the proportions of pluripotent adult stem cells or stem cell potency are responsible for the observed differences in differentiation potential. Using a prospective study design, we will investigate the behaviors of cultured breast epithelium derived from AA and white women. Samples of breast tissue from breast reduction mammoplasties will be obtained from 38 AA and 38 white women. These numbers will provide us with >80% power to observe a difference similar to that seen in the pilot study. Culture over 30 days will be evaluated for time and onset of differentiation, harvested, labeled with stem cell markers and evaluated by flow cytometry. With this sample size, we will extend our analysis to potential modifiers of differentiation, including age, parity, BMI and hormone usage. Using a standard questionaire we will obtain data on other modifying factors: breast cancer risk factors and environmental exposure data. If our hypothesis is true, then one might expect a higher incidence of breast cancer in the AA population or a higher mortality (with a stem cell population more likely to form an aggressive tumor type). Our unique breast tissue engineering system, combined with the efforts of the Pittsburgh Center for Minority Health will enable our laboratory to address a fundamental issue involving the etiology of AA breast cancer.
African-American (AA) women are more likely to die from breast cancer. Increasing data, such as the higher incidence of ER- tumors in AA women, supports the hypothesis that there may be fundamental differences in AA breast tissue. Our laboratory has developed a new tissue engineering system for human mammary epithelial cells. This system allows for unusually long-term establishment of normal primary cultures that are capable of re-forming breast architecture, including ducts and lobules, in the culture dish. The ability to form ductal structures from human breast tissue is absolutely unique to our laboratory. Preliminary work done in the lab showed that tissue from AA women formed ductal structures faster than tissue from white women, and that samples from black women were 40% more likely to show this development in culture. We believe that stem cells are the basis of the ductal structures observed in our culture system. We hypothesize that fundamental differences exist between AA and white breast tissue that can be demonstrated by the ability of this tissue to form ducts in culture. We further hypothesize that it is the proportion or activity of the stem cells present in the breast that is responsible for these differences. Samples of breast tissue from equal numbers of AA (n= 38) and white (n= 38) breast reduction mammoplasties will be obtained using the community outreach initiative BWHOLE of the Pittsburgh Center for Minority Health. This tissue will be cultured for 30 days, evaluated for the formation of breast architecture, and analyzed for the proportion of stem cells present. With this sample size we will have the statistical power to analyze potential modifiers of the capacity to form ducts in culture, including age, number of live births, body mass index and hormone usage. We will also obtain data on breast cancer risk factors and environmental exposure from a standard questionnaire. We have found a specific characteristic of AA breast tissue that may tell us why AA breast cancer is more aggressive and more lethal than breast cancer in white women. Knowing this we can develop treatment regimens that are targeted to the AA community. This unique breast tissue engineering system combined with the efforts of the Center for Minority Health will enable our laboratory to address a fundamental issue involving the cause and incidence of African American breast cancer.