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Abstract:
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Breast and ovarian cancer are leading causes of cancer-related deaths among women, responsible for over 56,000 fatalities annually in the United States. Women at increased risk for breast cancer are often also at increased risk for ovarian cancer, reflecting common risk factors for both diseases. Studies of ovarian cancer prevention are limited as compared to those of breast cancer primarily due to difficulties in ovarian tissue sampling and low incidence of the disease. However, this may be overcome by developing dual target prevention drugs. In the present study, three common breast cancer carcinogen models [7,12-dimethylbenzanthracene (DMBA), N-methyl-N-nitrosourea (MNU) and estradiol (E2)] were combined with local ovarian DMBA administration to induce progression to breast and ovarian cancer concurrently in the rat. Six months after the initial treatment, E2/DMBA-treated rats showed the most pronounced histological changes consistent with dual cancer development. E2/DMBA-treated rats had mammary hyperplasia, atypia, ductal carcinoma in situ and/or invasive adenocarcinoma, and 50% of them developed preneoplastic changes in the ovary (ovarian surface hyperplasia and/or inclusion cyst formation) as well. These changes were accompanied by a decreased estrogen receptor alpha expression and elevated Ki-67 and cyclooxygenase-2 expression in both mammary glands and ovaries as examined by immunohistochemistry. Mammary gland morphology was normal in vehicle controls while hyperplasia was observed in
DMBA/DMBA and MNU/DMBA-treated rats; ovarian preneoplastic changes were seldom observed in any of these rats.
These studies provide a useful model for investigation of concurrent breast and ovarian cancer development and prevention. |
