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Chemoprevention of Breast Cancer by Mimicking the Protective Effect of Early First Birth. Addendum
Final addendum rept. 2 May 2012-2 Feb 2012
UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
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Breast terminal duct lobular unit tissue cell proliferation and estrogen and progesterone receptor expression ER and both PRA and PRB have been studied by immunohistochemistry in four protocols relating to chemoprevention 1 parous and nulliparous women 2 women in the first trimester of pregnancy 3 women briefly exposed to high levels of estrogen secondary to ovarian stimulation and 4 women using oral contraceptives OCs with the same estrogen dose but markedly different doses of the progestin, norethisterone. Further related studies are currently being completed. Pregnancy reduced PRA expression and cell proliferation and lower PRA distinguished parous from nulliparous women, but PRA levels were not reduced with short-term high levels of estrogen. Results from our study of high levels of progestin exposure will be available shortly. Most importantly, reducing the dose of the progestin in an OC by 60 failed to reduce cell proliferation, due it appears to marked increases in receptor levels. Results from our study of reducing the estrogen dose while keeping the progestin dose constant in an OC will be available shortly. Early in this grant we showed that breast tissue was overwhelmingly concentrated in dense tissue. Pregnancy reduces mammographic density and long-term breast cancer risk study of a large autopsy series and the results discussed above suggest that the protection is due to a reduction in breast tissue and in its cell proliferation rate. We successfully identified a set of breast tissue gene expression changes that distinguish parous from nulliparous rats and mice a critical step in the testing of possible experimental chemoprevention approaches. We showed that, in the rat, estradiol, estradiol plus progesterone, and -HCG are protective against carcinogen-induced mammary cancer. Progesterone alone was not. We are currently testing this effect of -HCG in women funded by another grant.
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