Chemoprevention of Breast Cancer by Mimicking the Protective Effect of Early First Birth

We have shown in the rat that pregnancy, and also estradiol, estradiol plus progesterone, and beta-HCG are protective against mammary cancer; associated RNA expression changes have been identified. No definitive evidence was obtained of parity or hormonal prevention of mammary cancer in mice. Breast gene expression in parous and nulliparous women showed marked between-women differences but failed to distinguish parous from nulliparous women. ER and PR expression, and cell proliferation in the breast epithelium has 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 estrogen levels; and (4) women using oral contraceptives with markedly different progestin doses. Further studies are ongoing. Pregnancy reduced PRA expression and lower PRA distinguished parous from nulliparous women. Analysis of the results of women exposed to high estrogen levels and women using oral contraceptives with markedly different progestin doses is ongoing. Pregnancy reduces mammographic density and breast cancer risk. How these are related has been studied in a large autopsy series; results suggest that part of the protection may be the result of a reduction in breast epithelium; further studies of these samples are ongoing.
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