Gravidomimetic Prevention of Breast Cancer

Albany Medical College, Albany NY

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Abstract

Alpha-fetoprotein (AFP) is one of the agents of pregnancy that affords significant reduction in risk of acquiring breast cancer to women who experience term pregnancy. AFP stops the growth of estrogen-dependent human breast cancer xenografts. It is no toxic, and its mechanism of action is different from that of agents currently used in the clinic to treat breast cancer. We have identified the minimal active site of AFP, which is octapeptide, and we have synthesized and purified this 8-mer peptide and several analogs that are even more effective than the parent peptide. These small, potent peptide significantly the that are even more effective than the parent peptide. These small, potent peptides significantly inhibit the estrogen-stimulated growth of normal mouse uterus (a screening assay), they inhibit the growth of human T47D breast cancer in humans. The specific aims of this Cancer Prevention Small Grant program pilot project proposal are to demonstrate that the peptides will prevent cancer in an animal model and to assess serum for markers of cancer status. The hypothesis is that administration of peptide to N-methyl N-nitrosourea treated rats will decrease tumor incidence as well as tumor burden induced by the carcinogen. The research design will follow that of Grubbs' studies in which carcinogen-treated rats are either mated (to provide the protection afforded by pregnancy) or treated with test agent (to mimic pregnancy's protective effect). Reduction of tumors in the experimental animals is compared to that in the mated animals and in non-treated controls. Serum samples are collected for assessment of markers that may indicate breast cancer presence, progression, or regression. There is need for additional agents, with novel mechanisms of action, for the prevention of estrogen-receptor-positive breast cancer. The need is underscored by the observation that currently used chemopreventives for breast cancer are not without adverse side effects. The octapeptide has a noel anti-estrotrophic mechanism. Moreover, it blocks tamoxifen-stimulated uterine growth. Therefore it has potential to be used alone as well as in combination for the chemoprevention of breast cancer.