The synthetic retinoid HPR (N-4-hydroxyphenil retinamide), a derivate of retinioic acid, has been shown to inhibit N-nitroso-N-methylurea induced mammary carcinogenesis (1). It also exhibits an antiproliferative effect on rat mammary epithelium that may be involved in HPR inhibition of mammary caracinogenesis (2). HPR has also been found to block the combined proliferative effects of insulin and prolactin upon the mammary epithelium growing in vitro. Preliminary studies indicate that this retinoid is less toxic than other known retinoids (3) and that it can be administered to humans with the aim to demonstrate its efficacy in preventing or treating some specific types of cancer. Due to the peculiar concentration of HPR in the mammary glands, a priority will be given to the study of its effectiveness in breast cancer. As the group of patients more at risk for this cancer are women already operated for a breast tumor, the capability of HPR to prevent contralateral cancer of the breast will be evaluated. The incidence of contralateral breast cancer is about 0.8% per year and a group of about 5,000 patients is needed to demonstrate the effectiveness of the drug in reducing the rate of second primaries in the other gland. The applicant institution will evaluate HPR with a randomized clinical trial in which about 5,000 patients treated for stage one breast cancer, who remained with no evidence of disease and who did not receive adjuvant endocrine or chemotherapy treatment will enter in three years. Patients will be followed-up every four months for at least seven years.
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