BREAST CANCER PREVENTION WITH SYNTHETIC RETINOID (HPR)

合成维甲酸HPR(N-4-羟基苯基维甲酰胺)，其衍生物 维甲酸可抑制N-亚硝基-N-甲基脲诱导的 乳腺癌发生(1)。它还显示出一种抗增殖作用。 大鼠乳腺上皮细胞可能参与HPR抑制作用的研究 癌变(2)。HPR也被发现阻止了合并 胰岛素和催乳素对乳腺上皮细胞增殖的影响 在体外生长。 初步研究表明，这种维甲酸的毒性比其他 已知的维甲酸(3)，它可以用在人类身上，目的是 证明其对某些特定类型的预防或治疗效果 癌症的威胁。 由于hpr在乳腺中的特殊浓度，优先考虑 将致力于研究其治疗乳腺癌的有效性。作为 患这种癌症的风险更高的患者是已经做过手术的女性 对于乳腺肿瘤，HPR预防对侧癌症的能力 乳房的大小将被评估。 对侧乳腺癌的发病率每年约为0.8%， 需要约5,000名患者组成的小组来证明 这种药物能降低另一腺体的二次初发率。 申请机构将通过随机临床试验评估hpr。 在这项试验中，约有5000名患者接受了一期乳腺癌的治疗， 他们没有疾病的证据，也没有接受佐剂治疗 内分泌或化疗将在三年内进入。病人 将每四个月随访一次，持续至少七年。

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.