BREAST CANCER CHEMOPREVENTION WITH SYNTHETIC RETINOID (H

本研究的目的是评估综合治疗的有效性。 维甲酸，非维甲酸N-(4-羟基苯基)维甲酰胺，HPR，预防 已经接受乳腺癌手术的患者的对侧原发肿瘤。 HPR是维甲酸的一种衍生物，已被证明可以抑制 N-亚硝基-N-甲基脲诱发乳腺癌。它还展示了一个 大鼠乳腺上皮细胞增殖抑制作用可能参与 HPR对乳腺癌发生的抑制作用HPR也被发现阻止了 胰岛素和催乳素联合应用对人脐静脉内皮细胞增殖的影响 乳腺上皮细胞在体外生长。此外，HPR是一个相对非 有毒的维甲酸，与许多其他维甲酸不同的是，它不会在 肝脏，但在脂肪组织和乳房。申请人 该机构已经证实，这种靶向集中也存在于人类和 已经完成了一项为期一年的关于101例乳腺癌的随机I期研究 建议服用非维甲酸200毫克/天的患者 每月有三天的禁药假期，防止身体受损的风险 夜视仪。由于HPR的独特集中，米兰癌症 该研究所于1987年3月开始了一项随机临床试验，以评估 这种维甲酸降低对侧乳房发病率的能力 癌症，在手术后大约十年内每年增长约1%。这个 申请机构及其在意大利北部的分支机构计划随机 多达5000名腋窝淋巴结阴性的乳腺癌患者，没有 疾病的证据，以及没有接受任何佐剂内分泌或 化疗。 患者随机接受hpr 200 mg/d治疗，对照组接受治疗，并进行随访 每五个月进行一次体检和每年一次的胸部X光、骨骼检查 每18个月进行一次扫描或骨骼X光检查，并每年进行乳房X光检查 对侧乳房。后续将至少持续一段时间 七年，几年。自1987年3月以来，314名患者在 治疗组310例，对照组310例。没有对侧的初选 被记录下来了。

The aim of this study is to evaluate the effectiveness of the synthetic retinoid, fenretinide N-(4hydroxyphenyl) retinamide, HPR, in preventing contralateral primaries in patients already operated on for breast cancer. HPR is a derivative of retinoic acid and it has been shown to inhibit N-nitroso-N-methylurea induced mammary carcinogenesis. It also exhibits an antiproliferative effect on rat mammary epithelium that may be involved in HPR inhibition of mammary carcinogenesis. HPR has also been found to block the combined proliferative effects of insulin and prolactin upon the mammary epithelium growing in vitro. Moreover, HPR is a relatively non toxic retinoid which, unlike many other retinoids, does not accumulate in the liver but in adipose tissure and in the breast. The applicant institution has confirmed this targeted concentration also in humans and has completed a one year randomized Phase I study on 101 breast cancer patients indicating that the recommended dose for fenretinide is 200mg/day with a three day drug holiday every month to prevent the risk of impaired night vision. Due -Lo the unique concentration of HPR, the Milan Cancer institute started in March 1987 a randomized clinical trial to evaluate the capability of this retinoid to reduce the incidence of contralateral breast cancer which is about 1% per year for about ten years after surgery. The applicant institution and its branches in Northern Italy plan to randomize up to 5,000 breast cancer patients with negative axillary lymphnodes, no evidence of disease and who did not receive any adjuvant endocrine or chemotherapy treatment. Patients are randomized for HPR 200mg/d by versus control and followed up every five months with physical examination and annual chest X-rays, bone scan or skeleton X-rays every 18 months and annual mammography of the contralateral breast. The follow-up will be continued for at least seven,years. Since March 1987,314 patients have been randomized in the treated group and 310 in the control group. No contralateral primaries have been recorded.