BREAST CANCER PREVENTION WITH SYNTHETIC RETINOID

本研究的目的是评估合成的有效性 维甲酸，芬维A胺N-（4-羟基苯基）维A酰胺，HPR，预防 对侧原发灶的乳腺癌患者已经进行了手术。 HPR是视黄酸的衍生物，已显示其抑制 N-亚硝基-N-甲基脲诱发乳腺癌。它还展示了一个 对大鼠乳腺上皮细胞的抗增殖作用，可能涉及 HPR抑制乳腺癌发生。HPR也被发现可以阻止 胰岛素和催乳素的联合增殖作用对 体外培养的乳腺上皮细胞。此外，HPR是一种相对非 与许多其他类维生素A不同， 肝脏，但在脂肪组织和乳房。申请人 研究机构已经证实，这种有针对性的浓度也在人类和 完成了一项为期一年的随机I期研究，研究对象为101例乳腺癌患者。 表明芬维A胺推荐剂量为200 mg/天的患者 每个月有三天的药物假期，以防止受损的风险 夜视由于-Lo独特的浓度HPR，米兰癌症 研究所于1987年3月开始了一项随机临床试验，以评估 这种类维生素A降低对侧乳腺癌发生率的能力 在手术后的大约十年里，每年大约有1%的癌症。的 申请机构及其在北方意大利的分支机构计划随机 多达5，000名腋窝淋巴结阴性的乳腺癌患者， 有疾病证据且未接受任何辅助内分泌或 化疗 患者被随机分为HPR 200 mg/d组和对照组，并随访 每五个月进行一次身体检查，每年进行一次胸部X光检查， 每18个月进行一次扫描或骨骼X光检查， 对侧乳房随访将持续至少 七年了。自1987年3月以来，314名患者被随机分配到 对照组310例。没有对侧的主动脉 被记录下来。

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.