Fenretinide breast cancer prevention trial: drug and retinol plasma levels in relation to age and disease outcome.
Fenretinide breast cancer prevention trial: drug and retinol plasma levels in relation to age and disease outcome.
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发表时间：
2003
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通讯作者：
F. Formelli;T. Camerini;E. Cavadini;V. Appierto;M. G. Villani;Alberto Costa;G. D. de Palo;M. D. Di Mauro-M.
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作者：
F. Formelli;T. Camerini;E. Cavadini;V. Appierto;M. G. Villani;Alberto Costa;G. D. de Palo;M. D. Di Mauro-M.
在参与预防乳腺癌试验的女性中评估芬维A胺（4-HPR）药物和视黄醇水平与第二次乳腺癌风险的关系，考虑年龄和绝经状态。方法：在一项多中心预防试验中，早期乳腺癌妇女被随机分配接受不治疗或200 mg/d的4-HPR治疗5年。在基线时和干预期间每年从Istituto Tumori（米兰，意大利; 4-HPR组和对照组分别为818例和756例，占试验参与者的53%）招募的女性中采集血液。采用高效液相色谱法测定4-HPR及其主要代谢产物N-（4-甲氧基苯基）维A酰胺和视黄醇的血药浓度。分析中考虑了三个年龄范围（或≥ 56岁）、基线时的绝经状态和中位随访97个月时的疾病结局。结果：基线视黄醇水平显著低于治疗前水平（P =46岁vs = 0.71; P <0.001）。结论：血浆视黄醇水平随年龄增长和绝经后增加，与乳腺癌复发无关。4-< 45岁受试者的HPR水平低于老年受试者。在年轻女性中观察到的药物血浆水平和4-HPR预防效果之间的反比关系表明4-HPR血浆隔离在4-HPR生物活性中的作用。
OBJECTIVES To assess, in women participating in a breast cancer prevention trialon fenretinide (4-HPR), the relationship of drug and retinol levels with the risk of second breast malignancy, taking into account age and menopausal status. METHODS In a multicenter prevention trial, women with early breast cancer were randomly assigned to receive no treatment or 200 mg of 4-HPR/day for 5 years. Blood was collected at baseline and on a yearly basis during intervention from women recruited at the Istituto Tumori (Milan, Italy; 818 and 756 in the 4-HPR and control arm, respectively, who accounted for 53% of the participants in the trial). The plasma concentrations of 4-HPR, its main metabolite N-(4-methoxyphenyl) retinamide, and retinol were assayed by high-performance liquid chromatography. Three age ranges (or=56 years), menopausal status at baseline, and disease outcome at a median follow-up of 97 months were taken into account in the analysis. RESULTS Baseline retinol levels were significantly lower (P or=46 years versus or= 0.71; P <or= 0.001) related to pretreatment retinol levels. CONCLUSIONS Retinol plasma levels increased with age and after menopause and were not related to breast cancer recurrence. 4-HPR levels were lower in subjects < 45 years than in older subjects. The inverse relationship between drug plasma levels and 4-HPR preventive effects observed in young women suggests a role for 4-HPR plasma sequestration in 4-HPR biological activity.