Objectives: To assess, in women participating in a breast cancer prevention trial on 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 (≤45, 46-55, and ≥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 ≤ 0.05) in subjects ≤ 45 years than in older subjects, and among subjects in the age range 46-55 years, they were significantly higher (P ≤ 0.001) in those in postmenopause than in those in premenopause. Baseline retinol levels were not related to the risk of a second breast malignancy. 4-HPR and N-(4-methoxyphenyl)retinamide levels were not affected by menopausal status. They slightly, but significantly (P ≤ 0.05), increased with age (≤46 years versus ≤45 years) but only in disease-free subjects. Among subjects <45 years, they were slightly, but significantly (P ≤ 0.05), higher in those subjects in which breast cancer recurred. 4-HPR treatment caused a retinol level reduction, which was strongly (r ≥ 0.71; P ≤ 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.
|Number of pages||8|
|Journal||Cancer Epidemiology Biomarkers and Prevention|
|Publication status||Published - Jan 1 2003|
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