This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Formelli, F. Articles by Veronesi, U. Search for Related Content PubMed PubMed Citation Articles by Formelli, F. Articles by Veronesi, U.

Fenretinide Breast Cancer Prevention Trial

Drug and Retinol Plasma Levels in Relation to Age and Disease Outcome¹

Istituto Nazionale Tumori, 20133 Milan, [F.F., T.C., E.C., V.A., M.G.V., G.D.P., M.G.D.M.]; S. Maugeri Foundation, Pavia [A.C.]; and Istituto Europeo di Oncologia, 20133 Milan [U.V.], Italy

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 (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.

This article has been cited by other articles:

				A. Micheli, E. Meneghini, G. Secreto, F. Berrino, E. Venturelli, A. Cavalleri, T. Camerini, M. G. Di Mauro, E. Cavadini, G. De Palo, et al. Plasma Testosterone and Prognosis of Postmenopausal Breast Cancer Patients J. Clin. Oncol., July 1, 2007; 25(19): 2685 - 2690. [Abstract] [Full Text] [PDF]

				M. G. Villani, V. Appierto, E. Cavadini, M. Valsecchi, S. Sonnino, R. W. Curley, and F. Formelli Identification of the Fenretinide Metabolite 4-Oxo-Fenretinide Present in Human Plasma and Formed in Human Ovarian Carcinoma Cells through Induction of Cytochrome P450 26A1 Clin. Cancer Res., September 15, 2004; 10(18): 6265 - 6275. [Abstract] [Full Text] [PDF]