Fenretinide breast cancer prevention trial: Drug and retinol plasma levels in relation to age and disease outcome

Franca Formelli, Tiziana Camerini, Elena Cavadini, Valentina Appierto, Maria Grazia Villani, Alberto Costa, Giuseppe De Palo, Maria Gaetana Di Mauro, Umberto Veronesi

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)34-41
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Issue number1
Publication statusPublished - Jan 1 2003

ASJC Scopus subject areas

  • Epidemiology
  • Oncology


Dive into the research topics of 'Fenretinide breast cancer prevention trial: Drug and retinol plasma levels in relation to age and disease outcome'. Together they form a unique fingerprint.

Cite this