Correlation between tamoxifen elimination and biomarker recovery in a primary prevention trial

A. Guerrieri-Gonzaga, L. Baglietto, H. Johansson, B. Bonanni, C. Robertson, M. T. Sandri, L. Canigiula, C. Lampreda, S. Diani, E. A. Lien, A. Decensi

Research output: Contribution to journalArticle

Abstract

We have shown previously that a reduction from the conventional dose of tamoxifen is associated with a comparable modulation of circulating biomarkers, including insulin-like growth factor-I and cholesterol. In the present study, we have correlated serum tamoxifen elimination with biomarker recovery in healthy subjects completing a 5-year intervention period. Tamoxifen, N-desmethyltamoxifen, and biomarker levels were measured at 0 (baseline), 2, 4, and 6 weeks after completion of treatment in 23 healthy postmenopausal women allocated to tamoxifen 20 mg/day and in 6 women allocated to placebo. Mean (±SD) serum tamoxifen and N-desmethyltamoxifen concentrations were, respectively, 141 ± 50 and 226 ± 77 ng/ml at baseline, 36 ± 19 and 99 ± 46 at 2 weeks, 20 ± 15 and 61 ± 37 at 4 weeks, and 12 ± 9 and 36 ± 26 at 6 weeks. Serum tamoxifen and N-desmethyltamoxifen half-lives were 9 and 13 days, respectively. Body mass index was associated positively with drug's serum half-life. Compared with baseline values, the percentage increase in total cholesterol, low-density lipoprotein cholesterol, and insulin-like growth factor-I 4 weeks after treatment completion was 5, 9, and 14%, respectively. No change during the 6-week period was observed in the placebo arm. Our findings indicate that the biomarker recovery is slower than serum tamoxifen elimination, suggesting that low tamoxifen concentrations may still exert a biological effect. In addition, the prolonged half-life of tamoxifen and metabolite provides the rationale for a weekly administration of the drug in a preventive context. However, the clinical implications of our findings remain to be defined.

Original languageEnglish
Pages (from-to)967-970
Number of pages4
JournalCancer Epidemiology Biomarkers and Prevention
Volume10
Issue number9
Publication statusPublished - 2001

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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