Correlation between tamoxifen elimination and biomarker recovery in a primary prevention trial.
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.
Guerrieri-Gonzaga
A
A
Division of Chemoprevention, European Institute of Oncology, 20141 Milan, Italy.
Baglietto
L
L
Johansson
H
H
Bonanni
B
B
Robertson
C
C
Sandri
M T
MT
Canigiula
L
L
Lampreda
C
C
Diani
S
S
Lien
E A
EA
Decensi
A
A
D000368:Aged; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008875:Middle Aged; D017698:Postmenopause; D020845:Selective Estrogen Receptor Modulators / Q000097:blood / Q000493:pharmacokinetics*; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*
D015415:Biomarkers; D008078:Cholesterol, LDL; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D007334:Insulin-Like Growth Factor I; D002784:Cholesterol; C028787:N-desmethyltamoxifen