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Kisanga, E.R. et al.

Kisanga, Gjerde, Guerrieri-Gonzaga, Pigatto, Pesci-Feltri, Robertson, Serrano, Pelosi, Decensi, Lien,

Tamoxifen and metabolite concentrations in serum and breast cancer tissue during three dose regimens in a randomized preoperative trial.

PURPOSE: Both therapeutic and adverse effects of tamoxifen may be related to its tissue concentrations. We investigated concentrations of tamoxifen, 4-hydroxytamoxifen, N-desmethyltamoxifen, and N-didesmethyltamoxifen in serum, normal breast, and breast cancer tissues during conventional dosage and two low-dose regimens. Furthermore we studied tamoxifen effects on the cancer proliferation marker Ki-67, and on sex hormone-binding globulin (SHBG). EXPERIMENTAL DESIGN: From September 1999 to August 2001, 120 breast cancer patients were randomized to 20-, 5-, or 1-mg tamoxifen daily. We measured serum and tissue concentrations of tamoxifen and three metabolites after 28 days of treatment, and the changes between baseline and post-treatment levels of SHBG and Ki-67. RESULTS: The median (range) tamoxifen concentrations (ng/ml) at doses of 1, 5, and 20 mg daily (n = 38, 37, and 36) were 7.5 (2.9-120.9), 25.2 (1.9-180.9), and 83.6 (8.7-134.4) in serum, and 78.2 (35.9-184), 272.3 (122-641), and 744.4 (208.6-2556) in breast cancer tissue, respectively. Tamoxifen levels followed a dose-concentration relationship. The concentrations of tamoxifen and metabolites were related to each other. Serum and tissue concentrations of tamoxifen were associated with corresponding changes of SHBG levels, whereas changes of Ki-67 levels were not related. CONCLUSIONS: Estrogen agonistic effects of tamoxifen on SHBG decreased with lower dosage, whereas tamoxifen effects on Ki-67 expression did not change. This together with a >10-fold variation in serum tamoxifen concentrations and a serum to tissue concentration relationship suggest that tamoxifen treatment may be improved by administration of lower doses and therapeutic drug monitoring.[1]

References

Tamoxifen and metabolite concentrations in serum and breast cancer tissue during three dose regimens in a randomized preoperative trial. Kisanga, E.R., Gjerde, J., Guerrieri-Gonzaga, A., Pigatto, F., Pesci-Feltri, A., Robertson, C., Serrano, D., Pelosi, G., Decensi, A., Lien, E.A. Clin. Cancer Res. (2004) [Pubmed]

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