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Open Access 01-06-2020 | Breast Cancer | Original Article

Exposure–response analysis of endoxifen serum concentrations in early-breast cancer

Authors: Anabel Beatriz Sanchez-Spitman, Dirk-Jan A. R. Moes, Jesse J. Swen, Vincent O. Dezentjé, Diether Lambrechts, Patrick Neven, Hans Gelderblom, Henk-Jan Guchelaar

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2020

Abstract

Purpose

Tamoxifen is part of endocrine therapy in breast cancer treatment. Studies have indicated the use of endoxifen concentrations, tamoxifen active metabolite, to guide tamoxifen efficacy. Three endoxifen thresholds have been suggested (5.9 ng/ml, 5.2 ng/ml and 3.3 ng/ml) for therapeutic drug monitoring (TDM). Our aim was to validate these thresholds and to examine endoxifen exposure with clinical outcome in early-breast cancer patients using tamoxifen.

Methods

Data from 667 patients from the CYPTAM study (NTR1509) were available. Patients were stratified (above or below), according to the endoxifen threshold values for tamoxifen efficacy and tested by Cox regression. Logistic regressions to estimate the probability of relapse and tamoxifen discontinuation were performed.

Results

None of the thresholds showed a statistically significant difference in relapse-free survival: 5.2 ng/ml threshold: hazard ratio (HR): 2.545, 95% confidence interval (CI) 0.912–7.096, p value: 0.074; 3.3 ng/ml threshold: HR: 0.728; 95% CI 0.421–1.258, p value: 0.255. Logistic regression did not show a statistically significant association between the risk of relapse (odds ratio (OR): 0.971 (95% CI 0.923–1.021, p value: 0.248) and the risk for tamoxifen discontinuation (OR: 1.006 95% CI 0.961–1.053, p value: 0.798) with endoxifen concentrations.

Conclusion

Our findings do not confirm the endoxifen threshold values for TDM nor does it allow definition of a novel threshold. These findings indicate a limited value of TDM to guide tamoxifen efficacy.

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Title: Exposure–response analysis of endoxifen serum concentrations in early-breast cancer
Authors: Anabel Beatriz Sanchez-Spitman
Dirk-Jan A. R. Moes
Jesse J. Swen
Vincent O. Dezentjé
Diether Lambrechts
Patrick Neven
Hans Gelderblom
Henk-Jan Guchelaar
Publication date: 01-06-2020
Publisher: Springer Berlin Heidelberg
Keywords: Breast Cancer
Breast Cancer
Tamoxifen
Published in: Cancer Chemotherapy and Pharmacology / Issue 6/2020
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-020-04089-x

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