Skip to main content
Erschienen in: Breast Cancer Research and Treatment 1/2019

29.05.2019 | Epidemiology

Drug monitoring of tamoxifen metabolites predicts vaginal dryness and verifies a low discontinuation rate from the Norwegian Prescription Database

verfasst von: Thomas Helland, Kari Britt Hagen, Martha Eimstad Haugstøyl, Jan Terje Kvaløy, Siri Lunde, Kirsten Lode, Ragna Anne Lind, Birgitta Haga Gripsrud, Kristin Jonsdottir, Jennifer Gjerde, Ersilia Bifulco, Steinar Hustad, Janne Jonassen, Turid Aas, Tone Hoel Lende, Ernst Asbjørn Lien, Emiel Adrianus Maria Janssen, Håvard Søiland, Gunnar Mellgren

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 1/2019

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Tamoxifen is an important targeted endocrine therapy in breast cancer. However, side effects and early discontinuation of tamoxifen remains a barrier for obtaining the improved outcome benefits of long-term tamoxifen treatment. Biomarkers predictive of tamoxifen side effects remain unidentified. The objective of this prospective population-based study was to investigate the value of tamoxifen metabolite concentrations as biomarkers for side effects. A second objective was to assess the validity of discontinuation rates obtained through pharmacy records with the use of tamoxifen drug monitoring.

Methods

Longitudinal serum samples, patient-reported outcome measures and pharmacy records from 220 breast cancer patients were obtained over a 6-year period. Serum concentrations of tamoxifen metabolites were measured by LC–MS/MS. Associations between metabolite concentrations and side effects were analyzed by logistic regression and cross table analyses. To determine the validity of pharmacy records we compared longitudinal tamoxifen concentrations to discontinuation rates obtained through the Norwegian Prescription database (NorPD). Multivariable Cox regression models were performed to identify predictors of discontinuation.

Results

At the 2nd year of follow-up, a significant association between vaginal dryness and high concentrations of tamoxifen, Z-4′-OHtam and tam-NoX was identified. NorPD showed a tamoxifen-discontinuation rate of 17.9% at 5 years and drug monitoring demonstrated similar rates. Nausea, vaginal dryness and chemotherapy-naive status were significant risk factors for tamoxifen discontinuation.

Conclusions

This real-world data study suggests that measurements of tamoxifen metabolite concentrations may be predictive of vaginal dryness in breast cancer patients and verifies NorPD as a reliable source of adherence data.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
3.
Zurück zum Zitat Davies C, Pan H, Godwin J, Gray R, Arriagada R et al (2013) Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet 381(9869):805–816CrossRef Davies C, Pan H, Godwin J, Gray R, Arriagada R et al (2013) Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet 381(9869):805–816CrossRef
13.
Zurück zum Zitat Coller JK, Krebsfaenger N, Klein K, Endrizzi K, Wolbold R et al (2002) The influence of CYP2B6, CYP2C9 and CYP2D6 genotypes on the formation of the potent antioestrogen Z-4-hydroxy-tamoxifen in human liver. Br J Clin Pharmacol 54(2):157–167CrossRef Coller JK, Krebsfaenger N, Klein K, Endrizzi K, Wolbold R et al (2002) The influence of CYP2B6, CYP2C9 and CYP2D6 genotypes on the formation of the potent antioestrogen Z-4-hydroxy-tamoxifen in human liver. Br J Clin Pharmacol 54(2):157–167CrossRef
19.
Zurück zum Zitat Jager NG, Linn SC, Schellens JH, Beijnen JH (2015) Tailored tamoxifen treatment for breast cancer patients: a perspective. Clin Breast Cancer 15(4):241–244CrossRef Jager NG, Linn SC, Schellens JH, Beijnen JH (2015) Tailored tamoxifen treatment for breast cancer patients: a perspective. Clin Breast Cancer 15(4):241–244CrossRef
20.
Zurück zum Zitat Barginear MF, Jaremko M, Peter I, Yu C, Kasai Y et al (2011) Increasing tamoxifen dose in breast cancer patients based on CYP2D6 genotypes and endoxifen levels: effect on active metabolite isomers and the antiestrogenic activity score. Clin Pharmacol Therap 90(4):605–611. https://doi.org/10.1038/clpt.2011.153 CrossRef Barginear MF, Jaremko M, Peter I, Yu C, Kasai Y et al (2011) Increasing tamoxifen dose in breast cancer patients based on CYP2D6 genotypes and endoxifen levels: effect on active metabolite isomers and the antiestrogenic activity score. Clin Pharmacol Therap 90(4):605–611. https://​doi.​org/​10.​1038/​clpt.​2011.​153 CrossRef
22.
Zurück zum Zitat Goetz MP, Suman VJ, Reid JM, Northfelt DW, Mahr MA et al (2017) First-in-human phase I study of the tamoxifen metabolite Z-endoxifen in women with endocrine-refractory metastatic breast cancer. J Clin Oncol 2017(2073):3246 Goetz MP, Suman VJ, Reid JM, Northfelt DW, Mahr MA et al (2017) First-in-human phase I study of the tamoxifen metabolite Z-endoxifen in women with endocrine-refractory metastatic breast cancer. J Clin Oncol 2017(2073):3246
26.
Zurück zum Zitat Fallowfield LJ, Leaity SK, Howell A, Benson S, Cella D (1999) Assessment of quality of life in women undergoing hormonal therapy for breast cancer: validation of an endocrine symptom subscale for the FACT-B. Breast Cancer Res Treat 55(2):189–199CrossRef Fallowfield LJ, Leaity SK, Howell A, Benson S, Cella D (1999) Assessment of quality of life in women undergoing hormonal therapy for breast cancer: validation of an endocrine symptom subscale for the FACT-B. Breast Cancer Res Treat 55(2):189–199CrossRef
30.
Zurück zum Zitat NBCG (2017) National action plan with guidelines for diagnosis, treatment and follow up of breast cancer patients. vol IS-2669. Norwegian Directory of Health, www.helsedirektoratet.no NBCG (2017) National action plan with guidelines for diagnosis, treatment and follow up of breast cancer patients. vol IS-2669. Norwegian Directory of Health, www.​helsedirektorate​t.​no
36.
Zurück zum Zitat Suwalsky M, Hernandez P, Villena F, Aguilar F, Sotomayor CP (1998) Interaction of the anticancer drug tamoxifen with the human erythrocyte membrane and molecular models. Zeitschrift fur Naturforschung C. J Biosci 53(3–4):182–190 Suwalsky M, Hernandez P, Villena F, Aguilar F, Sotomayor CP (1998) Interaction of the anticancer drug tamoxifen with the human erythrocyte membrane and molecular models. Zeitschrift fur Naturforschung C. J Biosci 53(3–4):182–190
Metadaten
Titel
Drug monitoring of tamoxifen metabolites predicts vaginal dryness and verifies a low discontinuation rate from the Norwegian Prescription Database
verfasst von
Thomas Helland
Kari Britt Hagen
Martha Eimstad Haugstøyl
Jan Terje Kvaløy
Siri Lunde
Kirsten Lode
Ragna Anne Lind
Birgitta Haga Gripsrud
Kristin Jonsdottir
Jennifer Gjerde
Ersilia Bifulco
Steinar Hustad
Janne Jonassen
Turid Aas
Tone Hoel Lende
Ernst Asbjørn Lien
Emiel Adrianus Maria Janssen
Håvard Søiland
Gunnar Mellgren
Publikationsdatum
29.05.2019
Verlag
Springer US
Erschienen in
Breast Cancer Research and Treatment / Ausgabe 1/2019
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-019-05294-w

Weitere Artikel der Ausgabe 1/2019

Breast Cancer Research and Treatment 1/2019 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.