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

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 unidentif...

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Bibliographic Details
Published in:Breast cancer research and treatment 2019-08, Vol.177 (1), p.185-195
Main Authors: Helland, Thomas, Hagen, Kari Britt, Haugstøyl, Martha Eimstad, Kvaløy, Jan Terje, Lunde, Siri, Lode, Kirsten, Lind, Ragna Anne, Gripsrud, Birgitta Haga, Jonsdottir, Kristin, Gjerde, Jennifer, Bifulco, Ersilia, Hustad, Steinar, Jonassen, Janne, Aas, Turid, Lende, Tone Hoel, Lien, Ernst Asbjørn, Janssen, Emiel Adrianus Maria, Søiland, Håvard, Mellgren, Gunnar
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Analysis
Antineoplastic Agents, Hormonal - adverse effects
Antineoplastic Agents, Hormonal - pharmacokinetics
Antineoplastic Agents, Hormonal - therapeutic use
Biomarkers
Breast cancer
Breast Neoplasms - complications
Breast Neoplasms - diagnosis
Breast Neoplasms - drug therapy
Breast Neoplasms - epidemiology
Cancer
Cancer research
Cancer therapies
Chemotherapy
Chromatography, Liquid
Drug Monitoring
Drugstores
Endocrine therapy
Epidemiology
Female
Health aspects
Health risk assessment
Hormone replacement therapy
Humans
Medication Adherence
Medicine
Medicine & Public Health
Metabolites
Middle Aged
Nausea
Oncology
Patient Reported Outcome Measures
Pharmacy
Population studies
Prognosis
Regression analysis
Risk factors
Side effects
Surveys and Questionnaires
Tamoxifen
Tamoxifen - adverse effects
Tamoxifen - pharmacokinetics
Tamoxifen - therapeutic use
Tandem Mass Spectrometry
Therapeutic drug monitoring
Vagina
Vagina - drug effects
Vagina - physiopathology
Young Adult
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Summary: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.
ISSN:0167-6806
1573-7217
DOI:10.1007/s10549-019-05294-w