Drug monitoring of tamoxifen metabolites predicts vaginal dryness and verifies a low discontinuation rate from the Norwegian Prescription Database.
Adult
Aged
Aged, 80 and over
Antineoplastic Agents, Hormonal
/ adverse effects
Biomarkers
Breast Neoplasms
/ complications
Chromatography, Liquid
Drug Monitoring
Female
Humans
Medication Adherence
Middle Aged
Patient Reported Outcome Measures
Prognosis
Surveys and Questionnaires
Tamoxifen
/ adverse effects
Tandem Mass Spectrometry
Vagina
/ drug effects
Young Adult
Adherence
Discontinuation
Endocrine therapy
Metabolism
Side effects
Tamoxifen
Journal
Breast cancer research and treatment
ISSN: 1573-7217
Titre abrégé: Breast Cancer Res Treat
Pays: Netherlands
ID NLM: 8111104
Informations de publication
Date de publication:
Aug 2019
Aug 2019
Historique:
received:
16
05
2019
accepted:
22
05
2019
pubmed:
31
5
2019
medline:
21
12
2019
entrez:
31
5
2019
Statut:
ppublish
Résumé
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. 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. 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. 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.
Identifiants
pubmed: 31144152
doi: 10.1007/s10549-019-05294-w
pii: 10.1007/s10549-019-05294-w
doi:
Substances chimiques
Antineoplastic Agents, Hormonal
0
Biomarkers
0
Tamoxifen
094ZI81Y45
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
185-195Subventions
Organisme : Western Norway Health Authority
ID : F-11314
Organisme : Western Norway Health Authority
ID : 507074
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