Low Z-4OHtam concentrations are associated with adverse clinical outcome among early stage premenopausal breast cancer patients treated with adjuvant tamoxifen
| العنوان: | Low Z-4OHtam concentrations are associated with adverse clinical outcome among early stage premenopausal breast cancer patients treated with adjuvant tamoxifen |
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| المؤلفون: | Steinar Hustad, Marit Synnestvedt, Jan Terje Kvaløy, Daniel L. Hertz, Anna Barbro Sætersdal, Gunnar Mellgren, Bjørnar Gilje, Elin Borgen, Ingvil Mjaaland, Håvard Søiland, Egil S. Blix, Emiel A. M. Janssen, Tone Hoel Lende, Kjetil Weyde, Gro Wiedswang, Bjørn Naume, Ersilia Bifulco, Thomas Helland |
| المصدر: | Molecular Oncology Molecular Oncology, Vol 15, Iss 4, Pp 957-967 (2021) |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Oncology, Cancer Research, Metabolite, outcomes, chemistry.chemical_compound, 0302 clinical medicine, Stage (cooking), skin and connective tissue diseases, Research Articles, medicine.diagnostic_test, Norway, General Medicine, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Treatment Outcome, 4OHtam, 030220 oncology & carcinogenesis, Cohort, Molecular Medicine, Female, hormones, hormone substitutes, and hormone antagonists, medicine.drug, Research Article, Adult, medicine.medical_specialty, Antineoplastic Agents, Hormonal, medicine.drug_class, therapeutic drug monitoring, Breast Neoplasms, lcsh:RC254-282, 03 medical and health sciences, Breast cancer, Medisinske Fag: 700 [VDP], Internal medicine, Genetics, medicine, Humans, VDP::Medisinske Fag: 700, Active metabolite, Retrospective Studies, concentration threshold, business.industry, medicine.disease, VDP::Medical disciplines: 700, Tamoxifen, 030104 developmental biology, chemistry, Premenopause, Estrogen, Therapeutic drug monitoring, endoxifen, business |
| الوصف: | Concentrations of active tamoxifen metabolites may be predictive of tamoxifen efficacy, and several therapeutic thresholds have been reported. This study of 406 ER+ breast cancer patients replicated an association between a previously reported active tamoxifen threshold (Z‐4OHtam ≤ 3.26 nm) and adverse BC outcome. The association was identified in early‐stage premenopausal patients using tamoxifen alone without sequential aromatase inhibitor use. Low steady‐state levels of active tamoxifen metabolites have been associated with inferior treatment outcomes. In this retrospective analysis of 406 estrogen receptor‐positive breast cancer (BC) patients receiving adjuvant tamoxifen as initial treatment, we have associated our previously reported thresholds for the two active metabolites, Z‐endoxifen and Z‐4‐hydroxy‐tamoxifen (Z‐4OHtam), with treatment outcomes in an independent cohort of BC patients. Among all patients, metabolite levels did not affect survival. However, in the premenopausal subgroup receiving tamoxifen alone (n = 191) we confirmed an inferior BC ‐specific survival in patients with the previously described serum concentration threshold of Z‐4OHtam ≤ 3.26 nm (HR = 2.37, 95% CI = 1.02–5.48, P = 0.039). The ‘dose–response’ survival trend in patients categorized to ordinal concentration cut‐points of Z‐4OHtamoxifen (≤ 3.26, 3.27–8.13, > 8.13 nm) was also replicated (P‐trend log‐rank = 0.048). Z‐endoxifen was not associated with outcome. This is the first study to confirm the association between a published active tamoxifen metabolite threshold and BC outcome in an independent patient cohort. Premenopausal patients receiving 5‐year of tamoxifen alone may benefit from therapeutic drug monitoring to ensure tamoxifen effectiveness. |
| وصف الملف: | application/pdf |
| تدمد: | 1878-0261 1574-7891 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::243949774badb71683ce2b2d125a5556 https://pubmed.ncbi.nlm.nih.gov/33252186 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....243949774badb71683ce2b2d125a5556 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18780261 15747891 |
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