CYP2D6 genotype and outcome in tamoxifen treated early breast cancer
Background and purpose: The clinical significance of individual CYP2D6 activity for the outcome of tamoxifen treatment in early breast cancer is unclear. Our previous investigation in patients diagnosed over the period 1998–2000 indicated an association between reduced CYP2D6 activity and poor outco...
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Medical Journals Sweden
2025-07-01
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| Series: | Acta Oncologica |
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| Online Access: | https://medicaljournalssweden.se/actaoncologica/article/view/43208 |
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| author | Linda Thorén Jonatan D. Lindh Espen Molden Marianne Kristiansen Kringen Jonas Bergh Erik Eliasson Sara Margolin |
| author_facet | Linda Thorén Jonatan D. Lindh Espen Molden Marianne Kristiansen Kringen Jonas Bergh Erik Eliasson Sara Margolin |
| author_sort | Linda Thorén |
| collection | DOAJ |
| description | Background and purpose: The clinical significance of individual CYP2D6 activity for the outcome of tamoxifen treatment in early breast cancer is unclear. Our previous investigation in patients diagnosed over the period 1998–2000 indicated an association between reduced CYP2D6 activity and poor outcome in premenopausal women. The aim of this study was to investigate the association between CYP2D6 genotype and clinical outcome in a larger tamoxifen treated cohort.
Patients/material and methods: Swedish breast cancer patients who initiated adjuvant tamoxifen treatment over the period 2006–2014 constituted the full study cohort. Clinical information was collected from medical records. Data on endocrine treatment, use of CYP2D6 inhibitors was retrieved from the Swedish Prescribed Drug Register. CYP2D6 was genotyped and translated into predicted metabolic activity. The association between CYP2D6 activity and clinical outcome was analyzed using Cox regression, controlling for potential confounding variables. Subgroup analyses were performed based on menopausal status, tamoxifen treatment for at least 1 year and as single endocrine treatment, HER2-status and tamoxifen monotherapy.
Results: A total of 1,103 patients were included. A total of 761 patients received tamoxifen as monotherapy. A total of 42% were premenopausal. Median follow-up was 11.4 years. No significant association was found between CYP2D6 activity and recurrence (adjusted hazard ratio [aHR] 1.18, 95% CI 0.92; 1.52) or breast cancer mortality (aHR 1.41, 95%CI 0.93; 2.13) in the full cohort, or in the subgroup with tamoxifen monotherapy (aHR 1.39, CI 0.99; 1.96 and 1.88, CI 0.98; 3.60 respectively).
Interpretation: No association was noted between reduced CYP2D6 activity and poorer outcome in this early breast cancer cohort, with patients generally at lower risk of recurrence, reflecting the role of adjuvant tamoxifen in current clinical practice.
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| format | Article |
| id | doaj-art-69c25f094f864878beb2d13409a255c6 |
| institution | Kabale University |
| issn | 1651-226X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Medical Journals Sweden |
| record_format | Article |
| series | Acta Oncologica |
| spelling | doaj-art-69c25f094f864878beb2d13409a255c62025-08-20T03:28:41ZengMedical Journals SwedenActa Oncologica1651-226X2025-07-016410.2340/1651-226X.2025.43208CYP2D6 genotype and outcome in tamoxifen treated early breast cancerLinda Thorén0https://orcid.org/0000-0003-1541-6191Jonatan D. Lindh1https://orcid.org/0000-0001-7198-7269Espen Molden2https://orcid.org/0000-0001-6190-2751Marianne Kristiansen Kringen3https://orcid.org/0000-0002-4760-1693Jonas Bergh4https://orcid.org/0000-0001-5526-1847Erik Eliasson5https://orcid.org/0000-0002-4707-4256Sara Margolin6https://orcid.org/0000-0002-5526-5570Department of Clinical Science and Education at Södersjukhuset, Karolinska Institutet, Stockholm, Sweden; Department of Oncology, Södersjukhuset, Stockholm, SwedenDepartment of Laboratory Medicine, Clinical Pharmacology, Karolinska Institutet and Medical Diagnostics, Karolinska University Hospital, Stockholm, SwedenCenter for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway; Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, NorwayCenter for Psychopharmacology, Diakonhjemmet Hospital, Oslo and Department of Life Sciences and Health, Oslo Metropolitan University, Oslo, NorwayDepartment of Oncology-Pathology, Karolinska Institutet, Breast Cancer Center Karolinska Comprehensive Cancer Center, Karolinska University Hospital, Stockholm, SwedenDepartment of Laboratory Medicine, Clinical Pharmacology, Karolinska Institutet and Medical Diagnostics, Karolinska University Hospital, Stockholm, SwedenDepartment of Clinical Science and Education at Södersjukhuset, Karolinska Institutet and Department of Oncology, Södersjukhuset, Stockholm, SwedenBackground and purpose: The clinical significance of individual CYP2D6 activity for the outcome of tamoxifen treatment in early breast cancer is unclear. Our previous investigation in patients diagnosed over the period 1998–2000 indicated an association between reduced CYP2D6 activity and poor outcome in premenopausal women. The aim of this study was to investigate the association between CYP2D6 genotype and clinical outcome in a larger tamoxifen treated cohort. Patients/material and methods: Swedish breast cancer patients who initiated adjuvant tamoxifen treatment over the period 2006–2014 constituted the full study cohort. Clinical information was collected from medical records. Data on endocrine treatment, use of CYP2D6 inhibitors was retrieved from the Swedish Prescribed Drug Register. CYP2D6 was genotyped and translated into predicted metabolic activity. The association between CYP2D6 activity and clinical outcome was analyzed using Cox regression, controlling for potential confounding variables. Subgroup analyses were performed based on menopausal status, tamoxifen treatment for at least 1 year and as single endocrine treatment, HER2-status and tamoxifen monotherapy. Results: A total of 1,103 patients were included. A total of 761 patients received tamoxifen as monotherapy. A total of 42% were premenopausal. Median follow-up was 11.4 years. No significant association was found between CYP2D6 activity and recurrence (adjusted hazard ratio [aHR] 1.18, 95% CI 0.92; 1.52) or breast cancer mortality (aHR 1.41, 95%CI 0.93; 2.13) in the full cohort, or in the subgroup with tamoxifen monotherapy (aHR 1.39, CI 0.99; 1.96 and 1.88, CI 0.98; 3.60 respectively). Interpretation: No association was noted between reduced CYP2D6 activity and poorer outcome in this early breast cancer cohort, with patients generally at lower risk of recurrence, reflecting the role of adjuvant tamoxifen in current clinical practice. https://medicaljournalssweden.se/actaoncologica/article/view/43208CYP2D6tamoxifenbreast canceradjuvant therapybioactivationmenopausal status |
| spellingShingle | Linda Thorén Jonatan D. Lindh Espen Molden Marianne Kristiansen Kringen Jonas Bergh Erik Eliasson Sara Margolin CYP2D6 genotype and outcome in tamoxifen treated early breast cancer Acta Oncologica CYP2D6 tamoxifen breast cancer adjuvant therapy bioactivation menopausal status |
| title | CYP2D6 genotype and outcome in tamoxifen treated early breast cancer |
| title_full | CYP2D6 genotype and outcome in tamoxifen treated early breast cancer |
| title_fullStr | CYP2D6 genotype and outcome in tamoxifen treated early breast cancer |
| title_full_unstemmed | CYP2D6 genotype and outcome in tamoxifen treated early breast cancer |
| title_short | CYP2D6 genotype and outcome in tamoxifen treated early breast cancer |
| title_sort | cyp2d6 genotype and outcome in tamoxifen treated early breast cancer |
| topic | CYP2D6 tamoxifen breast cancer adjuvant therapy bioactivation menopausal status |
| url | https://medicaljournalssweden.se/actaoncologica/article/view/43208 |
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