Early increase in tamoxifen dose in CYP2D6 poor metaboliser breast cancer patients and survival: A propensity score matching analysis
Purpose: Tamoxifen is a drug used for hormone receptor-positive breast cancers, primarily metabolised by the CYP2D6 enzyme into active metabolites such as endoxifen. CYP2D6 displays varying degrees of activity depending on its genotype. This study aims to analyse the effect of an early increase in t...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | Breast |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0960977623004290 |
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| author | Isabel Blancas Marina Linares-Rodríguez Eduardo Martínez de Dueñas Carmen Herrero-Vicent María D. Molero-Mir José M. Garrido Fernando Rodríguez-Serrano |
| author_facet | Isabel Blancas Marina Linares-Rodríguez Eduardo Martínez de Dueñas Carmen Herrero-Vicent María D. Molero-Mir José M. Garrido Fernando Rodríguez-Serrano |
| author_sort | Isabel Blancas |
| collection | DOAJ |
| description | Purpose: Tamoxifen is a drug used for hormone receptor-positive breast cancers, primarily metabolised by the CYP2D6 enzyme into active metabolites such as endoxifen. CYP2D6 displays varying degrees of activity depending on its genotype. This study aims to analyse the effect of an early increase in tamoxifen dose in poor metabolisers (PM) on survival. Methods: We enrolled 220 patients diagnosed with breast cancer who were treated with tamoxifen. CYP2D6 polymorphisms were determined, and the phenotype was estimated according to the Clinical Pharmacogenetics Implementation Consortium. Disease-free survival (DFS) and overall survival (OS) were analysed considering the entire patient group, and a subgroup of 110 patients selected by Propensity Score Matching (PSM). All women were treated with 20 mg/day of tamoxifen for 5 years, except PM, who initially received 20 mg/day for 4 months, followed by 40 mg/day for 4 months and 60 mg/day for 4 months before returning to the standard dose of 20 mg/day until completing 5 years of treatment. Results: The analysis of the influence of CYP2D6 polymorphisms in the complete group and in the PSM subgroup revealed no significant differences for DFS or OS. Furthermore, DFS and OS were analysed in relation to various covariates such as age, histological grade, nodal status, tumour size, HER-2, Ki-67, chemotherapy, and radiotherapy. Only age, histological grade, nodal status, and chemotherapy treatment demonstrated statistical significance. Conclusion: An early increase in tamoxifen dose in PM patients is not associated with survival differences among CYP2D6 phenotypes. |
| first_indexed | 2024-03-13T05:41:03Z |
| format | Article |
| id | doaj.art-cdceef7176544ad684c909757b5998d3 |
| institution | Directory Open Access Journal |
| issn | 1532-3080 |
| language | English |
| last_indexed | 2024-03-13T05:41:03Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Breast |
| spelling | doaj.art-cdceef7176544ad684c909757b5998d32023-06-14T04:32:41ZengElsevierBreast1532-30802023-06-0169342348Early increase in tamoxifen dose in CYP2D6 poor metaboliser breast cancer patients and survival: A propensity score matching analysisIsabel Blancas0Marina Linares-Rodríguez1Eduardo Martínez de Dueñas2Carmen Herrero-Vicent3María D. Molero-Mir4José M. Garrido5Fernando Rodríguez-Serrano6Department of Medicine, School of Medicine, University of Granada, Granada, Spain; Department of Medical Oncology, San Cecilio University Hospital, Granada, Spain; Biosanitary Research Institute of Granada (ibs.GRANADA), Granada, Spain; Corresponding author. San Cecilio University Hospital, Avenida del Conocimiento s/n, 18016, Armilla, Granada, Spain.Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, Granada, SpainDepartment of Oncology, Hospital Provincial de Castellón, Castellón, SpainDepartment of Oncology, Hospital Provincial de Castellón, Castellón, SpainDepartment of Medicine, School of Medicine, University of Granada, Granada, SpainBiosanitary Research Institute of Granada (ibs.GRANADA), Granada, Spain; Department of Surgery and Surgical Specialties, University of Granada, Granada, SpainBiosanitary Research Institute of Granada (ibs.GRANADA), Granada, Spain; Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, Granada, SpainPurpose: Tamoxifen is a drug used for hormone receptor-positive breast cancers, primarily metabolised by the CYP2D6 enzyme into active metabolites such as endoxifen. CYP2D6 displays varying degrees of activity depending on its genotype. This study aims to analyse the effect of an early increase in tamoxifen dose in poor metabolisers (PM) on survival. Methods: We enrolled 220 patients diagnosed with breast cancer who were treated with tamoxifen. CYP2D6 polymorphisms were determined, and the phenotype was estimated according to the Clinical Pharmacogenetics Implementation Consortium. Disease-free survival (DFS) and overall survival (OS) were analysed considering the entire patient group, and a subgroup of 110 patients selected by Propensity Score Matching (PSM). All women were treated with 20 mg/day of tamoxifen for 5 years, except PM, who initially received 20 mg/day for 4 months, followed by 40 mg/day for 4 months and 60 mg/day for 4 months before returning to the standard dose of 20 mg/day until completing 5 years of treatment. Results: The analysis of the influence of CYP2D6 polymorphisms in the complete group and in the PSM subgroup revealed no significant differences for DFS or OS. Furthermore, DFS and OS were analysed in relation to various covariates such as age, histological grade, nodal status, tumour size, HER-2, Ki-67, chemotherapy, and radiotherapy. Only age, histological grade, nodal status, and chemotherapy treatment demonstrated statistical significance. Conclusion: An early increase in tamoxifen dose in PM patients is not associated with survival differences among CYP2D6 phenotypes.http://www.sciencedirect.com/science/article/pii/S0960977623004290Breast cancerTamoxifenCYP2D6Disease-free survivalOverall survival |
| spellingShingle | Isabel Blancas Marina Linares-Rodríguez Eduardo Martínez de Dueñas Carmen Herrero-Vicent María D. Molero-Mir José M. Garrido Fernando Rodríguez-Serrano Early increase in tamoxifen dose in CYP2D6 poor metaboliser breast cancer patients and survival: A propensity score matching analysis Breast Breast cancer Tamoxifen CYP2D6 Disease-free survival Overall survival |
| title | Early increase in tamoxifen dose in CYP2D6 poor metaboliser breast cancer patients and survival: A propensity score matching analysis |
| title_full | Early increase in tamoxifen dose in CYP2D6 poor metaboliser breast cancer patients and survival: A propensity score matching analysis |
| title_fullStr | Early increase in tamoxifen dose in CYP2D6 poor metaboliser breast cancer patients and survival: A propensity score matching analysis |
| title_full_unstemmed | Early increase in tamoxifen dose in CYP2D6 poor metaboliser breast cancer patients and survival: A propensity score matching analysis |
| title_short | Early increase in tamoxifen dose in CYP2D6 poor metaboliser breast cancer patients and survival: A propensity score matching analysis |
| title_sort | early increase in tamoxifen dose in cyp2d6 poor metaboliser breast cancer patients and survival a propensity score matching analysis |
| topic | Breast cancer Tamoxifen CYP2D6 Disease-free survival Overall survival |
| url | http://www.sciencedirect.com/science/article/pii/S0960977623004290 |
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