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CYP2D6 genotype pre...
CYP2D6 genotype predicts tamoxifen discontinuation and drug response : a secondary analysis of the KARISMA trial
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- He, W. (författare)
- Karolinska Institutet,Karolinska Institute,Zhejiang University
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- Eriksson, M. (författare)
- Karolinska Institutet,Karolinska Institute
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- Eliasson, E. (författare)
- Karolinska Institutet
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- Grassmann, F. (författare)
- Karolinska Institutet,Karolinska Institute,University of Aberdeen
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- Bäcklund, M. (författare)
- Karolinska Institutet,Karolinska Institute
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- Gabrielson, M. (författare)
- Karolinska Institutet,Karolinska Institute
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- Hammarström, M. (författare)
- Karolinska Institutet,Karolinska Institute
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- Margolin, S. (författare)
- Karolinska Institutet,Karolinska Institute,Stockholm South General Hospital
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- Thorén, L. (författare)
- Karolinska Institutet,Karolinska Institute,Stockholm South General Hospital
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- Wengström, Y. (författare)
- Karolinska Institutet
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- Borgquist, S. (författare)
- Lund University,Lunds universitet,Bröstcancer - prevention & intervention,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Bröstcancer,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breast cancer prevention & intervention,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Breastcancer,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital,Aarhus University Hospital
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- Hall, P. (författare)
- Karolinska Institutet,Karolinska Institute,Stockholm South General Hospital
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- Czene, K. (författare)
- Karolinska Institutet,Karolinska Institute
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(creator_code:org_t)
- Elsevier BV, 2021
- 2021
- Engelska.
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 32:10, s. 1286-1293
- Relaterad länk:
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http://dx.doi.org/10... (free)
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Abstract
Ämnesord
Stäng
- Background: Guidelines regarding whether tamoxifen should be prescribed based on women's cytochrome P450 2D6 (CYP2D6) genotypes are conflicting and have caused confusion. This study aims to investigate if CYP2D6 metabolizer status isa associated with tamoxifen-related endocrine symptoms, tamoxifen discontinuation, and mammographic density change. Patients and methods: We used data from 1440 healthy women who participated the KARISMA dose determination trial. Endocrine symptoms were measured using a modified Functional Assessment of Cancer Therapy – Endocrine Symptoms (FACT-ES) questionnaire. Change in mammographic density was measured and used as a proxy for tamoxifen response. Participants were genotyped and categorized as poor, intermediate, normal, or ultrarapid CYP2D6 metabolizers. Results: The median endoxifen level per mg oral tamoxifen among poor, intermediate, normal and ultrarapid CYP2D6 metabolizers were 0.18 ng/ml, 0.38 ng/ml, 0.56 ng/ml and 0.67 ng/ml, respectively. Ultrarapid CYP2D6 metabolizers were more likely than other groups to report a clinically relevant change in cold sweats, hot flash, mood swings, being irritable, as well as the overall modified FACT-ES score, after taking tamoxifen. The 6-month tamoxifen discontinuation rates among poor, intermediate, normal, and ultrarapid CYP2D6 metabolizers were 25.7%, 23.6%, 28.6%, and 44.4%, respectively. Among those who continued and finished the 6-month tamoxifen intervention, the mean change in dense area among poor, intermediate, normal, and ultrarapid CYP2D6 metabolizers were −0.8 cm2, −4.5 cm2, −4.1 cm2, and −8.0 cm2 respectively. Conclusions: Poor CYP2D6 metabolizers are likely to experience an impaired response to tamoxifen, measured through mammographic density reduction. In contrast, ultrarapid CYP2D6 metabolizers are at risk for exaggerated response with pronounced adverse effects that may lead to treatment discontinuation.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- breast cancer
- CYP2D6 genotype
- mammographic density
- tamoxifen
- treatment discontinuation
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
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He, W.
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Eriksson, M.
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Eliasson, E.
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Grassmann, F.
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Bäcklund, M.
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Gabrielson, M.
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visa fler...
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Hammarström, M.
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Margolin, S.
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Thorén, L.
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Wengström, Y.
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Borgquist, S.
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Hall, P.
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Czene, K.
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Cancer och onkol ...
- Artiklar i publikationen
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Annals of Oncolo ...
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Annals of oncolo ...
- Av lärosätet
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Lunds universitet
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Karolinska Institutet