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No association found between CYP2D6 genotype and early breast cancer events in tamoxifen-treated patients.

Markkula, Andrea LU ; Hjertberg, Maria; Rose, Carsten LU ; Ingvar, Christian LU and Jernström, Helena LU (2014) In Acta Oncologica 53(2). p.195-200
Abstract
Background. CYP2D6 is considered the key enzyme in tamoxifen metabolism. Several studies have investigated the relationship between the CYP2D6 genotype and tamoxifen treatment outcome, with discrepant results. CYP2D6 inhibitor use, aromatase inhibitor use, and chemotherapy may account for some of the discrepancies. We examined the association between CYP2D6 genotype and early breast cancer events in tamoxifen-treated breast cancer patients, in relation to CYP2D6 inhibitor use, aromatase inhibitor use, and chemotherapy. Material and methods. Pre- and postoperative questionnaires on lifestyle and concomitant medications were completed by 634 primary breast cancer patients between 2002 and 2008, among whom 333 patients had ER-positive tumors... (More)
Background. CYP2D6 is considered the key enzyme in tamoxifen metabolism. Several studies have investigated the relationship between the CYP2D6 genotype and tamoxifen treatment outcome, with discrepant results. CYP2D6 inhibitor use, aromatase inhibitor use, and chemotherapy may account for some of the discrepancies. We examined the association between CYP2D6 genotype and early breast cancer events in tamoxifen-treated breast cancer patients, in relation to CYP2D6 inhibitor use, aromatase inhibitor use, and chemotherapy. Material and methods. Pre- and postoperative questionnaires on lifestyle and concomitant medications were completed by 634 primary breast cancer patients between 2002 and 2008, among whom 333 patients had ER-positive tumors and received tamoxifen. CYP2D6*3, *4, *6, *10 and *41 were genotyped. Information on clinical data, breast cancer events, and tumor characteristics was obtained from patients' charts, population registries, the Regional Tumor Registry, and pathology reports. Results. Median follow-up was 4.9 years. Neither poor metabolizers (adjusted HR 0.50; 95% CI 0.07-3.82) nor intermediate metabolizers (adjusted HR 1.00; 95% CI 0.47-2.11) had an increased risk of early breast cancer events when compared with extensive metabolizers. CYP2D6 activity score (taking into account genotype and CYP2D6 inhibitor use) was not associated with early breast cancer events (LogRank, Ptrend = 0.44). Conclusions. CYP2D6 genotype was not associated with tamoxifen treatment outcome, even when CYP2D6 inhibitor use, aromatase inhibitor use, or chemotherapy was taken into account. CYP2D6 genotype may be of minor importance for tamoxifen-treated patients in Scandinavia. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Acta Oncologica
volume
53
issue
2
pages
195 - 200
publisher
Taylor & Francis
external identifiers
  • wos:000329522000005
  • pmid:24125101
  • scopus:84892183086
ISSN
1651-226X
DOI
10.3109/0284186X.2013.840739
language
English
LU publication?
yes
id
22f982db-b806-44ce-8dd6-8c4d2f8def1d (old id 4143259)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24125101?dopt=Abstract
date added to LUP
2013-11-05 00:18:11
date last changed
2017-08-27 03:11:43
@article{22f982db-b806-44ce-8dd6-8c4d2f8def1d,
  abstract     = {Background. CYP2D6 is considered the key enzyme in tamoxifen metabolism. Several studies have investigated the relationship between the CYP2D6 genotype and tamoxifen treatment outcome, with discrepant results. CYP2D6 inhibitor use, aromatase inhibitor use, and chemotherapy may account for some of the discrepancies. We examined the association between CYP2D6 genotype and early breast cancer events in tamoxifen-treated breast cancer patients, in relation to CYP2D6 inhibitor use, aromatase inhibitor use, and chemotherapy. Material and methods. Pre- and postoperative questionnaires on lifestyle and concomitant medications were completed by 634 primary breast cancer patients between 2002 and 2008, among whom 333 patients had ER-positive tumors and received tamoxifen. CYP2D6*3, *4, *6, *10 and *41 were genotyped. Information on clinical data, breast cancer events, and tumor characteristics was obtained from patients' charts, population registries, the Regional Tumor Registry, and pathology reports. Results. Median follow-up was 4.9 years. Neither poor metabolizers (adjusted HR 0.50; 95% CI 0.07-3.82) nor intermediate metabolizers (adjusted HR 1.00; 95% CI 0.47-2.11) had an increased risk of early breast cancer events when compared with extensive metabolizers. CYP2D6 activity score (taking into account genotype and CYP2D6 inhibitor use) was not associated with early breast cancer events (LogRank, Ptrend = 0.44). Conclusions. CYP2D6 genotype was not associated with tamoxifen treatment outcome, even when CYP2D6 inhibitor use, aromatase inhibitor use, or chemotherapy was taken into account. CYP2D6 genotype may be of minor importance for tamoxifen-treated patients in Scandinavia.},
  author       = {Markkula, Andrea and Hjertberg, Maria and Rose, Carsten and Ingvar, Christian and Jernström, Helena},
  issn         = {1651-226X},
  language     = {eng},
  number       = {2},
  pages        = {195--200},
  publisher    = {Taylor & Francis},
  series       = {Acta Oncologica},
  title        = {No association found between CYP2D6 genotype and early breast cancer events in tamoxifen-treated patients.},
  url          = {http://dx.doi.org/10.3109/0284186X.2013.840739},
  volume       = {53},
  year         = {2014},
}