Advertisement
Journal of Clinical Oncology  
Search for:
Limit by:
  Browse by Subject or Issue
Home Search or Browse JCO My JCO Subscriptions Customer Service Site Map

Journal of Clinical Oncology, Vol 25, No 25 (September 1), 2007: pp. 3837-3845
© 2007 American Society of Clinical Oncology.
DOI: 10.1200/JCO.2007.11.4850

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Save to my personal folders
Right arrow Download to citation manager
Right arrowRights & Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lim, H.-S.
Right arrow Articles by Ro, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lim, H.-S.
Right arrow Articles by Ro, J.
Related Articles
Right arrowRelated Correspondence
Social Bookmarking
 Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Clinical Implications of CYP2D6 Genotypes Predictive of Tamoxifen Pharmacokinetics in Metastatic Breast Cancer

Hyeong-Seok Lim, Han Ju Lee, Keun Seok Lee, Eun Sook Lee, In-Jin Jang, Jungsil Ro

From the Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi; and Department of Pharmacology, Seoul National University College of Medicine, Seoul, Korea

Address reprint requests to Jungsil Ro, MD, Research Institute and Hospital, National Cancer Center, 809 Madu1-dong, Ilsan-gu, Goyang-si, Gyeonggi-do, 411-769, Republic of Korea; e-mail: jungsro{at}ncc.re.kr

Purpose The CYP3A and CYP2D6 enzymes play a major role in converting tamoxifen to its active metabolites. CYP3A is a highly inducible enzyme, regulated mainly by pregnane X receptor (PXR). This study assessed the association between genetic polymorphisms of CYP2D6 and PXR, and tamoxifen pharmacokinetics (PK) and clinical outcomes in patients with breast cancer.

Patients and Methods Plasma concentrations of tamoxifen and its metabolites were measured. Common alleles of CYP2D6 and PXR were identified in 202 patients treated with tamoxifen 20 mg daily for more than 8 weeks. Twelve of the 202 patients and an additional nine patients with metastatic breast cancer receiving tamoxifen were assessed for clinical outcome in correlation with genotypes.

Results Patients carrying CYP2D6*10/*10 (n = 49) demonstrated significantly lower steady-state plasma concentrations of 4-hydroxy-N-desmethyltamoxifen and 4-hydroxytamoxifen than did those with other genotypes (n = 153; 4-hydroxy-N-desmethyltamoxifen: 7.9 v 18.9 ng/mL, P < .0001; 4-hydroxytamoxifen: 1.5 v 2.6 ng/mL, P < .0001), whereas no difference by PXR genotypes was found. CYP2D6*10/*10 was significantly more frequent among nonresponders with MBC (100% v 50%, P = .0186). In Cox proportional hazard analysis, CYP2D6 genotype and number of disease sites were significant factors affecting time to progression (TTP). The median TTP for patients receiving tamoxifen was shorter in those carrying CYP2D6*10/*10 than for others (5.0 v 21.8 months, P = .0032)

Conclusion CYP2D6*10/*10 is associated with lower steady-state plasma concentrations of active tamoxifen metabolites, which could possibly influence the clinical outcome by tamoxifen in Asian breast cancer patients.

Supported by NCC Grants No. 0410590 and 0210150.

Presented in part at the 42nd Annual Meeting of the American Society of Clinical Oncology, June 2-6, 2006, Atlanta, GA, and the 29th Annual San Antonio Breast Cancer Symposium, December 14-17, 2006, San Antonio, TX.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?

Related Correspondence

  • CYP2D6 and Ockham's Razor
    Francois Eisinger
    JCO 2008 26: 686-687 [Full Text]


This article has been cited by other articles:


Home page
JAMAHome page
W. Schroth, M. P. Goetz, U. Hamann, P. A. Fasching, M. Schmidt, S. Winter, P. Fritz, W. Simon, V. J. Suman, M. M. Ames, et al.
Association Between CYP2D6 Polymorphisms and Outcomes Among Women With Early Stage Breast Cancer Treated With Tamoxifen
JAMA, October 7, 2009; 302(13): 1429 - 1436.
[Abstract] [Full Text] [PDF]


Home page
Jpn J Clin OncolHome page
T. Toyama, H. Yamashita, H. Sugiura, N. Kondo, H. Iwase, and Y. Fujii
No Association Between CYP2D6*10 Genotype and Survival of Node-negative Japanese Breast Cancer Patients Receiving Adjuvant Tamoxifen Treatment
Jpn. J. Clin. Oncol., October 1, 2009; 39(10): 651 - 656.
[Abstract] [Full Text] [PDF]


Home page
Clin. Chem.Home page
H. Brauch, T. E. Murdter, M. Eichelbaum, and M. Schwab
Pharmacogenomics of Tamoxifen Therapy
Clin. Chem., October 1, 2009; 55(10): 1770 - 1782.
[Abstract] [Full Text] [PDF]


Home page
JCOHome page
T. L. Lash and S. R. Cole
Immortal Person-Time in Studies of Cancer Outcomes
J. Clin. Oncol., August 10, 2009; 27(23): e55 - e56.
[Full Text] [PDF]


Home page
Ann OncolHome page
T. Saeki, S. Noguchi, K. Aogi, H. Inaji, T. Tabei, and T. Ikeda
Evaluation of the safety and tolerability of oral TAS-108 in postmenopausal patients with metastatic breast cancer
Ann. Onc., May 1, 2009; 20(5): 868 - 873.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
V. O. Dezentje, H.-J. Guchelaar, J. W.R. Nortier, C. J.H. van de Velde, and H. Gelderblom
Clinical Implications of CYP2D6 Genotyping in Tamoxifen Treatment for Breast Cancer
Clin. Cancer Res., January 1, 2009; 15(1): 15 - 21.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
S.-H. Tan, S.-C. Lee, B.-C. Goh, and J. Wong
Pharmacogenetics in Breast Cancer Therapy
Clin. Cancer Res., December 15, 2008; 14(24): 8027 - 8041.
[Abstract] [Full Text] [PDF]


Home page
Drug Metab. Dispos.Home page
K. Sakuyama, T. Sasaki, S. Ujiie, K. Obata, M. Mizugaki, M. Ishikawa, and M. Hiratsuka
Functional Characterization of 17 CYP2D6 Allelic Variants (CYP2D6.2, 10, 14A-B, 18, 27, 36, 39, 47-51, 53-55, and 57)
Drug Metab. Dispos., December 1, 2008; 36(12): 2460 - 2467.
[Abstract] [Full Text] [PDF]


Home page
Am. J. PsychiatryHome page
N. L. Henry, V. Stearns, D. A. Flockhart, D. F. Hayes, and M. Riba
Drug Interactions and Pharmacogenomics in the Treatment of Breast Cancer and Depression
Am J Psychiatry, October 1, 2008; 165(10): 1251 - 1255.
[Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
M. P. Goetz, V. J. Suman, F. J. Couch, M. M. Ames, J. M. Rae, M. G. Erlander, X.-J. Ma, D. C. Sgroi, C. A. Reynolds, W. L. Lingle, et al.
Cytochrome P450 2D6 and Homeobox 13/Interleukin-17B Receptor: Combining Inherited and Tumor Gene Markers for Prediction of Tamoxifen Resistance
Clin. Cancer Res., September 15, 2008; 14(18): 5864 - 5868.
[Abstract] [Full Text] [PDF]


Home page
BMJHome page
N. C Turner and A. L Jones
Management of breast cancer--Part II
BMJ, July 11, 2008; 337(jul11_2): a540 - a540.
[Full Text]


Home page
JNCI J Natl Cancer InstHome page
D. F. Hayes, V. Stearns, J. Rae, D. Flockhart, and on behalf of the Consortium on Breast Cancer Pharm
A Model Citizen? Is Tamoxifen More Effective Than Aromatase Inhibitors if We Pick the Right Patients?
J Natl Cancer Inst, May 7, 2008; 100(9): 610 - 613.
[Full Text] [PDF]


Home page
JCOHome page
Z. Desta and D. A. Flockhart
In Reply
J. Clin. Oncol., April 1, 2008; 26(10): 1765 - 1766.
[Full Text] [PDF]


Home page
JCOHome page
N. U. Lin and E. P. Winer
Advances in Adjuvant Endocrine Therapy for Postmenopausal Women
J. Clin. Oncol., February 10, 2008; 26(5): 798 - 805.
[Abstract] [Full Text] [PDF]


Home page
JCOHome page
F. Eisinger
CYP2D6 and Ockham's Razor
J. Clin. Oncol., February 1, 2008; 26(4): 686 - 687.
[Full Text] [PDF]


Home page
JCOHome page
Z. Desta and D. A. Flockhart
Germline Pharmacogenetics of Tamoxifen Response: Have We Learned Enough?
J. Clin. Oncol., November 20, 2007; 25(33): 5147 - 5149.
[Full Text] [PDF]



About
JCO
 Editorial
Roster
 Advertising
Information
 Librarians &
Institutions
 Rights &
Permissions
 PDA Services

Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
Terms and Conditions of Use
  HighWire Press HighWire Press™ assists in the publication of JCO Online