CYP2D6 Genotype and Tamoxifen Response in Postmenopausal Women with Endocrine-Responsive Breast Cancer: The Breast International Group 1-98 Trial

Regan, Meredith M.; Leyland‐Jones, Brian; Bouzyk, Mark; Pagani, Olivia; Tang, Weining; Kammler, Roswitha; Dell’Orto, Patrizia; Biasi, Maria Olivia; Thürlimann, Beat; Lyng, Maria Bibi; Ditzel, Henrik J.; Neven, Patrick; Debled, Marc; Maibach, Rudolf; Price, Karen N.; Gelber, Richard D.; Coates, Alan S.; Goldhirsch, Aron; Rae, James M.; Viale, Giuseppe

doi:10.1093/jnci/djs125

Cited by 312 publications

(250 citation statements)

References 35 publications

Supporting

Mentioning

225

Contrasting

Unclassified

Order By: Relevance

“…Goetz et al [27] , have proven a statistically important incidence of negative events within carriers of poor CYP2D6 variants, while the two other studies failed to confirm such an association. Although they favour against a CYP2D6 genetic testing prior to tamoxifen therapy, it should be mentioned that both studies showed a substantial departure from the Hardy-Weinberg equilibrium regarding the frequency of allele*4 [25,26] .…”

Section: Discussionmentioning

confidence: 90%

“…It is important to mention that the three latest large studies refer exclusively to postmenopausal women with ER positive breast cancer disease [25][26][27] . Goetz et al [27] , have proven a statistically important incidence of negative events within carriers of poor CYP2D6 variants, while the two other studies failed to confirm such an association.…”

Section: Discussionmentioning

confidence: 99%

“…The Breast International Group (BIG) 1-98 study was a randomized, phase 3, double-blind trial that compared five years of treatment with various adjuvant endocrine therapy regimens in postmenopausal women with ER+ breast cancer. Regan et al [26] investigated the clinical relevance of CYP2D6 phenotype by obtaining tissue samples from 4861 of 8010 postmenopausal women who enrolled in this prospective trial. A specific correlation for allele *4 has been also performed.…”

Section: Researchmentioning

confidence: 99%

“…August 10, 2014|Volume 5|Issue 3| WJCO|www.wjgnet.com Goetz et al [8] RFS DFS OS NS (P = 0.075) NS (P = 0.097) NS Worse (P = 0.005) Worse (P = 0.008) NS Scroth et al [9,10] RR MR [12] DFS 118 mo 114 mo 98 mo Bijl et al [13] RBCM NS Increased (P = 0.041) Newman et al [16] OS Worse Karle et al [17] PFS 14 mo 9 mo Abraham et al [20] BCSS NS Nowell [23] BCR, OS NS NS Rae et al [25] RR NS NS Regan et al [26] BCE prospective multicenter randomised trial (Austrian Breast and Colorectal Study 8 -ABCSG trial 8) have been newly published. In this cohort 3901 postmenopausal patients with resected ER+ early cancer were randomised to receive either five years tamoxifen or two years tamoxifen followed by anastrazole administration over three more years.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Impact of CYP2D*6 in the adjuvant treatment of breast cancer patients with tamoxifen

Markopoulos

Kykalos

Mantas

2014

WJCO

View full text Add to dashboard Cite

Biotransformation of tamoxifen to the potent antiestrogen endoxifen is performed by cytochrome P450 (CYP) enzymes, in particular the CYP2D6 isoform. CYP2D6*4 is one of the most frequent alleles associated with loss of enzymatic activity. The incidence of CYP2D6*4 among Caucasians is estimated up to 27%, while it is present in up to 90% of all poor metabolizers within the Caucasian population. The hypothesis under question is whether the presence of one or two non-functioning (null) alleles predicts an inferior outcome in postmenopausal women with breast cancer receiving adjuvant treatment with tamoxifen. The numerous existing studies investigating the association of CYP2D6 with treatment failure in breast cancer are inconsistent and give rather conflicting results. Currently, routine CYP2D6 testing among women with breast cancer is not recommended and the significance of CYP2D6 phenotype in decision making regarding the administration of tamoxifen is unclear. The present study summarizes current literature regarding clinical studies on CYP2D6*4, particularly in terms of response to tamoxifen therapy and breast cancer outcome.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: CYP2D6; Tamoxifen; Breast cancer; Adjuvant treatment Core tip: Currently, routine cytochrome P450 (CYP)2D6 testing among women with breast cancer is not recommended and the significance of CYP2D6 phenotype in decision making regarding the administration of tamoxifen is unclear. The present study summarizes current literature regarding clinical studies on CYP2D6*4, particularly in terms of response to tamoxifen therapy and breast cancer outcome.Markopoulos C, Kykalos S, Mantas D. Impact of CYP2D*6 in the adjuvant treatment of breast cancer patients with tamoxifen.

show abstract

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Researchmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Impact of CYP2D*6 in the adjuvant treatment of breast cancer patients with tamoxifen

Markopoulos

Kykalos

Mantas

2014

WJCO

View full text Add to dashboard Cite

show abstract

“…Hence, tamoxifen remains the gold standard for ER (+) breast cancer. However, tamoxifen efficacy varies widely, many breast cancer patients with adjuvant tamoxifen remain free of recurrence but 30-50% suffer relapse [7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Does CYP2D6 Genotyping have a Role in Guiding Tamoxifen Therapy?

Mokbel¹,

Mokbel²

2017

Biochem Mol biol J

View full text Add to dashboard Cite

Inter-individual variability to drug response is a major concern in the field of oncology. In the era of "targeted" therapy, optimal treatment outcomes can be achieved by more individualized initial dosing and/or alternative treatment according to the patient's genetic make-up. Although several genes are responsible for the interindividual variability in drug metabolism and response, the Cytochrome P450 enzymes are the most widely validated and clinically utilized. Pharmacogenetic testing of CYP2D6 alleles was the first FDA approved test due to its involvement in the metabolism of a wide range of drugs such as the anti-cancer drug tamoxifen (Nolvadex ® ), to which clinical response varies widely among patients.Identifying determinants and predictors of the variable response or non-response to tamoxifen can facilitate therapeutic dose measurement or even determine the choice of alternative agents (e.g. aromatase inhibitors). Several clinical trials have shown that genetic variants associated with slower metabolism of tamoxifen may lead to lower than expected blood levels of its pharmacologically active metabolites and thus shorter recurrence-free survival. CYP2D6 genotyping can be clinically useful for selecting adjuvant therapy, improving the clinical outcome of tamoxifen and potentially reducing overall costs of treatment. However, CYP2D6 phenotypebased recommendations for tamoxifen have not been developed and guidelines linking the CYP2D6 status to personalized oncologic care do not exist and therefore clinicians' uptake of the testing has remained very low. Large prospective randomized clinical trials are required to assess whether CYP2D6 genotype can robustly predict treatment outcome of tamoxifen and improve overall survival.

show abstract

Cancer Pharmacogenomics

Hertz

McLeod

2015

Reviews in Cell Biology and Molecular Medicine

View full text Add to dashboard Cite

CYP2D6 Genotype and Tamoxifen Response in Postmenopausal Women with Endocrine-Responsive Breast Cancer: The Breast International Group 1-98 Trial

Cited by 312 publications

References 35 publications

Impact of CYP2D*6 in the adjuvant treatment of breast cancer patients with tamoxifen

Impact of CYP2D*6 in the adjuvant treatment of breast cancer patients with tamoxifen

Does CYP2D6 Genotyping have a Role in Guiding Tamoxifen Therapy?

Cancer Pharmacogenomics

Contact Info

Product

Resources

About