Please use this identifier to cite or link to this item: https://doi.org/10.1158/1078-0432.CCR-16-1779
Title: Significant effect of polymorphisms in CYP2D6 on response to tamoxifen therapy for breast cancer: A prospective multicenter study
Authors: Zembutsu H.
Nakamura S.
Akashi-Tanaka S.
Kuwayama T.
Watanabe C.
Takamaru T.
Takei H.
Ishikawa T.
Miyahara K.
Matsumoto H.
Hasegawa Y.
Kutomi G.
Shima H.
Satomi F.
Okazaki M.
Zaha H.
Onomura M.
Matsukata A.
Sagara Y.
Baba S.
Yamada A.
Shimada K.
Shimizu D.
Tsugawa K.
Shimo A.
Tan E.Y.
Hartman M. 
Chan C.-W. 
Lee S.C.
Nakamura Y.
Issue Date: 15-Apr-2017
Publisher: American Association for Cancer Research Inc.
Citation: Zembutsu H., Nakamura S., Akashi-Tanaka S., Kuwayama T., Watanabe C., Takamaru T., Takei H., Ishikawa T., Miyahara K., Matsumoto H., Hasegawa Y., Kutomi G., Shima H., Satomi F., Okazaki M., Zaha H., Onomura M., Matsukata A., Sagara Y., Baba S., Yamada A., Shimada K., Shimizu D., Tsugawa K., Shimo A., Tan E.Y., Hartman M., Chan C.-W., Lee S.C., Nakamura Y. (2017-04-15). Significant effect of polymorphisms in CYP2D6 on response to tamoxifen therapy for breast cancer: A prospective multicenter study. Clinical Cancer Research 23 (8) : 2019-2026. ScholarBank@NUS Repository. https://doi.org/10.1158/1078-0432.CCR-16-1779
Abstract: Purpose: CYP2D6 is the key enzyme responsible for the generation of the potent active metabolite of tamoxifen, "endoxifen." There are still controversial reports questioning the association between CYP2D6 genotype and tamoxifen efficacy. Hence, we performed a prospective multicenter study to evaluate the clinical effect of CYP2D6 genotype on tamoxifen therapy. Experimental Design: We enrolled 279 patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative, invasive breast cancer receiving preoperative tamoxifen monotherapy for 14 to 28 days. Ki-67 response in breast cancer tissues after tamoxifen therapy was used as a surrogate marker for response to tamoxifen.Weprospectively investigated the effects of allelic variants of CYP2D6 on Ki-67 response, pathological response, and hot flushes. Results: Ki-67 labeling index in breast cancer tissues significantly decreased after preoperative tamoxifen monotherapy (P = 0.0000000000000013). Moreover, proportion and Allred scores of estrogen receptor-positive cells in breast cancer tissues were significantly associated with Ki-67 response (P = 0.0076 and 0.0023, respectively). Although CYP2D6 variants were not associated with pathologic response nor hot flushes, they showed significant association with Ki-67 response after preoperative tamoxifen therapy (P = 0.018; between two groups, one with at least one wild-type allele and the other without a wild-type allele). Conclusions: This is the first prospective study evaluating the relationship between CYP2D6 variants and Ki-67 response after tamoxifen therapy. Our results suggest that genetic variation in CYP2D6 is a key predictor for the response to tamoxifen in patients with breast cancer. � 2016 American Association for Cancer Research.
Source Title: Clinical Cancer Research
URI: http://scholarbank.nus.edu.sg/handle/10635/146689
ISSN: 10780432
DOI: 10.1158/1078-0432.CCR-16-1779
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

8
checked on Sep 17, 2018

Page view(s)

2
checked on Sep 13, 2018

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.