Significant Effect of Polymorphisms in CYP2D6 on Response to Tamoxifen Therapy for Breast Cancer: A Prospective Multicenter Study.

Autor:	Zembutsu H; Division of Genetics, National Cancer Center Research Institute, Tokyo, Japan. hzenbuts@ncc.go.jp., Nakamura S; Department of Breast Surgery, Showa University, Tokyo, Japan., Akashi-Tanaka S; Department of Breast Surgery, Showa University, Tokyo, Japan., Kuwayama T; Department of Breast Surgery, Showa University, Tokyo, Japan., Watanabe C; Department of Breast Surgery, Showa University, Tokyo, Japan., Takamaru T; Department of Breast Surgery, Showa University, Tokyo, Japan., Takei H; Department of Breast Surgery, Nippon Medical School, Tokyo, Japan., Ishikawa T; Department of Breast Surgery, Tokyo Medical University, Tokyo, Japan., Miyahara K; Department of Breast Surgery, Tokyo Medical University, Tokyo, Japan., Matsumoto H; Department of Breast Surgery, Saitama Cancer Center, Saitama, Japan., Hasegawa Y; Department of Breast Surgery, Hirosaki Municipal Hospital, Hirosaki, Japan., Kutomi G; 1st Department of Surgery, Sapporo Medical University, Sapporo, Japan., Shima H; 1st Department of Surgery, Sapporo Medical University, Sapporo, Japan., Satomi F; 1st Department of Surgery, Sapporo Medical University, Sapporo, Japan., Okazaki M; Department of Breast Surgery, Sapporo Breast Surgical Clinic, Sapporo, Japan., Zaha H; Department of Breast Surgery, Nakagami Hospital, Okinawa, Japan., Onomura M; Department of Breast Surgery, Nakagami Hospital, Okinawa, Japan., Matsukata A; Department of Breast Surgery, Sagara Hospital, Kagoshima, Japan., Sagara Y; Department of Breast Surgery, Sagara Hospital, Kagoshima, Japan., Baba S; Department of Breast Surgery, Sagara Hospital, Kagoshima, Japan., Yamada A; Department of Breast and Thyroid Surgery, Yokohama City University Medical Center, Yokohama, Japan., Shimada K; Department of Breast and Thyroid Surgery, Yokohama City University Medical Center, Yokohama, Japan., Shimizu D; Department of Breast Surgery, Yokohama Minato Red Cross Hospital, Yokohama, Japan., Tsugawa K; Department of Breast and Endocrine Surgery, St. Marianna University School of Medicine Hospital, Kawasaki, Japan., Shimo A; Department of Breast and Endocrine Surgery, St. Marianna University School of Medicine Hospital, Kawasaki, Japan., Tan EY; Department of General Surgery, Tan Tock Seng Hospital, Singapore., Hartman M; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore., Chan CW; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore., Lee SC; Department of Hematology Oncology, National University Cancer Institute, National University Health System, Singapore., Nakamura Y; Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, Illinois.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2017 Apr 15; Vol. 23 (8), pp. 2019-2026. Date of Electronic Publication: 2016 Oct 19.
DOI:	10.1158/1078-0432.CCR-16-1779
Abstrakt:	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. We prospectively 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. Clin Cancer Res; 23(8); 2019-26. ©2016 AACR . (©2016 American Association for Cancer Research.)
Databáze:	MEDLINE
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