Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/209297
Title: Significant Effect of Polymorphisms in CYP2D6 on Response to Tamoxifen Therapy for Breast Cancer: A Prospective Multicenter Study
Authors: Zembutsu, Hitoshi
Nakamura, Seigo
Akashi-Tanaka, Sadako
Kuwayama, Takashi
Watanabe, Chie
Takamaru, Tomoko
Takei, Hiroyuki
Ishikawa, Takashi
Miyahara, Kana
Matsumoto, Hiroshi
Hasegawa, Yoshie
Kutomi, Goro
Shima, Hiroaki
Satomi, Fukino
Okazaki, Minoru
Zaha, Hisamitsu
Onomura, Mai
Matsukata, Ayami
Sagara, Yasuaki
Baba, Shinichi
Yamada, Akimitsu
Shimada, Kazuhiro
Shimizu, Daisuke
Tsugawa, Koichiro
Shimo, Arata
Tan, Ern Yu
Hartman, Mikael 
Chan, Ching-Wan 
Lee, Soo Chin 
Nakamura, Yusuke
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
PATIENTS RECEIVING TAMOXIFEN
KI-67 LABELING INDEX
ADJUVANT TAMOXIFEN
GENETIC POLYMORPHISMS
POSTMENOPAUSAL WOMEN
CLINICAL-OUTCOMES
ESTROGEN-RECEPTOR
ACTIVE METABOLITE
GENOTYPE
ASSOCIATION
Issue Date: 15-Apr-2017
Publisher: AMER ASSOC CANCER RESEARCH
Citation: Zembutsu, Hitoshi, Nakamura, Seigo, Akashi-Tanaka, Sadako, Kuwayama, Takashi, Watanabe, Chie, Takamaru, Tomoko, Takei, Hiroyuki, Ishikawa, Takashi, Miyahara, Kana, Matsumoto, Hiroshi, Hasegawa, Yoshie, Kutomi, Goro, Shima, Hiroaki, Satomi, Fukino, Okazaki, Minoru, Zaha, Hisamitsu, Onomura, Mai, Matsukata, Ayami, Sagara, Yasuaki, Baba, Shinichi, Yamada, Akimitsu, Shimada, Kazuhiro, Shimizu, Daisuke, Tsugawa, Koichiro, Shimo, Arata, Tan, Ern Yu, Hartman, Mikael, Chan, Ching-Wan, Lee, Soo Chin, Nakamura, Yusuke (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.
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.
Source Title: CLINICAL CANCER RESEARCH
URI: https://scholarbank.nus.edu.sg/handle/10635/209297
ISSN: 10780432
15573265
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