Toremifene, rather than tamoxifen, might be a better option for the adjuvant endocrine therapy in CYP2D6*10T/T genotype breast cancer patients in China

被引:20
作者
Lan, Bo [1 ,2 ]
Ma, Fei [1 ,2 ]
Chen, Shanshan [1 ,2 ]
Wang, Wenna [1 ,2 ]
Li, Qiao [1 ,2 ]
Fan, Ying [1 ,2 ]
Luo, Yang [1 ,2 ]
Cai, Ruigang [1 ,2 ]
Wang, Jiayu [1 ,2 ]
Yuan, Peng [1 ,2 ]
Zhang, Pin [1 ,2 ]
Li, Qing [1 ,2 ]
Xu, Binghe [1 ,2 ]
机构
[1] Chinese Acad Med Sci, Canc Hosp, Natl Clin Res Ctr Canc, Dept Med Oncol,Natl Canc Ctr, Beijing 100021, Peoples R China
[2] Peking Union Med Coll, Beijing 100021, Peoples R China
关键词
breast cancer; TAM; TOR; CYP2D6; SNP; CYP2D6; POLYMORPHISMS; OUTCOMES; ASSOCIATION; STATISTICS; METABOLISM; SURVIVAL; EFFICACY; ASIANS; ALLELE; WOMEN;
D O I
10.1002/ijc.31639
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Toremifene (TOR) is a valid and safe alternative to tamoxifen (TAM) for adjuvant endocrine therapy in breast cancer patients with a metabolic pathway that differs from that of TAM. TOR might have a therapeutic advantage in certain subgroups of patients, such as Chinese women with the CYP2D6 *10 (c.100C > T) T/T genotype, who would get less benefit when receiving adjuvant TAM treatment. A total of 230 breast cancer patients who received adjuvant TAM (n = 115) or TOR (n = 115) at the National Cancer Center were analyzed. The CYP2D6 *10 genotype was not significantly associated with DFS in patients who received TOR (p = 0.737). Patients treated with TOR had a higher 5-year disease-free survival (DFS) rate than those treated with TAM (89.6% vs. 80.9%, p = 0.009). TOR treatment remained an independent prognostic marker of DFS in multivariate analysis compared with TAM (hazard ratio = 0.51; p = 0.014). For all of the 50 CYP2D6 *10 T/T genotype patients, TOR treatment group had a significantly higher 5-year DFS rate than TAM group (90.9% vs. 67.9%, p = 0.031). For the remaining 170 CYP2D6 *10 C/C or C/T genotype patients, there was no significant difference between the 5-year DFS rates of the TOR and TAM groups (89.2% vs. 85.1%, p = 0.188). The advantage of adjuvant TOR over TAM in Chinese breast cancer patients might be caused by the significant benefit obtained by the CYP2D6 *10 T/T patients, who accounted for one-fifth of the overall population. TOR might be a good option for adjuvant endocrine therapy in this subgroup of patients in China.
引用
收藏
页码:2499 / 2504
页数:6
相关论文
共 31 条
[1]   CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants [J].
Bradford, LD .
PHARMACOGENOMICS, 2002, 3 (02) :229-243
[2]   Prediction of tamoxifen outcome by genetic variation of CYP2D6 in post-menopausal women with early breast cancer [J].
Brauch, Hiltrud ;
Schwab, Matthias .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2014, 77 (04) :695-703
[3]   Cancer Statistics in China, 2015 [J].
Chen, Wanqing ;
Zheng, Rongshou ;
Baade, Peter D. ;
Zhang, Siwei ;
Zeng, Hongmei ;
Bray, Freddie ;
Jemal, Ahmedin ;
Yu, Xue Qin ;
He, Jie .
CA-A CANCER JOURNAL FOR CLINICIANS, 2016, 66 (02) :115-132
[4]   Clinical Pharmacogenetics Implementation Consortium Guidelines for Cytochrome P450 2D6 Genotype and Codeine Therapy: 2014 Update [J].
Crews, K. R. ;
Gaedigk, A. ;
Dunnenberger, H. M. ;
Leeder, J. S. ;
Klein, T. E. ;
Caudle, K. E. ;
Haidar, C. E. ;
Shen, D. D. ;
Callaghan, J. T. ;
Sadhasivam, S. ;
Prows, C. A. ;
Kharasch, E. D. ;
Skaar, T. C. .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 2014, 95 (04) :376-382
[5]   Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials [J].
Davies, C. ;
Godwin, J. ;
Gray, R. ;
Clarke, M. ;
Darby, S. ;
McGale, P. ;
Wang, Y. C. ;
Peto, R. ;
Pan, H. C. ;
Cutter, D. ;
Taylor, C. ;
Ingle, J. .
LANCET, 2011, 378 (9793) :771-784
[6]   Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: Prominent roles for CYP3A and CYP2D6 [J].
Desta, Z ;
Ward, BA ;
Soukhova, NV ;
Flockhart, DA .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2004, 310 (03) :1062-1075
[7]   Adjuvant Ovarian Suppression in Premenopausal Breast Cancer [J].
Francis, Prudence A. ;
Regan, Meredith M. ;
Fleming, Gini F. ;
Lang, Istvan ;
Ciruelos, Eva ;
Bellet, Meritxell ;
Bonnefoi, Herve R. ;
Climent, Miguel A. ;
Da Prada, Gian Antonio ;
Burstein, Harold J. ;
Martino, Silvana ;
Davidson, Nancy E. ;
Geyer, Charles E., Jr. ;
Walley, Barbara A. ;
Coleman, Robert ;
Kerbrat, Pierre ;
Buchholz, Stefan ;
Ingle, James N. ;
Winer, Eric P. ;
Rabaglio-Poretti, Manuela ;
Maibach, Rudolf ;
Ruepp, Barbara ;
Giobbie-Hurder, Anita ;
Price, Karen N. ;
Colleoni, Marco ;
Viale, Giuseppe ;
Coates, Alan S. ;
Goldhirsch, Aron ;
Gelber, Richard D. .
NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (05) :436-446
[8]   Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and Tamoxifen Therapy [J].
Goetz, Matthew P. ;
Sangkuhl, Katrin ;
Guchelaar, Henk-Jan ;
Schwab, Matthias ;
Province, Michael ;
Whirl-Carrillo, Michelle ;
Symmans, W. Fraser ;
McLeod, Howard L. ;
Ratain, Mark J. ;
Zembutsu, Hitoshi ;
Gaedigk, Andrea ;
van Schaik, Ron H. ;
Ingle, James N. ;
Caudle, Kelly E. ;
Klein, Teri E. .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 2018, 103 (05) :770-777
[9]   CYP2D6 Metabolism and Patient Outcome in the Austrian Breast and Colorectal Cancer Study Group Trial (ABCSG) 8 [J].
Goetz, Matthew P. ;
Suman, Vera J. ;
Hoskin, Tanya L. ;
Gnant, Michael ;
Filipits, Martin ;
Safgren, Stephanie L. ;
Kuffel, Mary ;
Jakesz, Raimund ;
Rudas, Margaretha ;
Greil, Richard ;
Dietze, Otto ;
Lang, Alois ;
Offner, Felix ;
Reynolds, Carol A. ;
Weinshilboum, Richard M. ;
Ames, Matthew M. ;
Ingle, James N. .
CLINICAL CANCER RESEARCH, 2013, 19 (02) :500-507
[10]   A comparison of survival outcomes and side effects of toremifene or tamoxifen therapy in premenopausal estrogen and progesterone receptor positive breast cancer patients: a retrospective cohort study [J].
Gu, Ran ;
Jia, Weijuan ;
Zeng, Yunjie ;
Rao, Nanyan ;
Hu, Yue ;
Li, Shunrong ;
Wu, Jiannan ;
Jin, Liang ;
Chen, Lijuan ;
Long, Meijun ;
Chen, Kai ;
Chen, Lili ;
Xiao, Qiaozhen ;
Wu, Mei ;
Song, Erwei ;
Su, Fengxi .
BMC CANCER, 2012, 12