The Impact of CYP2D6 Genotyping on Tamoxifen Treatment
Abstract
:1. Introduction
2. CYP2D6 Genotype and Tamoxifen Metabolism
CYP2D6 Alleles | Predicted Enzyme Activity |
---|---|
*1, *2, *33 and *35 | Normal |
*3,*4,*5,*6,*7,*8,*11-*16, *18, *19,*20,*21, *36, *38,*40, *42, *44, *56, *62, 4xn, 6xn and 36xn | None |
*9,*10, *17, *29, *41, *69, 29xn and 41xn | Reduced |
*22,*23-*28, *30-*32, *34,*37,*39, *43,*45-*68, *70-*75 | Unknown |
*1xn, *2xn,*35xn | Increased |
3. CYP2D6 Genotype and Tamoxifen Therapy
4. CYP2D6 Genotype in Non-Caucasian Tamoxifen Treated Breast Cancer Patients
5. Tamoxifen Side Effects and CYP2D6
Author | Patients | Origin of study | CYP2D6 alleles typed | Median Follow up (years) | CYP2D6 inhibitors in PM definition | Comparison | Main Results |
---|---|---|---|---|---|---|---|
Goetz et al. 2005 [21] | N=190 ER+ve Postmenopausal TAM only | American | *4, *6 | 11.4 | No | PM vs. EM + hetEM | DFS HR, 1.86; P = 0.089 RFS HR, 1.85; P= 0.176 OS HR, 1.12; P= 0.780 |
Goetz et al. 2007 [43] | Same as [21] | American | *4, *6 | 11.4 | Yes | PM vs. EM + IM + hetEM | RFS HR, 1.74; P = 0.017 TTBR HR, 1.91; P=0.034 DFS HR, 1.60; P= 0.027 OS HR, 1.34; P= 0.223 |
Goetz et al. 2008* [22] | Same as [21] | American | *3, *4, *6, *10, *17, *41 | 14.5 | Yes | PM vs. EM | TTR HR 4.0, P=0.001 DFS HR 2.0, P=0.02 |
Schroth et al. 2007 [23] | N=206 ER+ve TAM only | German | *4, *5, *10, *41 | 5.9 | No | hetEM + IM+PM vs. EM | RFT HR 2.24; P = 0.02 EFS HR 1.89; P = 0.02 |
Newman et al. 2008 [24] | N=115 Familial breast cancer ER+ and -ve Adj TAM Some received CT | British | *3,*4,*5, *41 | 10 | Yes | PM vs. EM+ hetEM | TTR HR, 2.1; P = 0.14 OS HR, 2.5; P = 0.17 BRCA2 patients: TTR HR, 3.8; P = 0.083 OS HR, 9.7; P = 0.008 |
Bijl et al. 2009 [25] | N=85Adj TAM | Dutch | *4 | Not available | Yes | PM vs. EM | BCM HR, 4.0; P = 0.025 |
Gonzalez-Santiago et al. 2007 * [26] | N=84 Adj TAM | Spanish | *4 | 5.5 | No | hetEM + PM vs. EM | RFS HR, 2.82; P = 0.05 |
Ramon et al. 2009 [27] | N=91 ER+ve Adj TAM Some received CT | Spanish | Amplichip 33 alleles | 9 | No | *4/*4,*4/*4, *1/*5 and*2/*5 vs. the remaining genotypes | DFS HR not available, P = 0.016 |
Nowell et al. 2005 [28] | N=162 Adj TAM Some received CT | American | *3,*4,*6 | Not available | No | PM + hetEM vs. EM | OS HR, 0.77; P = 0.51 PFS HR, 0.67; P= 0.19 |
Wegman et al. 2005 [29] | N=112 ER + and -ve Some received CT Some received TAM | Sweden | *4 | 10.7 | No | Not applicable | Carriers of the CYP2D6*4 allele demonstrated a decreased risk of recurrence when treated with TAM(relative risk, 0.28; P =0.0089) |
Wegman et al. 2007 [30] | N=677 ER+ve Postmenopausal Some received CT, different dose-different duration of TAM | Sweden | *4 | 7.3 | No | PM vs.. EM + hetEM | RFS HR, <1; P = 0.055 |
Schroth et al. 2009 [31] | N=1325 TAM only | German / American | *3,*4,*5, *10,*41 | 6.3 | No | hetEM+IM +PM vs. EM PM vs. EM | EFS HR, 1.33; P=0.01 DFS HR, 1.29; P=0.02 TTR HR 1.90; p=0.02 |
Thompson et al. 2009* [32] | N=618 ER+ve Adj TAM Some received CT | British | Amplichip 33 alleles | 5.6 | No | hetEM+ IM +PM vs. EM | RFS HR 1.52, P=0.06 Postmenopausal, TAM only patients: RFS HR, 1.96; P=0.036 |
Kitoyani et al. 2008 [34] | N=67 TAM only ER+ve | Japanese | *4, *5, *6, *10, *14, *18, *21, *41 | 8 | No | IM vs. EM | RFS HR 10.04, P = 0.036 |
Xu et al. 2008 [35] | N=152 Adj TAM Some received CT No eligible women were taking CYP2D6 inhibitors | Chinese | *10 | 5.2 | - | IM vs. EM + hetEM | DFS HR 4.7, P=0.04 |
Okishiro et al 2009 [36] | N=173 ER+ve Adj TAM Some received CT and goserelin | Japanese | *10 | 4.6 | No | IM vs. EM+ hetEM | RFS HR 0.6, P= 0.39 |
Kitoyani et al. 2010 [37] | N=282 TAM only 67 patients reported previously [37] | Japanese | *4, *5, *6, *10, *14, *18, *21, *36, *41 | 7.1 | No | IM +PM vs. EM | RFS HR 9.52, P=.000036 |
6. CYP2D6 Inhibitors and Tamoxifen Therapy
7. Complexity of Tamoxifen Metabolism
8. Conclusions and Discussion
Acknowledgements
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Ferraldeschi, R.; Newman, W.G. The Impact of CYP2D6 Genotyping on Tamoxifen Treatment. Pharmaceuticals 2010, 3, 1122-1138. https://doi.org/10.3390/ph3041122
Ferraldeschi R, Newman WG. The Impact of CYP2D6 Genotyping on Tamoxifen Treatment. Pharmaceuticals. 2010; 3(4):1122-1138. https://doi.org/10.3390/ph3041122
Chicago/Turabian StyleFerraldeschi, Roberta, and William G. Newman. 2010. "The Impact of CYP2D6 Genotyping on Tamoxifen Treatment" Pharmaceuticals 3, no. 4: 1122-1138. https://doi.org/10.3390/ph3041122
APA StyleFerraldeschi, R., & Newman, W. G. (2010). The Impact of CYP2D6 Genotyping on Tamoxifen Treatment. Pharmaceuticals, 3(4), 1122-1138. https://doi.org/10.3390/ph3041122