Table 3.
Summary of main studies that evaluated genetic variants and tamoxifen-associated long-term outcomes
| Study | Study overview | Main results |
|---|---|---|
| Goetz et al., 2005 (Refs 27, 28) | 256 postmenopausal women with ER+/PR+ tumours; tamoxifen (20 mg/day) for 5 yearsa | CYP2D6*4/*4 vs other groups |
| Higher risk of recurrence: | ||
| RFS HR = 1.85, P = 0.176 | ||
| DFS HR = 1.86, P = 0.089 | ||
| Schroth et al., 2007 (Ref. 32) | 486 pre- and postmenopausal women; 206 adjuvant tamoxifen (100% ER+), 280 chemotherapy or nothing (54% ER+) | Tamoxifen-treated PMs vs other groups |
| Higher risk of recurrence: | ||
| RFS HR = 2.24, P = 0.02 | ||
| EFSR HR = 1.89, P = 0.02 | ||
| Wegman et al., 2005 (Ref. 29) | 226 postmenopausal women; 112 (70% ER+) tamoxifen (40 mg/day) for 2 years | CYP2D6*4 carrier |
| Lower risk of recurrence: RR = 0.28, P = 0.0089 | ||
| SULT1A1*1/*1 carrier | ||
| Lower risk of recurrence: RR = 0.48, P = 0.0074 | ||
| CYP2D6*4 and /or SULT1A1*1/*1 carrier | ||
| Lower risk of distant recurrence: RR = 0.38, P = 0.0041 | ||
| Wegman et al., 2007 (Ref. 30) | 677 peri-and postmenopausal ER+ women; 238 randomised to tamoxifen (40 mg/day or 20 mg/day) for 2 or 5 years, 439 tamoxifen (40 mg/day) for 2 or 5 years (before 1994) or 20 mg/day for 5 years (after 1994) | CYP2D6*4/*4 vs CYP2D6*1/*1 or CYP2D6*1: |
| Improved DFS: P = 0.05, and 0.04, respectively | ||
| CYP3A5*3/*3 | ||
| Improved RFS: HR = 0.20, P = 0.002 | ||
| Lim et al., 2007 (Ref. 33) | 211 pre- and postmenopausal women (12 with metastatic breast cancer; 190 adjuvant); tamoxifen (20 mg/day) | CYP2D6*10/*10 carriers vs other groups |
| Lower concentration of tamoxifen metabolites: P < 0.0001 | ||
| CYP2D6*10 | ||
| More often found among nonresponders: | ||
| 100% vs 50%; P = 0.0186; Median TTP = 5 vs 21.8 months; P = 0.0032 | ||
| Nowell et al., 2005 (Ref. 31) | 337 pre- and postmenopausal women (retrospective);160 tamoxifen, 177 no tamoxifen | CYP2D6*4 vs other |
| Lower risk of recurrence: | ||
| DFS HR = 0.67, P = NS | ||
| OS HR = 0.79, P = NS | ||
| Kiyotani et al., 2008 (Ref. 34) | 67 pre- and postmenopausal women (retrospective); tamoxifen (20 mg/day) for 5 years | CYP2D6*10/*10 vs *1v*1 |
| Higher risk of recurrence: | ||
| RFS HR = 10.94, P = 0.036 | ||
| Bonanni et al., 2006 (Ref. 35) | 46 women from a prospective chemoprevention study; tamoxifen (20 mg/day) for 5 years vs placebo for 5 years | Higher frequency of breast cancer in CYP2D6*4/*4 carrier: |
| 8.7% vs 0.7% in other |
a
Women who received 5 years of tamoxifen and 1 year of fluoxymesterone were not included in the pharmacogenetics study.
Abbreviations: DFS, disease-free survival; EFSR, event-free survival rate; EM, extensive metaboliser; ER, estrogen (estrogen) receptor; HR, hazard ratio, IM, intermediate metaboliser; NS, statistically not significant, OS, overall survival; PM, poor metaboliser; PR, progesterone receptor; RFS, relapse-free survival; RR, relative risk; TTP, time to progression; UM, ultrarapid metaboliser; vs, versus.