Abstract 199P
Background
Tamoxifen plays a key role in the management of hormone receptor positive breast cancer patients. This pro-drug is converted into endoxifen by the cytochrome CYP2D6. CYP2D6's catalytic activity rate varies depending on its genetic polymorphisms. Several reports in the literature indicate that there are different CYP2D6 activity phenotypes that may influence tamofixen's efficacy. The aim of our work is to retrospectively analyse the effect of CYP2D6 genetic polymorphisms on clinical parameters such as disease free or overall survival rates in adjuvant tamoxifen-treated patients.
Methods
Serum samples from 219 female patients were collected and DNA was purified by using QIAcubeR kit (Qiagen). Then genetic polymorphisms were obtained upon matrix hibridation and massively sequenced by using AmpliChip CYP450R platform (Roche Molecular Systems, Inc.). The phenotypes were obtained using a prediction software. Correlation between metabolic rates and survival variables was further analysed through statistical tools such as Cox model and Kaplan-Meier method.
Results
The 219 patients were grouped as follows: 2.3% ultra-rapid, 78.5% efficient, 13.20% medium, and 6% poor metabolizers. Neither the different CYP2D6 metabolic phenotypes nor CYPD26 activity score, showed an impact over disease free and overall survival rates. The table below presents the effect of the phenotypes (UR ultra-rapid, EF efficient, IM intermediate, LE slow) and activity scores (AS) over overall survival using Kaplan-Meier estimation. Activity score: each allele is given a punctuation (0/0.5/1/2/3) and are finally grouped as follows: AS <1,5 or AS>=1,5. Table: 199P
| Variable | Median Survival (months) | IC (95%) | p-value |
| CYP2D6 phenotype (n = 213) | 0,727 | ||
| UR | 137,4 | 115,311 - 159,489 | |
| EF | 141,272 | 137,575 - 144,968 | |
| IM | 145,556 | 137,007 - 154,104 | |
| LE | 139,083 | 118,598 - 159,569 | |
| Activity Score (n=213) | 0,269 | ||
| AS<1,5 | 143,063 | 137,946 - 148,181 | |
| AS > = 1,5 | 140,417 | 135,874 - 144,959 |
Conclusions
Our study shows that CYP2D6 metabolic status has no impact in relapse variants (overall and disease free survival) in breast cancer patients treated with adjuvant tamoxifen, in agreement with previous reports on this subject.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.