Abstract PD05-08: Lack of Significant Association between CYP2D6 Polymorphisms and Clinical Outcomes of Adjuvnt Tamoxifen Therapy

Purpose: CYP2D6 variant alleles have been suspected to influence on the clinical efficacy of tamoxifen because CYP2D6 is an enzyme which metabolizes tamoxifen into its active forms, endoxifen and 4-hydroxytomoxifen. This study was performed to investigate the correlation between the polymorphisms in CYP2D6 and the clinical outcome of patients receiving tamoxifen. Methods: Between April 2001 and February 2010, 481 patients with hormone receptor-positive, invasive breast cancer receiving tamoxifen monotherapy in Seoul National University Hospital were studied. we analyzed the patients’ CYP2D6 alleles with the technique of PCR and SNaPshot using the blood samples cultured just before the every surgery and investigated the relationships of allelic variants of CYP2D6 to the disease-free survival by the Kaplan-Meier method and Log rank test Results: Each part of all patients’ alleles was genotyped into CYP2D6*1, CYP2D6*2, CYP2D6*5, CYP2D6*10, CYP2D6*41 and All the patients were categorized into 3 types, i.e. 51 homogenous wild type patients, 217 heterogenous variant type ones and 213 homogenous variant type ones according to their allelic types. There was no difference in age, pT, pN, follow up period among these patients. The rate of events which is defined as locoreginal metastasis, distant metastasis, contralateral breast cancer was 7.1%(34 patients totally). Only 2 patients were died due to pulmonary complication with distant metastasis. The number of variant alleles were not associated with the disease free survival.(P = .162; 95% CI in patients with one variant allele vs patients without variant allele and P = .215; 95% CI in patients with two variant alleles vs patients without variant allele) And the number of non-functional alleles were not associated with the disease free survival either.(P = .171; 95% CI in patients with one non-functional allele(CYP2D6*5, CYP2D6*10, CYP2D6*41 ) vs patients with two functional alleles(CYP2D6*1, CYP2D6*2) and P = .187; 95% CI in patients with two non-functional alleles vs patients with two functional alleles) Even in the subgroups of stage I, stage II or more, premenopause, and postmenopause, there was no difference found in disease free survival. Conclusion: Out results suggest the clinical outcome of the patients who are receiving tamoxifen therapy is independent of the patients’ polymorphisms in CYP2D6 and need more sophisticated investigation into the relationship of the process metabolizing tomoxifen to the clinical effect in the patient9s body. Key Words: tomoxifen, CYP2D6, polymorphism Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD05-08.