title: Lack of any association between functionally significant CYP2D6 polymorphisms and clinical outcomes in early breast cancer patients receiving adjuvant tamoxifen treatment.
abstract: Active metabolites of tamoxifen are formed mainly by the action of cytochrome P450 2D6 (CYP2D6). Since there are controversies regarding associations between CYP2D6 polymorphisms and outcomes among women with early breast cancer (EBC) treated with tamoxifen, the present evaluation of links with clinical outcomes was conducted. We analyzed a total of 716 patients treated with tamoxifen for hormone receptor positive EBC between 2001 and 2005 at the National Cancer Center, Korea. All patients received tamoxifen 20 mg/day for more than 6 months. DNA obtained from whole blood samples was genotyped for CYP2D6 variants associated with reduced (*10, *41) and absent (*5) activity. Of the total of 716 patients, 558 (77.9%) received adjuvant or neoadjuvant chemotherapy prior to the tamoxifen therapy. From the genotyping of CYP2D6, 152 (21.2%) patients were classified as having the wild type (W/W), 376 (52.7%) one variant allele (W/V), and 188 (26.1%) two variant alleles (V/V). Seventy (9.8%) patients experienced disease recurrence with a median follow-up of 5.6 (range, 0.6-10.3) years. Although known prognostic factors, including tumor size, nodal status, Ki67, PgR negativity, and HER2 positivity showed strong associations with the recurrence free survival (RFS) in this population, no significant association with any of the CYP2D6 genetic variants was evident (P = 0.61; hazard ratio [HR] = 1.14; 95% CI 0.68-1.92). This remained the case after subgroup analysis according to different adjuvant treatments. Polymorphisms of CYP2D6 were not associated with clinical outcomes in EBC patients receiving adjuvant tamoxifen treatment.
authors: Center for Breast Cancer, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-769, Korea. parkih@ncc.re.kr
authors: In Hae
authors: IH
authors: Park
authors: Jungsil
authors: J
authors: Ro
authors: Sohee
authors: S
authors: Park
authors: Hyeong-Seok
authors: HS
authors: Lim
authors: Keun Seok
authors: KS
authors: Lee
authors: Han Sung
authors: HS
authors: Kang
authors: So-Youn
authors: SY
authors: Jung
authors: Seeyeon
authors: S
authors: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence; D012307:Risk Factors; D016019:Survival Analysis; D013629:Tamoxifen / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D019389:Cytochrome P-450 CYP2D6