RECOMMENDATIONS In addition to estrogen and progesterone receptors and human epidermal growth factor receptor 2 , the panel found sufficient evidence of clinical utility for the biomarker assays Oncotype DX , EndoPredict , PAM50 , Breast Cancer Index , and urokinase plasminogen activator and plasminogen activator inhibitor type 1 in specific subgroups of breast cancer .
No biomarker except for estrogen receptor , progesterone receptor , and human epidermal growth factor receptor 2 was found to guide choices of specific treatment regimens .
PURPOSE To provide recommendations on appropriate use of breast tumor biomarker assay results to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer .
CYP2D6 and UGT2B7 genotype and risk of recurrence in tamoxifen-treated breast cancer patients.
BACKGROUND Adjuvant tamoxifen therapy substantially decreases the risk of recurrence and mortality in women with hormone ( estrogen and /or progesterone ) receptor-positive breast cancer . Previous studies have suggested that metabolic conversion of tamoxifen to endoxifen by cytochrome P450 2D6 ( CYP2D6 ) is required for patient benefit from tamoxifen therapy . METHODS Tumor specimens from a subset of postmenopausal patients with hormone receptor-positive early-stage ( stages I , II , and IIIA ) breast cancer , who were enrolled in the r and omized double-blind Arimidex , Tamoxifen , Alone or in Combination ( ATAC ) clinical trial , were genotyped for variants in CYP2D6 ( N = 1203 patients :  anastrozole [ trade name : Arimidex ] group , n = 615 patients ; tamoxifen group , n = 588 patients ) and UDP-glucuronosyltransferase-2B7 ( UGT2B7 ) , whose gene product inactivates endoxifen  ( N = 1209 patients ; anastrozole group , n = 606 patients ;  tamoxifen  group , n = 603 patients ) . Genotyping was performed using polymerase chain reaction-based TaqMan assays . Based on the genotypes for CYP2D6 , patients were classified as poor metabolizer ( PM ) , intermediate metabolizer ( IM ) , or extensive metabolizer ( EM ) phenotypes . We evaluated the association of CYP2D6 and UGT2B7 genotype with distant recurrence ( primary endpoint ) and any recurrence ( secondary endpoint ) by estimating the hazard ratios ( HRs ) and corresponding 95 % confidence intervals ( CIs ) using Cox proportional hazards models . All statistical tests were two-sided . RESULTS After a median follow-up of 10 years , no statistically significant associations were observed between CYP2D6 genotype and recurrence in tamoxifen-treated patients ( PM vs EM : HR for distant recurrence = 1.25 , 95 % CI = 0.55 to 3.15 , P = .64 ; HR for any recurrence = 0.99 , 95 % CI = 0.48 to 2.08 , P = .99 ) . A near-null association was observed between UGT2B7 genotype and recurrence in tamoxifen-treated patients . No associations were observed between CYP2D6 and UGT2B7 genotypes and recurrence in anastrozole-treated patients . CONCLUSION The results do not support the hypothesis that CYP2D6 genotype predicts clinical benefit of adjuvant tamoxifen treatment among postmenopausal breast cancer patients
RECOMMENDATIONS In addition to estrogen and progesterone receptors and human epidermal growth factor receptor 2 , the panel found sufficient evidence of clinical utility for the biomarker assays Oncotype DX , EndoPredict , PAM50 , Breast Cancer Index , and urokinase plasminogen activator and plasminogen activator inhibitor type 1 in specific subgroups of breast cancer .
No biomarker except for estrogen receptor , progesterone receptor , and human epidermal growth factor receptor 2 was found to guide choices of specific treatment regimens .
PURPOSE To provide recommendations on appropriate use of breast tumor biomarker assay results to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer .