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 genotype and tamoxifen response in postmenopausal women with endocrine-responsive breast cancer: the breast international group 1-98 trial.
BACKGROUND Adjuvant tamoxifen therapy is effective for postmenopausal women with endocrine-responsive breast cancer . Cytochrome P450 2D6 ( CYP2D6 ) enzyme metabolizes tamoxifen to clinical ly active metabolites , and CYP2D6 polymorphisms may adversely affect tamoxifen efficacy . In this study , we investigated the clinical relevance of CYP2D6 polymorphisms . METHODS We obtained tumor tissues and isolated DNA from 4861 of 8010 postmenopausal women with hormone receptor-positive breast cancer who enrolled in the r and omized , phase III double-blind Breast International Group ( BIG ) 1 - 98 trial between March 1998 and May 2003 and received tamoxifen and /or letrozole treatment .  Extracted DNA was used for genotyping nine CYP2D6 single-nucleotide polymorphisms using polymerase chain reaction-based methods . Genotype combinations were used to categorize CYP2D6 metabolism phenotypes as poor , intermediate , and extensive metabolizers ( PM , IM , and EM , respectively ; n = 4393 patients ) . Associations of CYP2D6 metabolism phenotypes with breast cancer-free interval ( referred to as recurrence ) and treatment-induced hot flushes according to r and omized endocrine treatment and previous chemotherapy were assessed . Cox proportional hazards models were used to calculate hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) . All statistical tests were two-sided . RESULTS No association between CYP2D6 metabolism phenotypes and breast cancer-free interval was observed among patients who received tamoxifen monotherapy without previous chemotherapy ( P = .35 ) . PM or IM phenotype had a non-statistically significantly reduced risk of breast cancer recurrence compared with EM phenotype ( PM or IM vs EM , HR of recurrence = 0.86 , 95 % CI = 0.60 to 1.24 ) . CYP2D6 metabolism phenotype was associated with tamoxifen-induced hot flushes ( P = .020 ) . Both PM and IM phenotypes had an increased risk of tamoxifen-induced hot flushes compared with EM phenotype ( PM vs EM , HR of hot flushes = 1.24 , 95 % CI = 0.96 to 1.59 ; IM vs EM , HR of hot flushes = 1.23 , 95 % CI = 1.05 to 1.43 ) . CONCLUSIONS CYP2D6 phenotypes of reduced enzyme activity were not associated with worse disease control but were associated with increased hot flushes , contrary to the hypothesis . The results of this study do not support using the presence or absence of hot flushes or the pharmacogenetic testing of CYP2D6 to determine whether to treat postmenopausal breast cancer patients with tamoxifen
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 .