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 .
Topoisomerase II alpha protein and responsiveness of breast cancer to adjuvant chemotherapy with CEF compared to CMF in the NCIC CTG randomized MA.5 adjuvant trial
Overexpression of topoisomerase II protein ( topo 2α ) is postulated to be more closely associated with responsiveness to anthracycline-containing chemotherapy than human epidermal growth factor receptor type 2 ( HER2 ) gene amplification or alterations in the topoisomerase II alpha gene ( TOP2A ) . The authors used tissue microarrays from 477 of 710 premenopausal women with node-positive breast cancer r and omized to CEF or CMF adjuvant chemotherapy in the NCIC Clinical Trials Group Mammary 5 ( MA.5 ) trial . No significant interaction was found between treatment and continuous topo 2α level in either relapse-free ( RFS ) or overall survival ( OS ) . In 136 patients ( 28.5 % ) whose tumors showed topo 2α overexpression by immunohistochemistry based on a cut-off of 13 % , CEF was superior to CMF for RFS ( adjusted HR 0.45 ; 95 % CI 0.25–0.82 ; P = 0.009 ) and OS ( adjusted HR 0.50 ; 95 % CI 0.26–0.96 ; P = 0.04 ) . When tumors lacked topo 2α overexpression , CEF was not superior for RFS ( adjusted HR 0.88 ; 95 % CI 0.64–1.22 ; P = 0.46 ) or OS ( adjusted HR 0.95 ; 95 % CI 0.66–1.38 ; P = 0.80 ) . Interaction between topo 2α and treatment was borderline significant for RFS ( P = 0.04 ) and OS ( P = 0.05 ) and not substantially more significant than between TOP2A gene alteration ( Pinteraction = 0.09 for RFS and 0.02 for OS ) or HER2 overexpression ( Pinteraction = 0.002 for RFS and 0.009 for OS ) . Topo 2α protein overexpression based on the cut-off identified in this study , TOP2A gene alterations and HER2 protein overexpression were each associated with responsiveness to anthracycline-containing chemotherapy . The topo 2α protein analysis was exploratory and will require further validation
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 .