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 .
TIMP-1 in combination with HER2 and TOP2A for prediction of benefit from adjuvant anthracyclines in high-risk breast cancer patients
HER2 amplification , TOP2A aberrations , and absence of tissue inhibitor of metalloproteinase ( TIMP-1 ) expression in breast carcinomas have been shown to be associated with incremental benefit from anthracycline-containing adjuvant chemotherapy , and this study was undertaken to vali date these findings in a similar , but independent , r and omized clinical trial . TIMP-1 was examined by immunohistochemistry in archival tumor tissue from 403 of 716 premenopausal high-risk patients with known HER2 and TOP2A status who were r and omized to cyclophosphamide , epirubicin , and fluorouracil ( CEF ) or cyclophosphamide , methotrexate , and fluorouracil ( CMF ) in the MA.5 trial . Ninety-eight ( 24 % ) patients had no TIMP-1 staining of tumor cells , 27 % were HER2 amplified , and 18 % were TOP2A aberrant . Forty-four percentage was classified as HT responsive ( HER2 amplified and /or TIMP-1 negative ) and 37 % as 2 T responsive ( TOP2A aberrant and /or TIMP-1 negative ) . There was no heterogeneity in treatment effect of CEF versus CMF according to TIMP-1 . In HT-responsive patients , CEF was superior to CMF with an improved RFS ( adjusted HR , 0.64 ; 95 % CI , 0.42–0.97 ) , but this was not significant for OS ( adjusted HR , 0.66 ; 95 % CI , 0.42–1.04 ) . A significant HT profile versus treatment interaction was detected for OS ( P = 0.03 ) . In 2T-responsive patients , CEF seemed to improve RFS compared to CMF ( adjusted HR , 0.67 ; 95 % CI , 0.43–1.03 ) and improved OS ( adjusted HR , 0.58 ; 95 % CI , 0.36–0.93 ) . A significant 2 T profile versus treatment interaction was detected for OS ( P = 0.01 ) . With this study , we vali date a more substantial reduction in mortality by CEF compared to CMF in patients with an HT- or 2T-responsive profile ; however , we could not show a similarly significant reduction in RFS events , where a benefit of CEF over CMF was found irrespective of TIMP-1 status . Further studies are necessary before the HT and 2 T profiles may be used to direct the use of anthracyclines
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 .