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 .
The value of TOP2A gene copy number variation as a biomarker in breast cancer: Update of DBCG trial 89D
Background . Previous analyses of TOP2A and HER2 in the Danish Breast Cancer Coopererative Group ( DBCG ) trial 89D suggested that TOP2A amplifications and possible also deletions are predictive markers for the effect of adjuvant epirubicin in patients with primary breast cancer . We present an up date d and extended statistical analysis , requested for IVD-labeling of TOP2A testing . Material and methods . In the DBCG trial 89D 980 Danish patients were r and omly assigned to nine cycles of intravenous CMF ( cyclophosphamide , methotrexate , and fluorouracil ) or CEF ( cyclophosphamide , epirubicin , and fluorouracil ) . Archival tumor tissue was collected retrospectively from 806 of these patients in a prospect ively design ed , biological sub- study , and was successfully analyzed for TOP2A aberrations and HER2 status in 773 sample s ( 96 % ) . Recurrence-free survival ( RFS ) was the primary endpoint . Results . TOP2A aberrations ( amplifications and deletions ) were significantly associated with shorter RFS ( p<0.0001 ) and overall survival ( OS ) ( p<0.0001 ) . Deleted cases had worse prognosis than amplified cases . In a Cox proportional hazard model TOP2A was an independent prognostic marker for RFS and OS . Patients with amplifications had a 61 % reduction in the risk of an event ( p=0.002 ) and a 51 % reduction in the risk of death ( p=0.01 ) if allocated to CEF compared to 6 % and 10 % in TOP2A normal patients . A similar but non-significant trend ( p=0.08 ) was shown in patients with TOP2A deletions . Clear statistical evidence of a differential benefit , favoring CEF among patients with TOP2A aberrations was found for RFS ( p=0.02 for interaction ) but not for OS ( p=0.14 for interaction ) . Conclusion . In conclusion , this up date d analysis of TOP2A aberrations in DBCG trial 89D suggests a differential benefit of adjuvant chemotherapy in patients with primary breast cancer , favoring treatment with epirubicin in patients with TOP2A amplifications , and perhaps deletions . Additional studies are needed to clarify the exact importance of TOP2A deletions on outcome , but deletions have proven to be associated with a very poor prognosis
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 .