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 .
Prediction of late distant recurrence in patients with oestrogen-receptor-positive breast cancer: a prospective comparison of the breast-cancer index (BCI) assay, 21-gene recurrence score, and IHC4 in the TransATAC study population.
BACKGROUND Biomarkers to improve the risk-benefit of extended adjuvant endocrine therapy for late recurrence in patients with oestrogen-receptor-positive breast cancer would be clinical ly valuable . We compared the prognostic ability of the  breast-cancer index  ( BCI ) assay , 21-gene recurrence score ( Oncotype DX ) , and an immunohistochemical prognostic model ( IHC4 ) for both early and late recurrence in patients with oestrogen-receptor-positive , node-negative ( N0 ) disease who took part in the Arimidex , Tamoxifen , Alone or in Combination ( ATAC ) clinical trial . METHODS In this prospect i ve comparison study , we obtained archival tumour blocks from the TransATAC tissue bank from all postmenopausal patients with oestrogen-receptor-positive breast cancer from whom the 21-gene recurrence score and IHC4 values had already been derived . We did BCI analysis in matched sample s with sufficient residual RNA using two BCI models-cubic ( BCI-C ) and linear (BCI-L)-using previously vali date d cutoffs . We assessed prognostic ability of BCI for distant recurrence over 10 years ( the primary endpoint ) and compared it with that of the 21-gene recurrence score and IHC4 . We also tested the ability of the assays to predict early ( 0 - 5 years ) and late ( 5 - 10 years ) distant recurrence . To assess the ability of the biomarkers to predict recurrence beyond st and ard clinicopathological variables , we calculated the change in the likelihood-ratio χ(2 ) ( LR-Δχ(2 ) ) from Cox proportional hazards models . FINDINGS Suitable tissue was available from 665 patients with oestrogen-receptor-positive , N0 breast cancer for BCI analysis . The primary analysis showed significant differences in risk of distant recurrence over 10 years in the categorical BCI-C risk groups ( p<0·0001 ) with 6·8 % ( 95 % CI 4·4 - 10·0 ) of patients in the low-risk group , 17·3 % ( 12·0 - 24·7 ) in the intermediate group , and 22·2 % ( 15·3 - 31·5 ) in the high-risk group having distant recurrence . The secondary analysis showed that BCI-L was a much stronger predictor for overall ( 0 - 10 year ) distant recurrence compared with BCI-C ( interquartile HR 2·30 [ 95 % CI 1·62 - 3·27 ] ; LR-Δχ(2)=22·69 ; p<0·0001 ) . When compared with BCI-L , the 21-gene recurrence score was less predictive ( HR 1·48 [ 95 % CI 1·22 - 1·78 ] ; LR-Δχ(2)=13·68 ; p=0·0002 ) and IHC4 was similar ( HR 1·69 [ 95 % CI 1·51 - 2·56 ] ; LR-Δχ(2)=22·83 ; p<0·0001 ) . All further analyses were done with the BCI-L model . In a multivariable analysis , all assays had significant prognostic ability for early distant recurrence ( BCI-L HR 2·77 [ 95 % CI 1·63 - 4·70 ] , LR-Δχ(2)=15·42 , p<0·0001 ; 21-gene recurrence score HR 1·80 [ 1·42 - 2·29 ] , LR-Δχ(2)=18·48 , p<0·0001 ; IHC4 HR 2·90 [ 2·01 - 4·18 ] , LR-Δχ(2)=29·14 , p<0·0001 ) ; however , only BCI-L was significant for late distant recurrence ( BCI-L HR 1·95 [ 95 % CI 1·22 - 3·14 ] , LR-Δχ(2)=7·97 , p=0·0048 ; 21-gene recurrence score HR 1·13 [ 0·82 - 1·56 ] , LR-Δχ(2)=0·48 , p=0·47 ; IHC4 HR 1·30 [ 0·88 - 1·94 ] , LR-Δχ(2)=1·59 , p=0·20 ) . INTERPRETATION BCI-L was the only significant prognostic test for risk of both early and late distant recurrence and identified two risk population s for each timeframe . It could help to identify patients at high risk for late distant recurrence who might benefit from extended endocrine or other therapy . FUNDING Avon Foundation , National Institutes of Health , Breast Cancer Foundation , US Department of Defense Breast Cancer Research Program , Susan G Komen for the Cure , Breakthrough Breast Cancer through the Mary-Jean Mitchell Green Foundation , AstraZeneca , Cancer Research UK , and the National Institute for Health Research Biomedical Research Centre at the Royal Marsden ( London , UK )
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 .