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 .
Clinical validation of the EndoPredict test in node-positive, chemotherapy-treated ER+/HER2− breast cancer patients: results from the GEICAM 9906 trial
Introduction EndoPredict ( EP ) is an RNA-based multigene test that predicts the likelihood of distant recurrence in patients with estrogen receptor-positive ( ER+ ) , human epidermal growth factor receptor 2–negative ( HER2− ) breast cancer ( BC ) who are being treated with adjuvant endocrine therapy .  Herein we report the prospect ive-retrospective clinical validation of EP in the node-positive , chemotherapy-treated , ER+/HER2− BC patients in the GEICAM 9906 trial . Methods The patients ( N = 1,246 ) were treated either with six cycles of fluorouracil , epirubicin and cyclophosphamide ( FEC ) or with four cycles of FEC followed by eight weekly courses of paclitaxel ( FEC-P ) , as well as with endocrine therapy if they had hormone receptor – positive disease . The patients were assigned to EP risk categories ( low or high ) according to prespecified cutoff levels . The primary endpoint in the clinical validation of EP was distant metastasis-free survival ( MFS ) . Metastasis rates were estimated using the Kaplan-Meier method , and multivariate analysis was performed using Cox regression . Results The molecular EP score and the combined molecular and clinical EPclin score were successfully determined in 555 ER+/HER2− tumors from the 800 available sample s in the GEICAM 9906 trial . On the basis of the EP , 25 % of patients ( n = 141 ) were classified as low risk . MFS was 93 % in the low-risk group and 70 % in the high-risk group ( absolute risk reduction = 23 % , hazard ratio ( HR ) = 4.8 , 95 % confidence interval ( CI ) = 2.5 to 9.5 ; P < 0.0001 ) . Multivariate analysis showed that , in this ER+/HER2− cohort , EP results are an independent prognostic parameter after adjustment for age , grade , lymph node status , tumor size , treatment arm , ER and progesterone receptor ( PR ) status and proliferation index ( Ki67 ) . Using the predefined EPclin score , 13 % of patients ( n = 74 ) were assigned to the low-risk group , who had excellent outcomes and no distant recurrence events ( absolute risk reduction vs high-risk group = 28 % ; P < 0.0001 ) . Furthermore , EP was prognostic in premenopausal patients ( HR = 6.7 , 95 % CI = 2.4 to 18.3 ; P = 0.0002 ) and postmenopausal patients ( HR = 3.3 , 95 % CI = 1.3 to 8.5 ; P = 0.0109 ) . There were no statistically significant differences in MFS between treatment arms ( FEC vs FEC-P ) in either the high- or low-risk groups . The interaction test results between the chemotherapy arm and the EP score were not significant . Conclusions EP is an independent prognostic parameter in node-positive , ER+/HER2− BC patients treated with adjuvant chemotherapy followed by hormone therapy . EP did not predict a greater efficacy  of FEC-P compared to FEC alone
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 .