Validation of the OncoMasTR Risk Score in Estrogen Receptor-Positive/HER2-Negative Patients: a TransATAC study

PURPOSE: To test the validity of OncoMasTR Molecular Score (OMm), OMclin1 and OncoMasTR Risk Score (OMclin2) prognostic scores for prediction of distant recurrence (DR) in ER-positive/HER2-negative breast cancer treated with 5 years9 endocrine therapy only and compare their performance with the Oncotype DX Recurrence Score (RS). EXPERIMENTAL DESIGN: OMm incorporates three Master Transcription Regulator genes. OMclin1 combines OMm, tumor size, grade, nodal status; OMclin2 incorporates OMm, tumor size, nodal status. OMclin1 and OMclin2 were evaluated for 646 postmenopausal patients with ER-positive/HER2-negative primary breast cancer with 0-3 involved lymph nodes in TransATAC. Patients were randomised to 5 years9 anastrozole or tamoxifen without chemotherapy. RS was available in all cases. We used likelihood ratio-χ2, C-index, Kaplan-Meier analyses to assess prognostic information. RESULTS: OMm, OMclin1 and OMclin2 were highly prognostic for prediction of DR in years 0-10 among all patients (LRχ2=25.4, 48.7, 45.0, respectively, all P<0.001; C-index=0.67, 0.71, 0.71, respectively), compared to RS (LRχ2=18.8, P<0.001; C-index=0.63). All three scores provided significant additional prognostic value beyond Clinical Treatment Score, Nottingham Prognostic Index, Ki67. OMclin1 and OMclin2 categorised 190 and 267 node-negative patients into low-risk group (DR rates: 2.9%, 4.9%, respectively). In comparison, RS categorised 296 node-negative patients as low-risk, 128 patients as intermediate-risk (DR rate: 6.6%, 17.3%, respectively). CONCLUSIONS: OMm, OMclin1 and OMclin2 were highly prognostic for early and late DR in women with early-stage ER-positive breast cancer receiving 5 years9 endocrine therapy. In TransATAC OMclin1 and the OncoMasTR Risk Score (OMclin2) were superior to RS in identifying patients at increased risk of DR.