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 estrogen receptor (ER)-positive/HER2-negative breast cancer treated with 5 years' 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, and nodal status; OMclin2 incorporates OMm, tumor size, and 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 randomized to 5 years' anastrozole or tamoxifen without chemotherapy. RS was available in all cases. We used likelihood ratio- , C-index, and 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 [likelihood ratio (LR)- = 25.4, 48.7, and 45.0, respectively, all < 0.001; C-index = 0.67, 0.71, and 0.71, respectively], compared with RS (LR- = 18.8; < 0.001; C-index = 0.63). All three scores provided significant additional prognostic value beyond clinical treatment score, Nottingham Prognostic Index, and Ki67. OMclin1 and OMclin2 categorized 190 and 267 node-negative patients as low risk (DR rates: 2.9% and 4.9%, respectively). In comparison, RS categorized 296 node-negative patients as low-risk and 128 patients as intermediate-risk (DR rate: 6.6% and 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 years' endocrine therapy. In TransATAC, OMclin1 and the OncoMasTR Risk Score (OMclin2) were superior to RS in identifying patients at increased risk of DR.