Comparison of risk stratification of ER-positive, node-negative breast cancer patients by Oncotype DX versus molecular grade index and HOXB13/IL17BR ratio

Abstract

22061 Background: We have previously reported two complementary prognostic markers in breast cancer for predicting risk of recurrence: a molecular grade index (MGI) that recapitulates tumor grade and a gene expression ratio (HOXB13/IL17BR or H/I) that is a marker for estrogen signaling. MGI and H/I represent two distinct prognostic modules in breast cancer. Combined they are a strong predictor of recurrence (Ma et al., ASCO Breast Cancer Symposium, 2007). We conducted a study to compare risk stratification by MGI and H/I within samples for which a previous recurrence score (RS) by Oncotype Dx was reported. Methods: RNA was extracted from formalin-fixed paraffin-embedded sections from all obtainable samples from four institutions in which a RS was reported (78pts total; MGH, 43pts; IU, 19pts; UAB, 13pts; Scripps, 9pts). Real-time RT-PCR assays for MGI and H/I were completed and binary results of low and high for both were determined using pre-defined cutpoints. Three risk groups were categorized as follows: low (low MGI), intermediate (high MGI, low H/I) and high (high MGI, high H/I) as described (Ma et al., ASCO Breast Cancer Symposium, 2007). Risk stratification via MGI + H/I for each sample was compared to previously reported RS's (low, intermediate or high). Results: Overall, risk stratifications by RS versus MGI + H/I were significantly correlated (p = 0.00067). RS's from Oncotype DX were 47% low, 45% intermediate and 8% high. In contrast, risk groups according to MGI + H/I were 70% low, 17% intermediate and 13% high (see table). Conclusions: MGI + H/I produces a smaller group of patients with intermediate risk by re-stratifying a large number of patients with intermediate RS into low and high risk groups. This may allow for more informed treatment decisions by the treating oncologist. Further comparative studies with clinical outcome are required to establish the clinical significance of these different risk stratification methods. Comparison of Risk Stratification MGI + H/I Low MGI + H/I Inter. MGI + H/I High Total RS Low 31 6 0 37 RS Inter. 22 5 8 35 RS High 2 2 2 6 Total 55 13 10 78 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AviaraDx AviaraDx AviaraDx