Several molecular tests have been developed to estimate risk of distant recurrence (RDR) and help clinical decision-making regarding adjuvant chemotherapy in early stage BC. The ODX assay is a 21-gene expression profile mainly based on expression levels of genes related to hormone receptor / HER2 signaling and cell proliferation. MS is an immunohistochemistry-based assay measuring the expression of five markers thought to play a significant role in BC biology. Although both validated tests were shown to stratify patients into groups with low, intermediate and high RDR, the tests have not been compared head-to-head in the same cohort of patients and little data is available regarding their correlation with clinicopathologic tumor features. We have previously shown that a proliferative, cellular stroma and inflammatory cells associated with tumor cells may account for unexpected intermediate/high risk estimations based on ODX in low grade BC. In this study we compared the clinicopathologic tumor features with risk estimations by ODX and MS in 106 low grade ER-positive BC. The histologic features of tumors were prospectively determined without knowledge of test results. The tumor stroma was evaluated for increased cellularity and presence of inflammatory cells. Double immunostain for pancytokeratin and Ki67 was performed to assess cell proliferation in cancer vs stromal/inflammatory cells. Based on ODX and MS, among the 106 cases 68, 38 and 0, and 91, 14 and 1 tumors showed low, intermediate and high RDR, respectively. Assessment of the concurrence between the tests to predict low vs intermediate/high RDR showed a kappa value of 0.0541. There was no statistically significant correlation between ODX Recurrence Score (RS) and MS risk index values. We found no correlation between low vs intermediate/high risk estimation by either test and patient age, tumor size, nuclear atypia, mitotic rate, ER and HER2 expression levels. BC with intermediate/high RDR by ODX, but not by MS, showed significantly lower PR expression, increased stromal cellularity and presence of inflammatory cells. Double immunostains showed increased proliferation in stromal/inflammatory cells compared to cancer cells in cases showing intermediate/high RDR by ODX; no such association was seen with regards to MS risk estimations. The ratio of Ki67-positive stromal/inflammatory vs tumor cells >1 had an area under the curve of 0.8929 (p<0.0001) and 0.5026 (p=0.9823) to predict intermediate/high RDR based on ODX and MS, respectively. Cases showing intermediate/high RDR by ODX but low risk by MS were associated with increased stromal cellularity, presence of inflammatory cells and increased numbers of Ki-67 positive stromal/inflammatory cells, compared to cases showing low risk by both assays. Our results suggest that low grade ER-positive BC with increased stromal/inflammatory cell proliferation may show an apparent increased RDR as assessed by ODX, which uses RNA extracted from a mixture of tumor and stromal/inflammatory cells in the assay. MS, which examines cancer cells only (thus, not influenced by stromal and inflammatory cells), may provide a better estimation of likely tumor behavior in low grade BC.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-28.