Abstract P4-07-05: Correlation of a Proliferation Index Combined with Progesterone Receptor to Oncotype DX® in Early Stage ER-Positive Breast Cancer
Authors: Sninsky J , Iverson A , Sanitni C , Sigua C , Anderson S , Broder S , White Jr. 
Published: April 2011

Abstract
Background: Different gene expression sets have been reported to reproducibly assess the metastatic potential of early stage operable breast tumors. Knowledge of the biology-based components of amalgamated expression scores may provide insight into the relative contributions of the cellular processes involved. We sought to compare a composite metastasis score (cMS) consisting of a previously reported Metastasis Score (MS), that serves essentially as a proliferation index, and the progesterone receptor (PR) with the Oncotype DX® Recurrence Score (RS) in a regional cancer center setting.
Methods: We examined sections from 152 blocks collected in the Blumenthal Cancer Center that had Oncotype DX® scores (a commercially available service performed by Genomic Health Inc. (GHI)). The study protocol was approved by the Institutional Review Board of the Blumenthal Cancer Center. ER and PR were initially scored by IHC; HER2 was determined by FISH. RT-PCR multiplex TaqMan assays of a 14-gene Metastasis Score (Tutt et al. (2008)) and a multiplex assay for ER, PR and HER2 (Iverson et al. (2009)) were carried out. A cMS was generated with MS and PR using previously constructed weighting. Risk classification of cMS was based on a single pre-established cut point; GHI recommended cut points were used for categorized Oncotype DX® risk. Correlations were estimated by Pearson's product-moment correlation coefficient; a goodness-of-fit test was used to determine differences in the categorical proportions.
Results: Eighty-nine (59%), 51 (34%), and 12 (8%) of the 152 tumors tested had low, intermediate and high Oncotype DX® Recurrence Scores, respectively. The continuous scores for cMS and RS were correlated (r=0.71). Of the 89 tumors categorized as low risk by RS, 78 (88%) and 11 (12%) were at low and high risk by cMS, respectively; all (12) of the tumors categorized as high risk by RS were high risk by cMS; and of the 51 tumors with intermediate RS, 27 (53%) were categorized as low risk and 24 (47%) as high risk by cMS. Correlations of RT-PCR PR levels with overall RS and cMS scores were 0.70 and 0.71, respectively. The MS had correlations of 0.50 and 0.80 with RS and cMS, respectively. The categorized risk proportions of this patient population differed from those reported by Paik et al. (2004) (p=1.47x10-7). Tumors with HER2 gene amplification by FISH [3/141 (2%)] were under-represented (p=0.016) relative to Paik et al. (2004) [55/715 (8%)]; the proportion of PR negative tumors for Paik et al. [126/668 (19%)] and this study [14/149 (9%)], were also dissimilar (p=0.006).
Conclusions: Despite sharing few genes, the continuous scores for cMS and RS show good correlation. The correlation of PR with these two scores suggests the level of this hormone receptor makes a similar significant contribution to both scores in this patient population. MS was more highly correlated to cMS than RS. Distinguishable features of cMS relative to the amalgamated RS include binary categorization of a continuous score and availability and transparency of discrete and combined scores for the endocrine and proliferation components. Under-representation of HER2- amplified tumors suggests exclusion of this patient group from testing.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-07-05.