Abstract P6-07-02: Prediction of oncotype DX® recurrence score using pathology generated equations

Abstract

Abstract BACKGROUND: Oncotype DX® is a quantitative reverse transcription polymerase chain reaction based assay that has been shown to have prognostic and predictive value in estrogen receptor (ER) positive breast cancers. The result is reported as a recurrence score (RS) ranging from 0–100, divided into low risk (<18), intermediate risk (18–30), and high risk (≥31) categories. Prior studies have shown that RS is influenced by ER and progesterone receptor (PR) expression, HER2 status, proliferation index, and tumor grade. Our pilot study showed that RS can be predicted by an equation incorporating standard morpho-immunohistologic variables (referred to as Original Magee Equation; Mod Pathol. 2008;21:1255–1261). METHODS: Using a dataset of 817 cases, we formulated three additional equations to predict the RS category for an independent set of 255 cases. Three models were built based on different hypotheses and data availability and are represented below. New Magee Equation 1 (nME1): RS = 15.31385 + Nottingham score*1.4055+ ER H-score*(−0.01924) + PR H-score*(−0.02925) + (0 for HER2 negative, 0.77681 for equivocal, 11.58134 for HER2 positive) + Tumor size*0.78677 + KI67 index*0.13269. New Magee Equation 2 (nME2): RS = 18.8042+ Nottingham score*2.34123 + ER H-score*(−0.03749) + PR H-score*(−0.03065) + (0 for HER2 negative, 1.82921 for equivocal, 11.51378 for HER2 positive) + Tumor size*0.04267. New Magee Equation 3 (nME3): RS = 24.30812+ ER H-score*(−0.02177) + PR H-score*(−0.02884) + (0 for HER2 negative, 1.46495 for equivocal, 12.75525 for HER2 positive) + KI-67*0.18649. RESULTS: The concordance between the risk category of oncotype DX® and our equations was 55.8%, 59.4%, and 54.4% for nME1, nME2, and nME3 respectively. With exclusion of the intermediate risk categories for both the actual RS and estimated RS, the concordance for each equation increased to more than 95%, reflecting the very low two step discordance (100% {76/76}, 98.6% {75/76}, and 98.7% {79/80} for nME1, nME2, and nME3 respectively). Even when the estimated RS fell in the intermediate category with any of the equations, the actual RS was either intermediate or low in more than 85% of the cases. The Pearson correlation coefficient between estimated and actual RS was similar for each of the equations (0.61661, 0.60386 and 0.59407 for nME1, nME2 and nME3, respectively). CONCLUSIONS: Any of the 3 equations can be used to estimate the RS depending on available data. If the estimated RS is clearly high or low, the oncologists should not expect a dramatically different result from oncotype DX®, and the oncotype DX® test may not be needed. Conversely, an oncotype DX® result that is dramatically different from what is expected based on standard morpho-immunohistologic variables should be thoroughly investigated. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-07-02.