Prediction of Oncotype DX Recurrence Score: Use of Equations Derived by Linear Regression Analysis
Molly E Klein, David J Dabbs, Yongli Shuai, Rohit Bhargava. University of Wisconsin, Madison, WI; Magee-Womens Hospital of UPMC, Pittsburgh, PA; University of Pittsburgh Cancer Institute, Pittsburgh, PA
Background: Oncotype DX® is a quantitative reverse transcription polymerase chain reaction based assay, shown to have prognostic and predictive value in estrogen receptor (ER) positive breast cancers. The Oncotype DX® recurrence score (RS) ranges from 0-100, divided into low, intermediate or high risk categories (LR <18, IR 18-30, HR ≥31). Morpho-immunohistologic correlation studies have shown that RS is heavily influenced by ER and progesterone receptor (PR) H-scores, HER2 status, Ki-67 proliferation index, and tumor grade. Our pilot study of 42 cases (Mod Pathol. 2008;21:1255-1261) showed that RS can be predicted by the following (old Magee equation, oME): RS =13.424 + 5.420*(nuclear grade) + 5.538*(mitotic count) - 0.045*(ER H-score) - 0.030*(PR H-score) + 9.486*(0 for HER2 negative, 1 for positive).
Design: We used a dataset of over 800 cases to formulate three new RS equations, then used each equation to calculate a RS for an independent set of 162 cases.
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 positive) + Tumor size*0.78677 + Ki-67*0.13269.
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 positive) + Tumor size*0.04267.
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 positive) + Ki-67*0.18649.
Results: The concordance between RS category by Oncotype DX® and Magee equations was 54.6% (88/161), 55.7% (87/156), 59.7% (95/159), and 54% (86/159) for oME, nME1, nME2, and nME3 respectively. When the IR category was eliminated, the concordance increased to 95.4% (62/65), 100% (52/52), 98.1% (52/53), and 98.1% (53/54) for oME, nME1, nME2, and nME3 respectively. The mean (median) RS for Oncotype DX® was 20 (19), compared to 17.5 (16) for oME, 19.9 (18.8) for nME1, 19.8 (19.6) for nME2 and 19.3 (18.5) for nME3.
Conclusions: Any of the four equations may be used to calculate a RS, using reported pathologic findings. When the calculated RS is LR or HR, the concordance with the Oncotype DX® RS is very high, and Oncotype DX® testing may even be avoided. Conversely, pathologists should investigate any Oncotype DX® RS that is dramatically different than expected based on pathologic findings, to ensure accuracy of the Oncotype DX® result.
Tuesday, March 20, 2012 8:30 AM
Platform Session: Section B, Tuesday Morning