Abstract P3-07-16: Comparing surrogates of oncotype Dx recurrence scores in invasive ductal carcinoma: How complicated does it have to be?

Abstract

Background: The Oncotype DX Recurrence Score (ODX) is commonly used to estimate recurrence risk and chemotherapy benefit in ER positive, node negative breast cancer but is associated with significant cost. The Magee score (MS), a free online calculation using numerical values of commonly assessed pathological features (ER, PR, Her2/neu, and Ki-67), has been validated as an ODX surrogate. This includes the MS using classic H scores (HMagee) or Surrogate H scores derived from total % positive cells and average intensity or our use of Surrogate H scores derived from Allred scores (SMagee). Also Gage et al (2015) used a simple algorithm based on tumor grade, PR >1% and ER>20%. Here we compare three methods of predicting ODX scores. Design: 61 patients from The Ottawa Hospital with ER positive HER2/neu negative invasive ductal carcinoma (IDC), known ODX were assessed. Classic H scores (CH) were assessed using Image analysis. All cases had Ki67 (1000 cell hot spot score), tumor size, grade, and Allred scores available. Surrogate H scores (SH) were derived (average reported intensity x midpoint of reported Allred positive score range or absolute percentage if between 1-10%). The three MS were calculated with CH giving classic MS (HMagee) and with SH giving surrogate scores (SMagee). Each case was also categorized using rules published by Gage (2015): LOW predicted if Low Grade and PR positive (>1%), HIGH predicted if High Grade or Low ER (<20%). Agreement with classic ODX categories of low (<18), intermediate (18-30) and high risk (≥ 31) was assessed. Results: ODX included 35 low, 20 intermediate and 6 high risk (Mean 17.4, sd=10). There was a good correlation between corresponding HMagee and SMagee 1-3(0.820, 0.73, 0.84). Concentrating on the theoretically best MS1 that includes Ki67 and all clinical variables (Table 1); HMagee1 predicted 32 cases as low grade with 78% accuracy and SMagee1 predicted 26 low grade with 92.3% accuracy. Of note, all intermediate ODX predicted low by MS were ODX 18-20. None of the MS falsely predicted high risk in low risk ODX. The one case of high ODX which MS predicted low (false negative) is controversial as an Allred ER&PR 8 tumor gave low ODX PR score. Using SMagee1 in this population would safely leave 32 (52.5%) in the intermediate category. Of note, all intermediate ODX predicted low by MS were borderline ODX 18-20. The Gage algorithm in our population is less useful with higher discordance rate and left 69% in the intermediate category. Table 1TestMagee RiskNODX LowODX IntermediateODX High%DiscordantHMagee1Low (<18)3225/78%7/22%07/22% Moderate(≥18-30)2810/36%15/54%3/11%13/46% High (≥31)1001/1.6%0SMagee1Low (<18)2624/92%1/4%1/4%2/8% Moderate(≥18-30)3211/33%19/58%3/9%14/44% High (≥31)2002/100%0GageLow108/80%1/10%1/10%2/20% Moderate4225/60%16/38%1/2.4%26/62% High92/22%3/33%4/44%5/56% Conclusions: In IDC, while simpler algorithms without proliferation markers do not perform as well; SMagee1 based on Allred, performs at least as well in prediction of ODX as an MS based on classic H score and can potentially save considerable time and money. In our hands the simpler Gage algorithm does not perform as well. Citation Format: Robertson SJ, Petkiewicz SL, Arnaout A, Clemons M, Gravel DH, Pond GR. Comparing surrogates of oncotype Dx recurrence scores in invasive ductal carcinoma: How complicated does it have to be?. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-16.

Does integration of Magee equations into routine clinical practice affect whether oncologists order the Oncotype DX test? A prospective randomized trial

“…Third, given the fact that Magee Equation calculations require the labour‐intensive H‐scores, we have been using our own surrogate for H‐score calculation. With respect to the Magee score as calculated in our institution, we have previously shown that at our institution, there was a strong correlation of ODX Recurrence Scores and Magee Equations calculated using percentage Ki67 score (based on image‐assisted hotspot counts of 1000 cells) and an estimated H‐score for ER and PR . Finally, this study was performed before the results of the TAILORx trial were presented, which has somewhat defined management for the intermediate risk group .…”

“…The role of these equations, like ODX, is limited in patients in the intermediate risk group, in whom the benefit of chemotherapy remains unconfirmed . However, if the estimated recurrence score is in the high or low categories, Magee Equations are predictive of the ODX recurrence score category with greater than 95% certainty,and thus, additional ODX testing may not be needed . Indeed, we have shown that estimated recurrence score (using Magee Equations) in the intermediate category means that the actual ODX recurrence score category will be either intermediate or low approximately 85% of the time …”

“…A limitation of the standard Magee Equations is that it uses the H‐score for ER and PR expression, which is labour intensive if done manually, or requires specialized software if done by automated image analysis. We have previously compared Magee scores calculated with standard H‐score (image‐assisted assessment of 1000 cells) with a surrogate H‐score approximation for ER and PR using components of the routinely reported Allred score . For both invasive ductal and invasive lobular carcinoma, we found that the simplified Magee scores using the surrogate ER and PR H‐scores and an image‐assisted hotspot Ki67 count of 1000 cells closely correlated with the overall ODX score .…”

“…All counted fields are saved with digital markups of the cells counted positive or negative. This methodology when used in Magee Equations calculations has been previously validated as highly correlated with ODX recurrence scores for both ductal and lobular invasive ER positive node negative disease.…”

“…We have previously compared Magee scores calculated with standard H‐score (image‐assisted assessment of 1000 cells) with a surrogate H‐score approximation for ER and PR using components of the routinely reported Allred score . For both invasive ductal and invasive lobular carcinoma, we found that the simplified Magee scores using the surrogate ER and PR H‐scores and an image‐assisted hotspot Ki67 count of 1000 cells closely correlated with the overall ODX score . For both ER and PR Allred intensity, proportion and overall scores were measured.…”