Magee Equations^{™} for Estimating Oncotype DX^{®} Recurrence Score
Magee Equations^{™} Input and Results
Insert values in their respective fields. Once all necessary fields have valid values, all three Magee Equations will automatically calculate.
Nottingham Score 3 to 9 |
ER H-Score 0 to 300 |
PR H-Score 0 to 300 |
HER2 |
Tumor Size cm |
KI-67 Percentage % |
Equation 1 Result |
Equation 2 Result |
Equation 3 Result |
Background
Oncotype DX^{®} (Genomic Health Inc. Redwood City, CA), is a commercial assay, frequently used by oncologists for making chemotherapy decisions. It is a quantitative reverse transcription polymerase chain reaction based assay, used to estimate the risk of distant recurrence for patients with ER positive, lymph node negative breast cancers. It is reported as a numerical score (recurrence score or RS) ranging from 0-100. At test inception, the risk categories were defined as low risk (LR; <18), intermediate risk (IR; 18-30), and high risk (HR; >e;31). In the TAILORx trial, endocrine therapy was non-inferior to chemoendocrine therapy in the analysis of invasive disease-free survival for patients (age >50 years) with RS of 11-25. In a pilot proof of principle study from this institution, it was reported that standard histopathologic factors and immunohistochemical markers can be used to estimate the recurrence score (original Magee equation; Mod Pathol. 2008;21:1255-1261). Subsequently, new Magee Equations were derived using a much larger database of over 800 cases that were sent for clinical oncotype DX^{®} testing to Genomic Health as per oncologists’ request. These new Magee Equations were validated on a separate set of over 200 cases, again sent for clinical oncotype DX^{®} testing to Genomic Health as per oncologists’ request.How the New Magee Equations Were Derived
Multiple linear regression analysis was performed to model the prediction of the oncotype DX^{®} RS by Nottingham Score (range 3-9), Ki-67 labeling index (0-100), tumor size (in cm.), H-scores (range: 0-300) for ER and PR, and HER2 status (negative, equivocal or positive). Three models were built based on different hypotheses and data availability. The first regression model included all available parameters (including Ki-67 index) for prediction of oncotype DX^{®} RS. The second regression model was similar to the first but did not include Ki-67. The third regression model included only semi-quantitative immunohistochemical expression levels for ER, PR, HER2 and Ki-67. These 3 equations are now commonly referred to as the Magee Equations^{™}.How to Use the Equations
All the required data is generally present in the surgical pathology report. The hormone receptor results will require the semi-quantitative H-score. If not reported initially, this can be easily calculated by the case pathologist by reviewing the immunohistochemical (IHC) stain slides. H-scores are calculated based on percentage of positive cells showing none, weak, moderate, or strong staining intensity. The score is given as the sum of the percent staining multiplied by an ordinal value corresponding to the intensity level (0=none, 1=weak, 2=moderate, 3=strong). With four intensity levels, the resulting score ranges from 0 (no staining in the tumor) to 300 (diffuse intense staining). For e.g. a tumor showing no staining in 10% cells, weak staining in 30% cells, moderate staining in 40% cells, and strong staining in 20% cells; the H-score will be calculated as follows: (0x10)+(1x30)+(2x40)+(3x20)=170. HER2 status (for purposes of the Magee Equations) should be classified as shown below.- HER2 negative: HER2 IHC score 0, IHC score 1+, and IHC score 2+ with HER2 copies per cell less than 4 by FISH
- HER2 positive: HER2 IHC score of 3+, and HER2 IHC score of 2+ with HER2 copies per cell of 6 or more by FISH
- HER2 equivocal: HER2 IHC score of 2+ with HER2 copies per cell of 4 to less than 6 by FISH
An algorithmic approach to utilize molecular testing in primary breast cancer is discussed in the following publication: Bhargava R, Clark BZ, Dabbs DJ. Breast Cancers With Magee Equation Score of Less Than 18, or 18-25 and Mitosis Score of 1, Do Not Require Oncotype DX Testing: A Value Study. Am J Clin Pathol. 2018 Nov 2. PMID: 30395177.
Reference
Klein ME, Dabbs DJ, Shuai Y, Brufsky AM, Jankowitz R, Puhalla SL, Bhargava R. Prediction of the Oncotype DX^{®} Recurrence Score: Use of Pathology Generated Equations Derived by Linear Regression Analysis. Mod Pathol. 2013. 2013.26:658-664. PMID: 23503643.Internal Publications
- Flanagan MB, Dabbs DJ, Brufsky AM, Beriwal S, Bhargava R. Histopathologic variables predict Oncotype DX recurrence score. Mod Pathol. 2008 Oct;21(10):1255-61. PMID: 18360352.
- Klein ME, Dabbs DJ, Shuai Y, Brufsky AM, Jankowitz R, Puhalla SL, Bhargava R. Prediction of the Oncotype DX^{®} Recurrence Score: Use of Pathology Generated Equations Derived by Linear Regression Analysis. Mod Pathol. 2013.26:658-664. PMID: 23503643.
- Bhargava R, Dabbs DJ. Magee equations and Oncotype DX^{®} - a perspective. Breast Cancer Res Treat. 2017 Jul;164(1):245-246. PMID: 28393310.
- Farrugia DJ, et al. Magee Equation 3 predicts pathologic response to neoadjuvant systemic chemotherapy in estrogen receptor positive, HER2 negative/equivocal breast tumors. Mod Pathol. 2017 Aug;30(8):1078-1085. PMID: 28548119.
- Dabbs DJ, Clark BZ, Serdy K, Onisko A, Brufsky AM, Smalley S, Perkins S, Bhargava R. Pathologist's health-care value in the triage of Oncotype DX^{®} testing: a value-based pathology study of tumour biology with outcomes. Histopathology. 2018 Oct; 73(4): 692-700. PMID: 29920746.
- Bhargava R, Clark BZ, Dabbs DJ. Breast Cancers With Magee Equation Score of Less Than 18, or 18-25 and Mitosis Score of 1, Do Not Require Oncotype DX Testing: A Value Study. Am J Clin Pathol. 2019;151:316-323. PMID: 30395177.
External Publications
- Turner BM, et al. Use of modified Magee equations and histologic criteria to predict the Oncotype DX recurrence score. Mod Pathol. 2015 Jul;28(7):921-31. PMID: 25932962.
- Chen YY, Tseng LM, Yang CF, Lien PJ, Hsu CY. Adjust cut-off values of immunohistochemistry models to predict risk of distant recurrence in invasive breast carcinoma patients. J Chin Med Assoc. 2016 Dec;79(12):649-655. PMID: 27595437.
- Hou Y, Zynger DL, Li X, Li Z. Comparison of Oncotype DX With Modified Magee Equation Recurrence Scores in Low-Grade Invasive Carcinoma of Breast. Am J Clin Pathol. 2017 Aug 1;148(2):167-172. PMID: 28898988.
- Harowicz MR, Robinson TJ, Dinan MA, Saha A, Marks JR, Marcom PK, Mazurowski MA. Algorithms for prediction of the Oncotype DX recurrence score using clinicopathologic data: a review and comparison using an independent dataset. Breast Cancer Res Treat. 2017 Feb;162(1):1-10. PMID: 28064383.
- Hou Y, Tozbikian G, Zynger DL, Li Z. Using the Modified Magee Equation to Identify Patients Unlikely to Benefit From the 21-Gene Recurrence Score Assay (Oncotype DX Assay). Am J Clin Pathol. 2017 Jun 1;147(6):541-548. PMID: 28449064.
- Sughayer M, Alaaraj R, Alsughayer A. Applying new Magee equations for predicting the Oncotype Dx recurrence score. Breast Cancer. 2018;25:597-604. PMID: 29691722.
- Walts AE, Mirocha JM, Bose S. Comparison of Magee and Oncotype DX Recurrence Scores in estrogen receptor positive breast cancers. Breast J. 2018;24:951-956. PMID: 30230113.
- Robertson SJ, Ibrahim MFK, Stober C, Hilton J, Kos Z, Mazzarello S, Ramsay T, Fergusson D, Vandermeer L, Mallick R, Arnaout A, Dent SF, Segal R, Sehdev S, Gertler S, Hutton B, Clemons M. Does integration of Magee equations into routine clinical practice affect whether oncologists order the Oncotype DX test? A prospective randomized trial. J Eval Clin Pract. 2019 Jan 23. doi: 10.1111/jep.13094. [Epub ahead of print]. PMID: 30672056.