Journal Article
. 2019 Jun;8(9).
doi: 10.1002/cam4.2323.

Risk stratification of ER-positive breast cancer patients: A multi-institutional validation and outcome study of the Rochester Modified Magee algorithm (RoMMa) and prediction of an Oncotype DX® recurrence score <26

Bradley M Turner 1 Mary Ann Gimenez-Sanders 2 Armen Soukiazian 3 Andrea C Breaux 2 Kristin Skinner 4 Michelle Shayne 5 Nyrie Soukiazian 6 Marilyn Ling 7 David G Hicks 8 
Affiliations
  • PMID: 31199586
  •     58 References
  •     5 citations

Abstract

The skyrocketing cost of health-care demands that we question when to use multigene assay testing in the planning of treatment for breast cancer patients. A previously published algorithmic model gave recommendations for which cases to send out for Oncotype DX® (ODX) testing. This study is a multi-institutional validation of that algorithmic model in 620 additional estrogen receptor positive breast cancer cases, with outcome data on 310 cases, named in this study as the Rochester Modified Magee algorithm (RoMMa). RoMMa correctly predicted 85% (140/164) and 100% (17/17) of cases to have a low- or high-risk ODX recurrence score, respectively, consistent with the original publication. Applying our own risk stratification criteria, in patients who received appropriate hormonal therapy, only one of the 45 (2.0%) patients classified as low risk by our original algorithm have been associated with a breast cancer recurrence over 5-10 years of follow-up. Eight of 116 (7.0%) patients classified as low risk by ODX have been associated with a breast cancer recurrence with up to 11 years of follow-up. In addition, 524 of 537 (98%) cases from our total population (n = 903) with an average modified Magee score ≤18 had an ODX recurrence score <26. Patients with an average modified Magee score ≤18 or >30 may not need to be sent out for ODX testing. By avoiding these cases sending out for ODX testing, the potential cost savings to the health-care system in 2018 are estimated to have been over $100,000,000.

Keywords: ER+ breast cancer; Oncotype DX®; RoMMa; algorithm; recurrence.

Proliferation (Ki-67 and phosphohistone H3) and oncotype DX recurrence score in estrogen receptor-positive breast cancer.
Daron J Williams, Cynthia Cohen, +3 authors, Amy L Adams.
Appl Immunohistochem Mol Morphol, 2011 Feb 08; 19(5). PMID: 21297447
Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer.
Soonmyung Paik, Gong Tang, +11 authors, Norman Wolmark.
J Clin Oncol, 2006 May 25; 24(23). PMID: 16720680
Highly Cited.
The value of algorithms predicting the Oncotype DX recurrence score should not be underestimated!
Bradley Turner, Ping Tang, David Hicks.
Breast Cancer Res Treat, 2017 Apr 15; 164(1). PMID: 28409240
Use of Oncotype DX in Women with Node-Positive Breast Cancer.
Naoko Ishibe, Sheri Schully, Andrew Freedman, Scott David Ramsey.
PLoS Curr, 2011 Oct 11; 3. PMID: 21984342    Free PMC article.
Impact of breast cancer subtypes and treatment on survival: an analysis spanning two decades.
Reina Haque, Syed A Ahmed, +6 authors, Michael F Press.
Cancer Epidemiol Biomarkers Prev, 2012 Sep 20; 21(10). PMID: 22989461    Free PMC article.
IHC4 score plus clinical treatment score predicts locoregional recurrence in early breast cancer.
Roopa Lakhanpal, Ivana Sestak, +6 authors, Angela Rezo.
Breast, 2016 Aug 09; 29. PMID: 27498128
Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications.
T Sørlie, C M Perou, +14 authors, A L Børresen-Dale.
Proc Natl Acad Sci U S A, 2001 Sep 13; 98(19). PMID: 11553815    Free PMC article.
Highly Cited.
Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up.
C W Elston, I O Ellis.
Histopathology, 1991 Nov 01; 19(5). PMID: 1757079
Highly Cited.
Comparison of Oncotype DX With Modified Magee Equation Recurrence Scores in Low-Grade Invasive Carcinoma of Breast.
Yanjun Hou, Debra L Zynger, Xiaoxian Li, Zaibo Li.
Am J Clin Pathol, 2017 Sep 14; 148(2). PMID: 28898988
Reconsidering "low-risk" criteria for breast cancer recurrence in hormone positive patients.
Armen Soukiazian, David G Hicks, Bradley M Turner.
Breast J, 2019 Apr 12; 25(3). PMID: 30972823
Gene expression profiling and expanded immunohistochemistry tests to guide the use of adjuvant chemotherapy in breast cancer management: a systematic review and cost-effectiveness analysis.
S Ward, A Scope, +4 authors, L Wyld.
Health Technol Assess, 2013 Oct 04; 17(44). PMID: 24088296    Free PMC article.
Systematic Review.
A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer.
Soonmyung Paik, Steven Shak, +12 authors, Norman Wolmark.
N Engl J Med, 2004 Dec 14; 351(27). PMID: 15591335
Highly Cited.
Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis.
Christos Sotiriou, Pratyaksha Wirapati, +17 authors, Mauro Delorenzi.
J Natl Cancer Inst, 2006 Feb 16; 98(4). PMID: 16478745
Highly Cited.
Optimizing the Use of Gene Expression Profiling in Early-Stage Breast Cancer.
Hyun-Seok Kim, Christopher B Umbricht, +22 authors, Leslie Cope.
J Clin Oncol, 2016 Dec 22; 34(36). PMID: 27998227    Free PMC article.
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.
Rohit Bhargava, Beth Z Clark, David J Dabbs.
Am J Clin Pathol, 2018 Nov 06; 151(3). PMID: 30395177    Free PMC article.
Clinical utility of gene-expression profiling in women with early breast cancer: an overview of systematic reviews.
Michael Marrone, Alison Stewart, W David Dotson.
Genet Med, 2014 Dec 05; 17(7). PMID: 25474343    Free PMC article.
Review.
Validation of the IHC4 Breast Cancer Prognostic Algorithm Using Multiple Approaches on the Multinational TEAM Clinical Trial.
John M S Bartlett, Jason Christiansen, +10 authors, Daniel W Rea.
Arch Pathol Lab Med, 2015 Dec 31; 140(1). PMID: 26717057
Progress in implementing HER2 testing guidelines.
Patrick L Fitzgibbons, David G Hicks.
Arch Pathol Lab Med, 2014 Jul 01; 138(7). PMID: 24978910
Gene expression profiling predicts clinical outcome of breast cancer.
Laura J van 't Veer, Hongyue Dai, +13 authors, Stephen H Friend.
Nature, 2002 Feb 02; 415(6871). PMID: 11823860
Highly Cited.
Impact of Oncotype DX on treatment decisions in ER-positive, node-negative breast cancer with histologic correlation.
Julianne R Biroschak, Gordon F Schwartz, +4 authors, Sun Yong Lee.
Breast J, 2013 Apr 26; 19(3). PMID: 23614365
A lower Allred score for progesterone receptor is strongly associated with a higher recurrence score of 21-gene assay in breast cancer.
Ping Tang, Jianmin Wang, +9 authors, Gary Lyman.
Cancer Invest, 2010 Aug 10; 28(9). PMID: 20690804
Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease.
Giampaolo Bianchini, Justin M Balko, +2 authors, Luca Gianni.
Nat Rev Clin Oncol, 2016 Oct 19; 13(11). PMID: 27184417    Free PMC article.
Highly Cited. Review.
Molecular portraits of human breast tumours.
C M Perou, T Sørlie, +15 authors, D Botstein.
Nature, 2000 Aug 30; 406(6797). PMID: 10963602
Highly Cited.
Prognostic value of a combined estrogen receptor, progesterone receptor, Ki-67, and human epidermal growth factor receptor 2 immunohistochemical score and comparison with the Genomic Health recurrence score in early breast cancer.
Jack Cuzick, Mitch Dowsett, +10 authors, John F Forbes.
J Clin Oncol, 2011 Oct 13; 29(32). PMID: 21990413
Highly Cited.
Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer.
Aleix Prat, Joel S Parker, +5 authors, Charles M Perou.
Breast Cancer Res, 2010 Sep 04; 12(5). PMID: 20813035    Free PMC article.
Highly Cited.
Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer.
Joseph A Sparano, Robert J Gray, +27 authors, George W Sledge.
N Engl J Med, 2018 Jun 05; 379(2). PMID: 29860917    Free PMC article.
Highly Cited.
Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update.
Antonio C Wolff, M Elizabeth H Hammond, +19 authors, College of American Pathologists.
Arch Pathol Lab Med, 2013 Oct 09; 138(2). PMID: 24099077    Free PMC article.
Highly Cited.
Pathologic diagnosis, immunohistochemistry, multigene assays and breast cancer treatment: progress toward "precision" cancer therapy.
D G Hicks, B Turner.
Biotech Histochem, 2014 Dec 02; 90(2). PMID: 25434396
Review.
Prospective Validation of a 21-Gene Expression Assay in Breast Cancer.
Joseph A Sparano, Robert J Gray, +28 authors, George W Sledge.
N Engl J Med, 2015 Sep 29; 373(21). PMID: 26412349    Free PMC article.
Highly Cited.
Economic evaluation of genomic test-directed chemotherapy for early-stage lymph node-positive breast cancer.
Peter S Hall, Christopher McCabe, Robert C Stein, David Cameron.
J Natl Cancer Inst, 2011 Dec 06; 104(1). PMID: 22138097
Population-Based Study to Determine the Health System Costs of Using the 21-Gene Assay.
Nicole Mittmann, Craig C Earle, +4 authors, Mark N Levine.
J Clin Oncol, 2017 Dec 02; 36(3). PMID: 29193984
Ki 67 is a major, but not the sole determinant of Oncotype Dx recurrence score.
S Sahebjam, R Aloyz, +6 authors, L C Panasci.
Br J Cancer, 2011 Oct 06; 105(9). PMID: 21970880    Free PMC article.
Cost-Effectiveness Analyses of the 21-Gene Assay in Breast Cancer: Systematic Review and Critical Appraisal.
Shi-Yi Wang, Weixiong Dang, +3 authors, Cary P Gross.
J Clin Oncol, 2018 Apr 17; 36(16). PMID: 29659329    Free PMC article.
Systematic Review.
An international study to increase concordance in Ki67 scoring.
Mei-Yin C Polley, Samuel C Y Leung, +28 authors, Torsten O Nielsen.
Mod Pathol, 2015 Feb 24; 28(6). PMID: 25698062
Highly Cited.
Economic evaluation of the 21-gene signature (Oncotype DX) in lymph node-negative/positive, hormone receptor-positive early-stage breast cancer based on Japanese validation study (JBCRG-TR03).
Masahide Kondo, Shu-Ling Hoshi, +2 authors, Masakazu Toi.
Breast Cancer Res Treat, 2010 Nov 18; 127(3). PMID: 21082239
Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline.
Lyndsay N Harris, Nofisat Ismaila, +11 authors, American Society of Clinical Oncology.
J Clin Oncol, 2016 Feb 10; 34(10). PMID: 26858339    Free PMC article.
Highly Cited. Review.
Clinical and biologic features of triple-negative breast cancers in a large cohort of patients with long-term follow-up.
L Malorni, P B Shetty, +6 authors, G Arpino.
Breast Cancer Res Treat, 2012 Nov 06; 136(3). PMID: 23124476    Free PMC article.
Nottingham-defined mitotic score: comparison with visual and image cytometric phosphohistone H3 labeling indices and correlation with Oncotype DX recurrence score.
Blazej Zbytek, Cynthia Cohen, +3 authors, Amy L Adams.
Appl Immunohistochem Mol Morphol, 2012 Apr 13; 21(1). PMID: 22495373
Routine pathologic parameters can predict Oncotype DX recurrence scores in subsets of ER positive patients: who does not always need testing?
K H Allison, P L Kandalaft, +2 authors, A M Gown.
Breast Cancer Res Treat, 2011 Mar 04; 131(2). PMID: 21369717
Impact of 21-Gene Expression Assay on Staging Estrogen Receptor-Positive HER2-Negative Breast Cancer.
Andrea Breaux, Bradley Turner, +4 authors, Mary Ann Sanders.
Clin Breast Cancer, 2018 Dec 05; 19(1). PMID: 30509870
Using the Modified Magee Equation to Identify Patients Unlikely to Benefit From the 21-Gene Recurrence Score Assay (Oncotype DX Assay).
Yanjun Hou, Gary Tozbikian, Debra L Zynger, Zaibo Li.
Am J Clin Pathol, 2017 Apr 28; 147(6). PMID: 28449064
American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer.
Antonio C Wolff, M Elizabeth H Hammond, +22 authors, College of American Pathologists.
J Clin Oncol, 2006 Dec 13; 25(1). PMID: 17159189
Highly Cited.
Semi-quantitative immunohistochemical assay versus oncotype DX(®) qRT-PCR assay for estrogen and progesterone receptors: an independent quality assurance study.
James A Kraus, David J Dabbs, Sushil Beriwal, Rohit Bhargava.
Mod Pathol, 2012 Feb 04; 25(6). PMID: 22301704
Molecular evolution of breast cancer.
Peter T Simpson, Jorge S Reis-Filho, Theodora Gale, Sunil R Lakhani.
J Pathol, 2005 Jan 11; 205(2). PMID: 15641021
Highly Cited. Review.
Impact of progesterone receptor semiquantitative immunohistochemical result on Oncotype DX recurrence score: a quality assurance study of 1074 cases.
Beth Z Clark, David J Dabbs, Kristine L Cooper, Rohit Bhargava.
Appl Immunohistochem Mol Morphol, 2012 Oct 13; 21(4). PMID: 23060300
Prediction of the Oncotype DX recurrence score: use of pathology-generated equations derived by linear regression analysis.
Molly E Klein, David J Dabbs, +4 authors, Rohit Bhargava.
Mod Pathol, 2013 Mar 19; 26(5). PMID: 23503643    Free PMC article.
Impact of a 21-gene RT-PCR assay on treatment decisions in early-stage breast cancer: an economic analysis based on prognostic and predictive validation studies.
Gary H Lyman, Leon E Cosler, Nicole M Kuderer, John Hornberger.
Cancer, 2007 Feb 22; 109(6). PMID: 17311307
Pathologic diagnosis of breast cancer patients: evolution of the traditional clinical-pathologic paradigm toward "precision" cancer therapy.
B M Turner, D G Hicks.
Biotech Histochem, 2017 Mar 21; 92(3). PMID: 28318327
Can features evaluated in the routine pathologic assessment of lymph node-negative estrogen receptor-positive stage I or II invasive breast cancer be used to predict the Oncotype DX recurrence score?
Jena Auerbach, Mimi Kim, Susan Fineberg.
Arch Pathol Lab Med, 2010 Nov 04; 134(11). PMID: 21043825
Risk stratification of ER-positive breast cancer patients: A multi-institutional validation and outcome study of the Rochester Modified Magee algorithm (RoMMa) and prediction of an Oncotype DX® recurrence score <26.
Bradley M Turner, Mary Ann Gimenez-Sanders, +6 authors, David G Hicks.
Cancer Med, 2019 Jun 15; 8(9). PMID: 31199586    Free PMC article.
Economic implications of 21-gene breast cancer risk assay from the perspective of an Israeli-managed health-care organization.
Shmuel H Klang, Ariel Hammerman, +3 authors, John Hornberger.
Value Health, 2010 Apr 24; 13(4). PMID: 20412544
Use of modified Magee equations and histologic criteria to predict the Oncotype DX recurrence score.
Bradley M Turner, Kristin A Skinner, +6 authors, David G Hicks.
Mod Pathol, 2015 May 02; 28(7). PMID: 25932962
Molecular pathology of breast cancer: what a pathologist needs to know.
Kimberly H Allison.
Am J Clin Pathol, 2012 Nov 20; 138(6). PMID: 23161709
Is the Oncotype DX assay necessary in strongly estrogen receptor-positive breast cancers?
Jenny J Lee, Jeannie Shen.
Am Surg, 2011 Dec 01; 77(10). PMID: 22127090
Economic analysis of targeting chemotherapy using a 21-gene RT-PCR assay in lymph-node-negative, estrogen-receptor-positive, early-stage breast cancer.
John Hornberger, Leon E Cosler, Gary H Lyman.
Am J Manag Care, 2005 May 19; 11(5). PMID: 15898220
Assessment of the contribution of the IHC4+C score to decision making in clinical practice in early breast cancer.
S Barton, L Zabaglo, +6 authors, M Dowsett.
Br J Cancer, 2012 Apr 26; 106(11). PMID: 22531639    Free PMC article.
American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer.
M Elizabeth H Hammond, Daniel F Hayes, +29 authors, Antonio C Wolff.
J Clin Oncol, 2010 Apr 21; 28(16). PMID: 20404251    Free PMC article.
Highly Cited. Systematic Review.
Multigene assays and molecular markers in breast cancer: systematic review of health economic analyses.
Roman Rouzier, Paolo Pronzato, +3 authors, William J Valentine.
Breast Cancer Res Treat, 2013 Jun 01; 139(3). PMID: 23722312    Free PMC article.
Systematic Review.
The healthcare value of the Magee Decision Algorithm™: use of Magee Equations™ and mitosis score to safely forgo molecular testing in breast cancer.
Rohit Bhargava, Beth Z Clark, +2 authors, David J Dabbs.
Mod Pathol, 2020 Mar 24; 33(8). PMID: 32203092    Free PMC article.
Integrated Multiparametric Radiomics and Informatics System for Characterizing Breast Tumor Characteristics with the OncotypeDX Gene Assay.
Michael A Jacobs, Christopher B Umbricht, +5 authors, Antonio C Wolff.
Cancers (Basel), 2020 Oct 01; 12(10). PMID: 32992569    Free PMC article.
How to Predict Metastasis in Luminal Breast Cancer? Current Solutions and Future Prospects.
Sylwia Tabor, Małgorzata Szostakowska-Rodzos, Anna Fabisiewicz, Ewa A Grzybowska.
Int J Mol Sci, 2020 Nov 14; 21(21). PMID: 33182512    Free PMC article.
Review.
Risk stratification of ER-positive breast cancer patients: A multi-institutional validation and outcome study of the Rochester Modified Magee algorithm (RoMMa) and prediction of an Oncotype DX® recurrence score <26.
Bradley M Turner, Mary Ann Gimenez-Sanders, +6 authors, David G Hicks.
Cancer Med, 2019 Jun 15; 8(9). PMID: 31199586    Free PMC article.
Magee Equations™ and response to neoadjuvant chemotherapy in ER+/HER2-negative breast cancer: a multi-institutional study.
Rohit Bhargava, Nicole N Esposito, +11 authors, David J Dabbs.
Mod Pathol, 2020 Jul 15; 34(1). PMID: 32661297