Journal Article
. 2011 Oct;29(33).
doi: 10.1200/JCO.2011.35.3714.

Risk of recurrence and chemotherapy benefit for patients with node-negative, estrogen receptor-positive breast cancer: recurrence score alone and integrated with pathologic and clinical factors

Gong Tang 1 Jack Cuzick  Joseph P Costantino  Mitch Dowsett  John F Forbes  Michael Crager  Eleftherios P Mamounas  Steven Shak  Norman Wolmark  
Affiliations
  • PMID: 22010013
  •     13 References
  •     48 citations

Abstract

Purpose: The 21-gene breast cancer assay recurrence score (RS) is widely used for assessing recurrence risk and predicting chemotherapy benefit in patients with estrogen receptor (ER) -positive breast cancer. Pathologic and clinical factors such as tumor size, grade, and patient age also provide independent prognostic utility. We developed a formal integration of these measures and evaluated its prognostic and predictive value.

Patients And Methods: From the National Surgical Adjuvant Breast and Bowel (NSABP) B-14 and translational research cohort of the Arimidex, Tamoxifen Alone or in Combination (TransATAC) studies, we included patients who received hormonal monotherapy, had ER-positive tumors, and RS and traditional clinicopathologic factors assessed (647 and 1,088, respectively). Individual patient risk assessments from separate Cox models were combined using meta-analysis to form an RS-pathology-clinical (RSPC) assessment of distant recurrence risk. Risk assessments by RS and RSPC were compared in node-negative (N0) patients. RSPC was compared with RS for predicting chemotherapy benefit in NSABP B-20.

Results: RSPC had significantly more prognostic value for distant recurrence than did RS (P < .001) and showed better separation of risk in the study population. RSPC classified fewer patients as intermediate risk (17.8% v 26.7%, P < .001) and more patients as lower risk (63.8% v 54.2%, P < .001) than did RS among 1,444 N0 ER-positive patients. In B-20, the interaction of RSPC with chemotherapy was not statistically significant (P = .10), in contrast to the previously reported significant interaction of RS with chemotherapy (P = .037).

Conclusion: RSPC refines the assessment of distant recurrence risk and reduces the number of patients classified as intermediate risk. Adding clinicopathologic measures did not seem to enhance the value of RS alone nor the individual biology RS identifies in predicting chemotherapy benefit.

A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients.
Laurel A Habel, Steven Shak, +12 authors, Charles P Quesenberry.
Breast Cancer Res, 2006 Jun 02; 8(3). PMID: 16737553    Free PMC article.
Highly Cited.
Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer.
P M Ravdin, L A Siminoff, +4 authors, H L Parker.
J Clin Oncol, 2001 Feb 22; 19(4). PMID: 11181660
Highly Cited.
Flexible parametric proportional-hazards and proportional-odds models for censored survival data, with application to prognostic modelling and estimation of treatment effects.
Patrick Royston, Mahesh K B Parmar.
Stat Med, 2002 Sep 05; 21(15). PMID: 12210632
Highly Cited.
A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors.
B Fisher, J Costantino, +7 authors, E R Fisher.
N Engl J Med, 1989 Feb 23; 320(8). PMID: 2644532
Highly Cited.
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 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.
Comparison of the prognostic and predictive utilities of the 21-gene Recurrence Score assay and Adjuvant! for women with node-negative, ER-positive breast cancer: results from NSABP B-14 and NSABP B-20.
Gong Tang, Steven Shak, +6 authors, Norman Wolmark.
Breast Cancer Res Treat, 2011 Jan 12; 127(1). PMID: 21221771    Free PMC article.
Random-effects model for meta-analysis of clinical trials: an update.
Rebecca DerSimonian, Raghu Kacker.
Contemp Clin Trials, 2006 Jun 30; 28(2). PMID: 16807131
Highly Cited.
American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer.
Lyndsay Harris, Herbert Fritsche, +7 authors, American Society of Clinical Oncology.
J Clin Oncol, 2007 Oct 24; 25(33). PMID: 17954709
Highly Cited. Review.
Evaluating the predictiveness of a continuous marker.
Ying Huang, Margaret Sullivan Pepe, Ziding Feng.
Biometrics, 2007 May 11; 63(4). PMID: 17489968    Free PMC article.
Prognostic utility of the 21-gene assay in hormone receptor-positive operable breast cancer compared with classical clinicopathologic features.
Lori J Goldstein, Robert Gray, +12 authors, Joseph A Sparano.
J Clin Oncol, 2008 Aug 06; 26(25). PMID: 18678838    Free PMC article.
Highly Cited.
Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial.
Kathy S Albain, William E Barlow, +20 authors, Breast Cancer Intergroup of North America.
Lancet Oncol, 2009 Dec 17; 11(1). PMID: 20005174    Free PMC article.
Highly Cited.
Prediction of risk of distant recurrence using the 21-gene recurrence score in node-negative and node-positive postmenopausal patients with breast cancer treated with anastrozole or tamoxifen: a TransATAC study.
Mitch Dowsett, Jack Cuzick, +11 authors, Steven Shak.
J Clin Oncol, 2010 Mar 10; 28(11). PMID: 20212256
Highly Cited.
Toward individualized breast cancer therapy: translating biological concepts to the bedside.
Gabriel N Hortobagyi.
Oncologist, 2012 Apr 05; 17(4). PMID: 22474069    Free PMC article.
Why does Oncotype DX recurrence score reduce adjuvant chemotherapy use?
Jeffrey G Schneider, Danny N Khalil.
Breast Cancer Res Treat, 2012 Jun 23; 134(3). PMID: 22723033    Free PMC article.
High-risk estrogen-receptor-positive breast cancer: identification and implications for therapy.
Rosemary L Balleine, Nicholas R Wilcken.
Mol Diagn Ther, 2012 Jul 21; 16(4). PMID: 22812573
Review.
Integrating comparative effectiveness design elements and endpoints into a phase III, randomized clinical trial (SWOG S1007) evaluating oncotypeDX-guided management for women with breast cancer involving lymph nodes.
Scott D Ramsey, William E Barlow, +6 authors, Gabriel N Hortobagyi.
Contemp Clin Trials, 2012 Sep 25; 34(1). PMID: 23000081    Free PMC article.
Review.
The 21-gene recurrence score assay impacts adjuvant therapy recommendations for ER-positive, node-negative and node-positive early breast cancer resulting in a risk-adapted change in chemotherapy use.
W Eiermann, M Rezai, +13 authors, J Blohmer.
Ann Oncol, 2012 Nov 09; 24(3). PMID: 23136233    Free PMC article.
Utility of prognostic genomic tests in breast cancer practice: The IMPAKT 2012 Working Group Consensus Statement.
H A Azim, S Michiels, +9 authors, C Swanton.
Ann Oncol, 2013 Jan 23; 24(3). PMID: 23337633    Free PMC article.
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.
Has discovery-based cancer research been a bust?
R J Epstein.
Clin Transl Oncol, 2013 Sep 05; 15(11). PMID: 24002944
Proliferation and estrogen signaling can distinguish patients at risk for early versus late relapse among estrogen receptor positive breast cancers.
Giampaolo Bianchini, Lajos Pusztai, +16 authors, Luca Gianni.
Breast Cancer Res, 2013 Sep 26; 15(5). PMID: 24060333    Free PMC article.
Genomic instability: a stronger prognostic marker than proliferation for early stage luminal breast carcinomas.
Anne Vincent-Salomon, Vanessa Benhamo, +13 authors, Olivier Delattre.
PLoS One, 2013 Oct 22; 8(10). PMID: 24143191    Free PMC article.
The impact of the Oncotype DX Recurrence Score on treatment decisions and clinical outcomes in patients with early breast cancer: the Maccabi Healthcare Services experience with a unified testing policy.
Nava Siegelmann-Danieli, Barbara Silverman, +3 authors, Avi Porath.
Ecancermedicalscience, 2014 Jan 05; 7. PMID: 24386009    Free PMC article.
[Determination of proliferation in breast cancer by immunohistochemical detection of Ki-67].
M Christgen, W Winkens, H H Kreipe.
Pathologe, 2014 Jan 15; 35(1). PMID: 24414612
Genomic profiling in luminal breast cancer.
Oleg Gluz, Daniel Hofmann, +3 authors, Nadia Harbeck.
Breast Care (Basel), 2014 Feb 20; 8(6). PMID: 24550749    Free PMC article.
Review.
Cost-effectiveness analysis of prognostic gene expression signature-based stratification of early breast cancer patients.
Patricia R Blank, Martin Filipits, +11 authors, Michael Gnant.
Pharmacoeconomics, 2014 Nov 19; 33(2). PMID: 25404424    Free PMC article.
The 21-gene recurrence score complements IBTR! Estimates in early-stage, hormone receptor-positive, HER2-normal, lymph node-negative breast cancer.
Nikhil G Thaker, Karen E Hoffman, +10 authors, Wendy A Woodward.
Springerplus, 2015 Feb 13; 4. PMID: 25674496    Free PMC article.
[Molecular pathology for breast cancer: Importance of the gene expression profile].
C Denkert, B M Pfitzner, B I Heppner, M Dietel.
Pathologe, 2015 Apr 04; 36(2). PMID: 25836324
Review.
Breast cancer subtype intertumor heterogeneity: MRI-based features predict results of a genomic assay.
Elizabeth J Sutton, Jung Hun Oh, +5 authors, Elizabeth A Morris.
J Magn Reson Imaging, 2015 Apr 09; 42(5). PMID: 25850931    Free PMC article.
Highly Cited.
A Validated Model for Identifying Patients Unlikely to Benefit From the 21-Gene Recurrence Score Assay.
Michele M Gage, Martin Rosman, +6 authors, Lorraine Tafra.
Clin Breast Cancer, 2015 Jun 15; 15(6). PMID: 26072275    Free PMC article.
Adoption of Gene Expression Profiling for Breast Cancer in US Oncology Practice for Women Younger Than 65 Years.
Suzanne C O'Neill, Claudine Isaacs, +8 authors, Arnold L Potosky.
J Natl Compr Canc Netw, 2015 Oct 21; 13(10). PMID: 26483061    Free PMC article.
Patient-specific meta-analysis for risk assessment using multivariate proportional hazards regression.
Michael R Crager, Gong Tang.
J Appl Stat, 2014 Jan 01; 41(12). PMID: 26664111    Free PMC article.
Recommendations from the EGAPP Working Group: does the use of Oncotype DX tumor gene expression profiling to guide treatment decisions improve outcomes in patients with breast cancer?
Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group*.
Genet Med, 2015 Dec 19; 18(8). PMID: 26681310
Low Concordance between Gene Expression Signatures in ER Positive HER2 Negative Breast Carcinoma Could Impair Their Clinical Application.
Enora Laas, Peter Mallon, +3 authors, Fabien Reyal.
PLoS One, 2016 Feb 20; 11(2). PMID: 26895349    Free PMC article.
Prognostic Impact of 21-Gene Recurrence Score in Patients With Stage IV Breast Cancer: TBCRC 013.
Tari A King, Jaclyn P Lyman, +17 authors, Clifford A Hudis.
J Clin Oncol, 2016 Mar 24; 34(20). PMID: 27001590    Free PMC article.
The Role of the 21-Gene Recurrence Score in Breast Cancer Treatment.
Josee-Lyne Ethier, Eitan Amir.
Mol Diagn Ther, 2016 May 29; 20(4). PMID: 27235162
Review.
Association between Ultrasound Features and the 21-Gene Recurrence Score Assays in Patients with Oestrogen Receptor-Positive, HER2-Negative, Invasive Breast Cancer.
Eun Young Chae, Woo Kyung Moon, +8 authors, Sei Hyun Ahn.
PLoS One, 2016 Jul 01; 11(6). PMID: 27362843    Free PMC article.
Comparison of EndoPredict and EPclin With Oncotype DX Recurrence Score for Prediction of Risk of Distant Recurrence After Endocrine Therapy.
Richard Buus, Ivana Sestak, +7 authors, Mitch Dowsett.
J Natl Cancer Inst, 2016 Jul 13; 108(11). PMID: 27400969    Free PMC article.
Highly Cited.
Retrospective analysis of molecular scores for the prediction of distant recurrence according to baseline risk factors.
Ivana Sestak, Mitch Dowsett, +2 authors, Jack Cuzick.
Breast Cancer Res Treat, 2016 Jul 23; 159(1). PMID: 27447876    Free PMC article.
Synchronous invasive ductal carcinoma in encapsulated papillary ductal carcinoma.
J P Regan, J T Casaubon, E Genelus-Dominique.
J Surg Case Rep, 2016 Aug 27; 2016(8). PMID: 27562577    Free PMC article.
Distribution patterns of 21-gene recurrence score in 980 Chinese estrogen receptor-positive, HER2-negative early breast cancer patients.
Jiayi Wu, Yan Fang, +11 authors, Kunwei Shen.
Oncotarget, 2017 Apr 14; 8(24). PMID: 28404972    Free PMC article.
Comparison of Oncotype DX® Recurrence Score® with other risk assessment tools including the Nottingham Prognostic Index in the identification of patients with low-risk invasive breast cancer.
Maura Bríd Cotter, Alex Dakin, +5 authors, Cecily M Quinn.
Virchows Arch, 2017 Jul 15; 471(3). PMID: 28707056
Internet tools to enhance breast cancer care.
Shlomit Strulov Shachar, Hyman B Muss.
NPJ Breast Cancer, 2016 Apr 27; 2. PMID: 28721377    Free PMC article.
Adjusting for covariates in evaluating markers for selecting treatment, with application to guiding chemotherapy for treating estrogen-receptor-positive, node-positive breast cancer.
Holly Janes, Marshall D Brown, +2 authors, William E Barlow.
Contemp Clin Trials, 2017 Aug 19; 63. PMID: 28818434    Free PMC article.
Comparison of risk classification between EndoPredict and MammaPrint in ER-positive/HER2-negative primary invasive breast cancer.
Alberto Peláez-García, Laura Yébenes, +9 authors, David Hardisson.
PLoS One, 2017 Sep 09; 12(9). PMID: 28886093    Free PMC article.
Discordance between oncotype DX recurrence score and RSPC for predicting residual risk of recurrence in ER-positive breast cancer.
Andrew Dodson, David Okonji, +6 authors, Mitch Dowsett.
Breast Cancer Res Treat, 2017 Nov 13; 168(1). PMID: 29128896    Free PMC article.
Can Interrogation of Tumour Characteristics Lead us to Safely Omit Adjuvant Radiotherapy in Patients with Early Breast Cancer?
I S Bhattacharya, A M Kirby, J M Bliss, C E Coles.
Clin Oncol (R Coll Radiol), 2018 Jan 15; 30(3). PMID: 29331262    Free PMC article.
Review.
Comparison of the Performance of 6 Prognostic Signatures for Estrogen Receptor-Positive Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial.
Ivana Sestak, Richard Buus, +9 authors, Mitch Dowsett.
JAMA Oncol, 2018 Feb 17; 4(4). PMID: 29450494    Free PMC article.
Highly Cited.
Spotlight on the utility of the Oncotype DX® breast cancer assay.
Zhen Rong Siow, Richard H De Boer, Geoffrey J Lindeman, G Bruce Mann.
Int J Womens Health, 2018 Mar 06; 10. PMID: 29503586    Free PMC article.
Review.
Combined pathologic-genomic algorithm for early-stage breast cancer improves cost-effective use of the 21-gene recurrence score assay.
M M Gage, W C Mylander, +9 authors, R S Jackson.
Ann Oncol, 2018 May 23; 29(5). PMID: 29788166    Free PMC article.
A nomogram to predict adjuvant chemotherapy recommendation in breast cancer patients with intermediate recurrence score.
Feilin Qu, Xiaosong Chen, +10 authors, Kunwei Shen.
Chin J Cancer Res, 2018 Jun 05; 30(2). PMID: 29861607    Free PMC article.
Development and validation of a new predictive model for breast cancer survival in New Zealand and comparison to the Nottingham prognostic index.
J Mark Elwood, Essa Tawfiq, +5 authors, Ross Lawrenson.
BMC Cancer, 2018 Sep 19; 18(1). PMID: 30223800    Free PMC article.
Evaluation of the Incorporation of Recurrence Score into the American Joint Committee on Cancer Eighth Edition Staging System in Patients with T1-2N0M0, Estrogen Receptor-Positive, Human Epidermal Growth Receptor 2-Negative Invasive Breast Cancer: A Population-Based Analysis.
Shuning Ding, Jiayi Wu, +6 authors, Li Zhu.
Oncologist, 2019 Apr 26; 24(11). PMID: 31019021    Free PMC article.
Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer.
Joseph A Sparano, Robert J Gray, +27 authors, George W Sledge.
N Engl J Med, 2019 Jun 04; 380(25). PMID: 31157962    Free PMC article.
Highly Cited.
Clinical validation of an immunohistochemistry-based CanAssist-Breast test for distant recurrence prediction in hormone receptor-positive breast cancer patients.
Manjiri M Bakre, Charusheila Ramkumar, +10 authors, Mark D Pegram.
Cancer Med, 2019 Mar 09; 8(4). PMID: 30848103    Free PMC article.
The impact of Oncotype DX breast cancer assay results on clinical practice: a UK experience.
Valerie E Crolley, Husam Marashi, +12 authors, Judy King.
Breast Cancer Res Treat, 2020 Mar 15; 180(3). PMID: 32170635    Free PMC article.
Simulation Modeling to Extend Clinical Trials of Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Early Breast Cancer.
Jinani Jayasekera, Joseph A Sparano, +5 authors, Jeanne Mandelblatt.
JNCI Cancer Spectr, 2020 Apr 28; 3(4). PMID: 32337487    Free PMC article.
The 21-Gene Recurrence Score Assay and Prediction of Chemotherapy Benefit: A Propensity Score-Matched Analysis of the SEER Database.
In Sil Choi, Jiwoong Jung, +5 authors, Ki-Tae Hwang.
Cancers (Basel), 2020 Jul 12; 12(7). PMID: 32650374    Free PMC article.
Prognosis vs Treatment Interaction.
Jack Cuzick.
JNCI Cancer Spectr, 2018 Apr 28; 2(1). PMID: 31360838    Free PMC article.
A Novel Prognostic Scoring System Integrating Gene Expressions and Clinicopathological Characteristics to Predict Very Early Relapse in Node-Negative Estrogen Receptor-Positive/HER2-Negative Breast Cancer.
Caijin Lin, Jiayi Wu, +8 authors, Li Zhu.
Front Oncol, 2020 Oct 13; 10. PMID: 33042787    Free PMC article.