Journal Article
. 2013 Jul;31(22).
doi: 10.1200/JCO.2012.46.1558.

Comparison of PAM50 risk of recurrence score with oncotype DX and IHC4 for predicting risk of distant recurrence after endocrine therapy

Mitch Dowsett 1 Ivana Sestak  Elena Lopez-Knowles  Kalvinder Sidhu  Anita K Dunbier  J Wayne Cowens  Sean Ferree  James Storhoff  Carl Schaper  Jack Cuzick  
Affiliations
  • PMID: 23816962
  •     190 citations

Abstract

Purpose: Risk of distant recurrence (DR) among women with estrogen receptor (ER) -positive early breast cancer is the major determinant of recommendations for or against chemotherapy. It is frequently estimated using the Oncotype DX recurrence score (RS). The PAM50 risk of recurrence (ROR) score provides an alternative approach, which also identifies intrinsic subtypes.

Patients And Methods: mRNA from 1,017 patients with ER-positive primary breast cancer treated with anastrozole or tamoxifen in the ATAC trial was assessed for ROR using the NanoString nCounter. Likelihood ratio (LR) tests and concordance indices (c indices) were used to assess the prognostic information provided beyond that of a clinical treatment score (CTS) by RS, ROR, or IHC4, an index of DR risk derived from immunohistochemical assessment of ER, progesterone receptor, human epidermal growth factor receptor 2 (HER2), and Ki67.

Results: ROR added significant prognostic information beyond CTS in all patients (Δ LR-χ(2) = 33.9; P < .001) and in all four subgroups: node negative, node positive, HER2 negative, and HER2 negative/node negative; more information was added by ROR than by RS. C indices in the HER2-negative/node-negative subgroup were 0.73, 0.76, and 0.78 for CTS, CTS plus RS, and CTS plus ROR, respectively. More patients were scored as high risk and fewer as intermediate risk by ROR than by RS. Relatively similar prognostic information was added by ROR and IHC4 in all patients but more by ROR in the HER2-negative/node-negative group.

Conclusion: ROR provides more prognostic information in endocrine-treated patients with ER-positive, node-negative disease than RS, with better differentiation of intermediate- and higher-risk groups.

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Prospective, multicenter French study evaluating the clinical impact of the Breast Cancer Intrinsic Subtype-Prosigna® Test in the management of early-stage breast cancers.
Delphine Hequet, Céline Callens, +20 authors, Roman Rouzier.
PLoS One, 2017 Oct 19; 12(10). PMID: 29045452    Free PMC article.
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M C Chang, L H Souter, +6 authors, Molecular Oncology Advisory Committee.
Curr Oncol, 2017 Nov 02; 24(5). PMID: 29089811    Free PMC article.
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Hege O Ohnstad, Elin Borgen, +11 authors, Bjørn Naume.
Breast Cancer Res, 2017 Nov 16; 19(1). PMID: 29137653    Free PMC article.
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Breast Cancer Res Treat, 2017 Nov 28; 168(1). PMID: 29177605    Free PMC article.
Biomarkers in breast cancer: A consensus statement by the Spanish Society of Medical Oncology and the Spanish Society of Pathology.
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Clin Transl Oncol, 2017 Dec 24; 20(7). PMID: 29273958    Free PMC article.
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Can Interrogation of Tumour Characteristics Lead us to Safely Omit Adjuvant Radiotherapy in Patients with Early Breast Cancer?
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Clin Oncol (R Coll Radiol), 2018 Jan 15; 30(3). PMID: 29331262    Free PMC article.
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Molecular Signatures of Radiation Response in Breast Cancer: Towards Personalized Decision-Making in Radiation Treatment.
Corey Speers, Lori J Pierce.
Int J Breast Cancer, 2018 Jan 20; 2017. PMID: 29348942    Free PMC article.
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Can Histological Grade and Mitotic Index Replace Ki67 to Determine Luminal Breast Cancer Subtypes?
David Oddó, Dahiana Pulgar, +11 authors, César Sánchez.
Asian Pac J Cancer Prev, 2018 Jan 28; 19(1). PMID: 29373911    Free PMC article.
A study of association of Oncotype DX recurrence score with DCE-MRI characteristics using multivariate machine learning models.
Ashirbani Saha, Michael R Harowicz, Weiyao Wang, Maciej A Mazurowski.
J Cancer Res Clin Oncol, 2018 Feb 11; 144(5). PMID: 29427210    Free PMC article.
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.
Luminal A Breast Cancer and Molecular Assays: A Review.
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Oncologist, 2018 Feb 24; 23(5). PMID: 29472313    Free PMC article.
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Indian J Med Res, 2018 Mar 08; 146(5). PMID: 29512598    Free PMC article.
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Investigating a multigene prognostic assay based on significant pathways for Luminal A breast cancer through gene expression profile analysis.
Haiyan Gao, Mei Yang, Xiaolan Zhang.
Oncol Lett, 2018 Mar 17; 15(4). PMID: 29545900    Free PMC article.
Stanniocalcin Expression as a Predictor of Late Breast Cancer Recurrence.
Kristen D Brantley, Anders Kjærsgaard, +5 authors, Timothy L Lash.
Cancer Epidemiol Biomarkers Prev, 2018 Mar 30; 27(6). PMID: 29593009    Free PMC article.
De-escalation of breast radiotherapy after conserving surgery in low-risk early breast cancer patients.
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Med Oncol, 2018 Apr 05; 35(5). PMID: 29616366
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Integration of Clinical Variables for the Prediction of Late Distant Recurrence in Patients With Estrogen Receptor-Positive Breast Cancer Treated With 5 Years of Endocrine Therapy: CTS5.
Mitch Dowsett, Ivana Sestak, +5 authors, Jack Cuzick.
J Clin Oncol, 2018 Apr 21; 36(19). PMID: 29676944    Free PMC article.
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South Asian J Cancer, 2018 May 04; 7(2). PMID: 29721472    Free PMC article.
Combined pathologic-genomic algorithm for early-stage breast cancer improves cost-effective use of the 21-gene recurrence score assay.
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Ann Oncol, 2018 May 23; 29(5). PMID: 29788166    Free PMC article.
Precision Medicine for Breast Cancer: The Paths to Truly Individualized Diagnosis and Treatment.
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Int J Breast Cancer, 2018 Jun 05; 2018. PMID: 29862084    Free PMC article.
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The Dilemma of HER2 Double-equivocal Breast Carcinomas: Genomic Profiling and Implications for Treatment.
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Am J Surg Pathol, 2018 Jul 06; 42(9). PMID: 29975246    Free PMC article.
Gene expression assay and Watson for Oncology for optimization of treatment in ER-positive, HER2-negative breast cancer.
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PLoS One, 2018 Jul 07; 13(7). PMID: 29979736    Free PMC article.
Using Probability for Pathological Complete Response (pCR) as a Decision Support Marker for Neoadjuvant Chemotherapy in HER2 Negative Breast Cancer Patients - a Survey Among Physicians.
Paul Gass, Michael Untch, +18 authors, Naiba Nabieva.
Geburtshilfe Frauenheilkd, 2018 Jul 31; 78(7). PMID: 30057427    Free PMC article.
Enzyme-free digital counting of endogenous circular RNA molecules in B-cell malignancies.
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Lab Invest, 2018 Aug 09; 98(12). PMID: 30087459    Free PMC article.
Genomic Testing in the Management of Early-Stage Breast Cancer.
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J Clin Outcomes Manag, 2017 May 01; 24(5). PMID: 30158821    Free PMC article.
Novel 18-gene signature for predicting relapse in ER-positive, HER2-negative breast cancer.
Richard Buus, Belinda Yeo, +7 authors, Mitch Dowsett.
Breast Cancer Res, 2018 Sep 06; 20(1). PMID: 30180877    Free PMC article.
Predictive markers of endocrine response in breast cancer.
Duniya Mosly, Arran Turnbull, +2 authors, Simon Langdon.
World J Exp Med, 2018 Sep 08; 8(1). PMID: 30191138    Free PMC article.
An Update on Breast Cancer Multigene Prognostic Tests-Emergent Clinical Biomarkers.
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Front Med (Lausanne), 2018 Sep 21; 5. PMID: 30234119    Free PMC article.
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Highly Cited. Review.
An assessment of prognostic immunity markers in breast cancer.
Benlong Yang, Jeff Chou, +13 authors, Zhiyuan Hu.
NPJ Breast Cancer, 2018 Nov 06; 4. PMID: 30393759    Free PMC article.
Update Breast Cancer 2018 (Part 3) - Genomics, Individualized Medicine and Immune Therapies - in the Middle of a New Era: Prevention and Treatment Strategies for Early Breast Cancer.
Achim Wöckel, Michael P Lux, +17 authors, Hans-Christian Kolberg.
Geburtshilfe Frauenheilkd, 2018 Dec 01; 78(11). PMID: 30498278    Free PMC article.
Panoptic View of Prognostic Models for Personalized Breast Cancer Management.
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Multigene expression signatures in early hormone receptor positive HER 2 negative breast cancer.
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Radiol Oncol, 2019 Sep 26; 53(3). PMID: 31553709    Free PMC article.
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Role of miR-10b-5p in the prognosis of breast cancer.
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PeerJ, 2019 Oct 04; 7. PMID: 31579605    Free PMC article.
Incidence of Late Relapses in Patients With HER2-Positive Breast Cancer Receiving Adjuvant Trastuzumab: Combined Analysis of NCCTG N9831 (Alliance) and NRG Oncology/NSABP B-31.
Saranya Chumsri, Zhuo Li, +9 authors, E Aubrey Thompson.
J Clin Oncol, 2019 Oct 18; 37(35). PMID: 31622131    Free PMC article.
Deciphering HER2 Breast Cancer Disease: Biological and Clinical Implications.
Ana Godoy-Ortiz, Alfonso Sanchez-Muñoz, +4 authors, Emilio Alba.
Front Oncol, 2019 Nov 19; 9. PMID: 31737566    Free PMC article.
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An independent poor-prognosis subtype of breast cancer defined by a distinct tumor immune microenvironment.
Xavier Tekpli, Tonje Lien, +17 authors, Vessela N Kristensen.
Nat Commun, 2019 Dec 05; 10(1). PMID: 31796750    Free PMC article.
Detection of disseminated tumor cells in bone marrow predict late recurrences in operable breast cancer patients.
Kjersti Tjensvoll, Oddmund Nordgård, +3 authors, Bjørnar Gilje.
BMC Cancer, 2019 Nov 23; 19(1). PMID: 31752747    Free PMC article.
Decision of Adjuvant Systemic Treatment in HR+ HER2- Early Invasive Breast Cancer: Which Biomarkers Could Help?
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Cancer Manag Res, 2019 Dec 19; 11. PMID: 31849525    Free PMC article.
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Evaluation of the 12-Gene Molecular Score and the 21-Gene Recurrence Score as Predictors of Response to Neo-adjuvant Chemotherapy in Estrogen Receptor-Positive, HER2-Negative Breast Cancer.
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Ann Surg Oncol, 2020 Jan 08; 27(3). PMID: 31907749    Free PMC article.
Omission of postoperative radiation after breast conserving surgery: A progressive paradigm shift towards precision medicine.
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Sci Rep, 2019 Aug 23; 9(1). PMID: 31434940    Free PMC article.
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Breast cancer PAM50 signature: correlation and concordance between RNA-Seq and digital multiplexed gene expression technologies in a triple negative breast cancer series.
A C Picornell, I Echavarria, +17 authors, M Martin.
BMC Genomics, 2019 Jun 05; 20(1). PMID: 31159741    Free PMC article.
A Multigene Assay Determines Risk of Recurrence in Patients with Triple-Negative Breast Cancer.
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Cancer Res, 2019 May 03; 79(13). PMID: 31048497    Free PMC article.
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Rolf Søkilde, Helena Persson, +11 authors, Carlos Rovira.
BMC Genomics, 2019 Jun 19; 20(1). PMID: 31208318    Free PMC article.
Validation of CTS5 model in large-scale breast cancer population and the impact of menopausal and HER2 status on its prognostic value.
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Sci Rep, 2020 Mar 15; 10(1). PMID: 32170181    Free PMC article.
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Ontario Health (Quality).
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Absolute Improvements in Freedom From Distant Recurrence to Tailor Adjuvant Endocrine Therapies for Premenopausal Women: Results From TEXT and SOFT.
Olivia Pagani, Prudence A Francis, +13 authors, SOFT and TEXT Investigators and International Breast Cancer Study Group.
J Clin Oncol, 2019 Oct 17; 38(12). PMID: 31618131    Free PMC article.
MiR-891a-5p as a prognostic marker and therapeutic target for hormone receptor-positive breast cancer.
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J Cancer, 2020 Apr 25; 11(13). PMID: 32328182    Free PMC article.
Independent Validation of EarlyR Gene Signature in BIG 1-98: A Randomized, Double-Blind, Phase III Trial Comparing Letrozole and Tamoxifen as Adjuvant Endocrine Therapy for Postmenopausal Women With Hormone Receptor-Positive, Early Breast Cancer.
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JNCI Cancer Spectr, 2020 Apr 28; 3(4). PMID: 32337480    Free PMC article.
Programmed death-ligand 1 gene expression is a prognostic marker in early breast cancer and provides additional prognostic value to 21-gene and 70-gene signatures in estrogen receptor-positive disease.
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Mol Oncol, 2020 Mar 03; 14(5). PMID: 32115850    Free PMC article.
Commercially Available Gene Expression Assays as Predictive Tools for Adjuvant Radiotherapy? A Critical Review.
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Case 22-2020: A 62-Year-Old Woman with Early Breast Cancer during the Covid-19 Pandemic.
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N Engl J Med, 2020 Jul 02; 383(3). PMID: 32610007    Free PMC article.
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J Natl Cancer Inst, 2019 Nov 20; 112(7). PMID: 31742342    Free PMC article.
Chemotherapy benefit for 'ER-positive' breast cancer and contamination of nonluminal subtypes—waiting for TAILORx and RxPONDER.
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Do YOU know the Ki-67 index of your breast cancer patients? Knowledge of your institution's Ki-67 index distribution and its robustness is essential for decision-making in early breast cancer.
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Profiling of Invasive Breast Carcinoma Circulating Tumour Cells-Are We Ready for the 'Liquid' Revolution?
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Automated Quantification of Extranuclear ERα using Phosphor-integrated Dots for Predicting Endocrine Therapy Resistance in HR+/HER2- Breast Cancer.
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Tumor location of the central and nipple portion is associated with impaired survival for women with breast cancer.
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Should a Multigene Signature be Used in all Luminal Early Breast Cancers.
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LobSig is a multigene predictor of outcome in invasive lobular carcinoma.
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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.
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Discordance of the PAM50 Intrinsic Subtypes Compared with Immunohistochemistry-Based Surrogate in Breast Cancer Patients: Potential Implication of Genomic Alterations of Discordance.
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Re-interpretation of PAM50 gene expression as quantitative tumor dimensions shows utility for clinical trials: application to prognosis and response to paclitaxel in breast cancer.
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Development of a Prognostic Tool to Guide the Decision to Extend Adjuvant Aromatase Inhibitors for up to Ten Years in Postmenopausal Early Breast Cancer Patients.
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