Journal Article
. 2019 Nov;7(18).
doi: 10.21037/atm.2019.08.82.

Impact of the 21-gene recurrence score assay on chemotherapy decision making and outcomes for breast cancer patients with four or more positive lymph nodes

Qing-Hong Zhang 1 Wen-Wen Zhang 2 Jun Wang 3 Chen-Lu Lian 3 Jia-Yuan Sun 2 Zhen-Yu He 2 San-Gang Wu 3 
  • PMID: 31700882
  •     25 References


Background: To assess the impact of the 21-gene recurrence score (RS) on chemotherapy decision making and survival outcomes for breast cancer patients with >4 positive lymph nodes.

Methods: Patients with non-metastatic estrogen receptor-positive breast cancer with >4 positive lymph nodes diagnosed between 2004 and 2013 were identified using the Surveillance, Epidemiology, and End Results database. The relationships between the 21-gene RS value and survival outcomes, chemotherapy decision-making, and chemotherapy benefit were analyzed.

Results: A total of 410 patients were identified, including 191 (46.6%), 164 (40.0%), and 55 (13.4%) in the low-, intermediate-, and high-risk RS groups, respectively. The 21-gene RS assay results were independently related to chemotherapy receipt. A total of 59.0%, 68.0%, and 78.0% of patients received chemotherapy in the low-, intermediate-, and high-risk RS groups, respectively. The 21-gene RS was an independent indicator of breast cancer specific survival (BCSS) and overall survival (OS). Intermediate-risk [BCSS: hazards ratio (HR), 2.832, 95% confidence interval (CI): 1.160-6.910, P=0.022; OS: HR, 3.704, 95% CI: 1.750-7.836, P=0.001] and high-risk RS (BCSS: HR, 6.440, 95% CI: 2.597-15.974, P<0.001; OS: HR, 5.053, 95% CI: 2.199-11.608, P<0.001) cohorts had significantly lower survival outcomes compared to low-risk RS cohort. The 5-year BCSS were 92.7%, 88.3%, and 70.7% in patients in the low-, intermediate-, and high-risk RS cohorts, respectively (P<0.001), and the 5-year OS were 92.1%, 80.6%, and 66.6%, respectively (P<0.001).

Conclusions: The 21-gene RS is an independent predictor of chemotherapy receipt and survival outcomes for breast cancer patients with > 4 positive lymph nodes.

Keywords: Breast neoplasms; Oncotype; clinical decision-making; lymph node; survival.

Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials.
Early Breast Cancer Trialists' Collaborative Group (EBCTCG), R Peto, +15 authors, K Pritchard.
Lancet, 2011 Dec 14; 379(9814). PMID: 22152853    Free PMC article.
Highly Cited.
The Prognostic Significance of the Oncotype DX Recurrence Score in T1-2N1M0 Estrogen Receptor-Positive HER2-Negative Breast Cancer Based on the Prognostic Stage in the Updated AJCC 8th Edition.
Maoli Wang, Kejin Wu, +3 authors, Hongliang Chen.
Ann Surg Oncol, 2018 Nov 21; 26(5). PMID: 30456680
Prospective Evaluation of the Impact of the 21-Gene Recurrence Score Assay on Adjuvant Treatment Decisions for Women with Node-Positive Breast Cancer in Ontario, Canada.
Sofia Torres, Maureen Trudeau, +7 authors, Andrea Eisen.
Oncologist, 2018 Jan 27; 23(7). PMID: 29371476    Free PMC article.
The Distribution and Outcomes of the 21-Gene Recurrence Score in T1-T2N0 Estrogen Receptor-Positive Breast Cancer With Different Histologic Subtypes.
Jun Wang, Zhen-Yu He, +3 authors, San-Gang Wu.
Front Genet, 2019 Jan 09; 9. PMID: 30619463    Free PMC article.
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.
Routine Use of Oncotype DX Recurrence Score Testing in Node-Positive Hormone Receptor-Positive HER2-Negative Breast Cancer: The Time Has Come.
Elizabeth A Mittendorf, Tari A King.
Ann Surg Oncol, 2019 Feb 25; 26(5). PMID: 30798446
Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials.
Early Breast Cancer Trialists' Collaborative Group (EBCTCG).
Lancet, 2005 May 17; 365(9472). PMID: 15894097
Highly Cited.
Comparison of SEER Treatment Data With Medicare Claims.
Anne-Michelle Noone, Jennifer L Lund, +4 authors, Joan L Warren.
Med Care, 2014 Mar 19; 54(9). PMID: 24638121    Free PMC article.
Highly Cited.
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.
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.
Long-term toxic effects of adjuvant chemotherapy in breast cancer.
H A Azim, E de Azambuja, +2 authors, M J Piccart.
Ann Oncol, 2011 Feb 04; 22(9). PMID: 21289366
Primary Therapy of Early Breast Cancer: Evidence, Controversies, Consensus: Spectrum of Opinion of German Specialists on the 16th St. Gallen International Breast Cancer Conference (Vienna 2019).
Michael Untch, Christoph Thomssen, +21 authors, Nadia Harbeck.
Geburtshilfe Frauenheilkd, 2019 Jun 21; 79(6). PMID: 31217628    Free PMC article.
21-Gene Recurrence Score for prognosis and prediction of taxane benefit after adjuvant chemotherapy plus endocrine therapy: results from NSABP B-28/NRG Oncology.
Eleftherios P Mamounas, Gong Tang, +14 authors, Norman Wolmark.
Breast Cancer Res Treat, 2017 Nov 13; 168(1). PMID: 29128898    Free PMC article.
The value of comparative effectiveness research: projected return on investment of the RxPONDER trial (SWOG S1007).
William B Wong, Scott D Ramsey, +2 authors, David L Veenstra.
Contemp Clin Trials, 2012 Sep 18; 33(6). PMID: 22981891    Free PMC article.
The impact of the 21-gene Recurrence Score assay on clinical decision-making in node-positive (up to 3 positive nodes) estrogen receptor-positive breast cancer patients.
Salomon M Stemmer, Shmuel H Klang, +7 authors, Nicky Lieberman.
Breast Cancer Res Treat, 2013 Jun 27; 140(1). PMID: 23801158    Free PMC article.
New and Important Changes in the TNM Staging System for Breast Cancer.
Gabriel N Hortobagyi, Stephen B Edge, Armando Giuliano.
Am Soc Clin Oncol Educ Book, 2018 Sep 21; 38. PMID: 30231399
The effects of lymph node status on predicting outcome in ER+ /HER2- tamoxifen treated breast cancer patients using gene signatures.
Jessica G Cockburn, Robin M Hallett, +5 authors, Anita Bane.
BMC Cancer, 2016 Jul 30; 16. PMID: 27469239    Free PMC article.
The 21-gene Recurrence Score® assay predicts distant recurrence in lymph node-positive, hormone receptor-positive, breast cancer patients treated with adjuvant sequential epirubicin- and docetaxel-based or epirubicin-based chemotherapy (PACS-01 trial).
Frédérique Penault-Llorca, Thomas Filleron, +12 authors, Henri Roché.
BMC Cancer, 2018 May 08; 18(1). PMID: 29728098    Free PMC article.
Utilization and impact of 21-gene recurrence score assay for breast cancer in clinical practice across the United States: lessons learned from the 2010 to 2012 National Cancer Data Base analysis.
Amila Orucevic, Robert E Heidel, John L Bell.
Breast Cancer Res Treat, 2016 May 22; 157(3). PMID: 27206678    Free PMC article.
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 Focused Update.
Ian Krop, Nofisat Ismaila, +10 authors, Vered Stearns.
J Clin Oncol, 2017 Jul 12; 35(24). PMID: 28692382    Free PMC article.
Highly Cited.
Lymph Node Status in Breast Cancer Does Not Predict Tumor Biology.
Danielle M Bello, Christy Russell, +2 authors, Monica Morrow.
Ann Surg Oncol, 2018 Jul 04; 25(10). PMID: 29968028    Free PMC article.
Impact of Genomic Assay Testing and Clinical Factors on Chemotherapy Use After Implementation of Standardized Testing Criteria.
Kelsey H Natsuhara, Katya Losk, +7 authors, Rachel A Freedman.
Oncologist, 2018 Aug 05; 24(5). PMID: 30076279    Free PMC article.
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.
Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†.
F Cardoso, S Kyriakides, +6 authors, ESMO Guidelines Committee. Electronic address:
Ann Oncol, 2019 Jun 05; 30(8). PMID: 31161190
Highly Cited.
Breast cancer-specific survival in patients with lymph node-positive hormone receptor-positive invasive breast cancer and Oncotype DX Recurrence Score results in the SEER database.
Megan C Roberts, Dave P Miller, Steven Shak, Valentina I Petkov.
Breast Cancer Res Treat, 2017 Mar 01; 163(2). PMID: 28243896