Review
. 2018 Aug;4().
doi: 10.1038/s41523-018-0082-6.

Clinical relevance of the 21-gene Recurrence Score® assay in treatment decisions for patients with node-positive breast cancer in the genomic era

Eleftherios P Mamounas 1 Christy A Russell 2 Anna Lau 2 Michelle P Turner 2 Kathy S Albain 3 
Affiliations
  • PMID: 30155517
  •     28 References
  •     6 citations

Abstract

In contemporary management of early-stage breast cancer, clinical decisions regarding adjuvant systemic therapy are increasingly made after considering both genomic assay results and clinico-pathologic features. Genomic information augments the prognostic information gleaned from clinico-pathologic features by providing risk estimates for distant recurrence and/or breast cancer-specific survival based on individual tumor biology. The 21-gene Oncotype DX Breast Recurrence Score® (RS) assay is validated to be prognostic and predictive of chemotherapy benefit in patients with hormone receptor-positive (HR+), HER2-negative early-stage breast cancer, regardless of nodal status. Because patients frequently are recommended to receive adjuvant chemotherapy based on the perceived poor prognosis related to a positive nodal status, inconsistent use of any prognostic genomic assay in the node-positive (N+) setting likely results in overtreatment of some patients, particularly those with a low genomic risk as defined by the RS test. This comprehensive review of the evidence for the RS assay in patients with N+, HR+, HER2-negative early-stage breast cancer focuses on outcomes of patients with low RS results treated with hormonal therapy alone. Aggregate findings show that the RS assay consistently identifies patients with low genomic risk N+ breast cancer, in whom adjuvant chemotherapy can be avoided without adversely affecting outcomes. This evidence suggests that HR+ patients with limited nodal involvement and low RS results should discuss with their physicians the pros and cons of adjuvant chemotherapy at the time their treatment plans are being decided.

Analytical validation of the Oncotype DX genomic diagnostic test for recurrence prognosis and therapeutic response prediction in node-negative, estrogen receptor-positive breast cancer.
Maureen Cronin, Chithra Sangli, +7 authors, Drew Watson.
Clin Chem, 2007 Apr 28; 53(6). PMID: 17463177
Highly Cited.
Biology of breast cancer in young women.
Hatem A Azim, Ann H Partridge.
Breast Cancer Res, 2014 Dec 02; 16(4). PMID: 25436920    Free PMC article.
Highly Cited. Review.
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.
Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial.
M Baum, A U Budzar, +5 authors, ATAC Trialists' Group.
Lancet, 2002 Jul 02; 359(9324). PMID: 12090977
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.
De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017.
G Curigliano, H J Burstein, +52 authors, B Xu.
Ann Oncol, 2017 Aug 26; 28(8). PMID: 28838210    Free PMC article.
Highly Cited.
Tumor-related prognostic factors for breast cancer.
W L Donegan.
CA Cancer J Clin, 1997 Jan 01; 47(1). PMID: 8996077
Review.
Breast-cancer-specific mortality in patients treated based on the 21-gene assay: a SEER population-based study.
Valentina I Petkov, Dave P Miller, +21 authors, Steven Shak.
NPJ Breast Cancer, 2017 Jul 20; 2. PMID: 28721379    Free PMC article.
Highly Cited.
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.
Use of archived specimens in evaluation of prognostic and predictive biomarkers.
Richard M Simon, Soonmyung Paik, Daniel F Hayes.
J Natl Cancer Inst, 2009 Oct 10; 101(21). PMID: 19815849    Free PMC article.
Highly Cited.
Adjuvant chemotherapy and timing of tamoxifen in postmenopausal patients with endocrine-responsive, node-positive breast cancer: a phase 3, open-label, randomised controlled trial.
Kathy S Albain, William E Barlow, +18 authors, Breast Cancer Intergroup of North America.
Lancet, 2009 Dec 17; 374(9707). PMID: 20004966    Free PMC article.
Clinical outcomes in ER+ HER2 -node-positive breast cancer patients who were treated according to the Recurrence Score results: evidence from a large prospectively designed registry.
Salomon M Stemmer, Mariana Steiner, +13 authors, Noa Ben-Baruch.
NPJ Breast Cancer, 2017 Sep 14; 3. PMID: 28900632    Free PMC article.
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
Prognostic factors versus predictive factors: Examples from a clinical trial of erlotinib.
Gary M Clark.
Mol Oncol, 2009 Apr 23; 1(4). PMID: 19383314    Free PMC article.
Biomarker: Predictive or Prognostic?
Karla V Ballman.
J Clin Oncol, 2015 Sep 24; 33(33). PMID: 26392104
Highly Cited. Review.
Prognostic factors in breast cancer: current and new predictors of metastasis.
D F Hayes, C Isaacs, V Stearns.
J Mammary Gland Biol Neoplasia, 2002 May 16; 6(4). PMID: 12013528
Review.
Reducing chemotherapy use in clinically high-risk, genomically low-risk pN0 and pN1 early breast cancer patients: five-year data from the prospective, randomised phase 3 West German Study Group (WSG) PlanB trial.
Ulrike Nitz, Oleg Gluz, +18 authors, Nadia Harbeck.
Breast Cancer Res Treat, 2017 Jul 01; 165(3). PMID: 28664507    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.
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.
Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.
E Senkus, S Kyriakides, +6 authors, ESMO Guidelines Committee.
Ann Oncol, 2015 Sep 01; 26 Suppl 5. PMID: 26314782
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.
West German Study Group Phase III PlanB Trial: First Prospective Outcome Data for the 21-Gene Recurrence Score Assay and Concordance of Prognostic Markers by Central and Local Pathology Assessment.
Oleg Gluz, Ulrike A Nitz, +18 authors, Nadia Harbeck.
J Clin Oncol, 2016 Mar 02; 34(20). PMID: 26926676
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.
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.
The HER-2/neu oncogene in breast cancer: prognostic factor, predictive factor, and target for therapy.
J S Ross, J A Fletcher.
Stem Cells, 1998 Dec 01; 16(6). PMID: 9831867
Highly Cited. Review.
Improved disease-free survival with epirubicin-based chemoendocrine adjuvant therapy compared with tamoxifen alone in one to three node-positive, estrogen-receptor-positive, postmenopausal breast cancer patients: results of French Adjuvant Study Group 02 and 07 trials.
M Namer, P Fargeot, +8 authors, French Adjuvant Study Group.
Ann Oncol, 2005 Dec 20; 17(1). PMID: 16361531
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.
National Institutes of Health Consensus Development Conference Statement: adjuvant therapy for breast cancer, November 1-3, 2000.
P Eifel, J A Axelson, +11 authors, D Roter.
J Natl Cancer Inst, 2001 Jul 05; 93(13). PMID: 11438563
Highly Cited. Review.
Impact of adjuvant chemotherapy on the survival of patients with breast cancer diagnosed by screening.
Irene Zarcos-Pedrinaci, Maximino Redondo, +12 authors, REDISSEC-CaMISS Group.
Cancer Med, 2019 Sep 25; 8(15). PMID: 31549794    Free PMC article.
Multigene expression signatures in early hormone receptor positive HER 2 negative breast cancer.
Tanja Ovcaricek, Iztok Takac, Erika Matos.
Radiol Oncol, 2019 Sep 26; 53(3). PMID: 31553709    Free PMC article.
Review.
Impact of deviation from guideline recommended treatment on breast cancer survival in Asia.
Peh Joo Ho, Samuel Guan Wei Ow, +12 authors, Mikael Hartman.
Sci Rep, 2020 Jan 30; 10(1). PMID: 31992769    Free PMC article.
A Radiation Oncologist's Guide to Axillary Management in Breast Cancer: A Walk Through the Trials.
Julie K Jang, Elana R Sverdlik, Naomi R Schechter.
Curr Breast Cancer Rep, 2020 Mar 28; 11(4). PMID: 32215182    Free PMC article.
Racial and ethnic disparities in 21-gene recurrence scores, chemotherapy, and survival among women with hormone receptor-positive, node-negative breast cancer.
Yunan Han, Zhi-Feng Miao, +3 authors, Ying Liu.
Breast Cancer Res Treat, 2020 Sep 16; 184(3). PMID: 32929567    Free PMC article.
Development and Validation of a Preoperative Magnetic Resonance Imaging Radiomics-Based Signature to Predict Axillary Lymph Node Metastasis and Disease-Free Survival in Patients With Early-Stage Breast Cancer.
Yunfang Yu, Yujie Tan, +23 authors, Herui Yao.
JAMA Netw Open, 2020 Dec 09; 3(12). PMID: 33289845    Free PMC article.