Breast Cancer Research and Treatment

, Volume 163, Issue 2, pp 303–310 | Cite as

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. RobertsEmail author
  • Dave P. Miller
  • Steven Shak
  • Valentina I. Petkov



The Oncotype DX® Breast Recurrence Score™ (RS) assay is validated to predict breast cancer (BC) recurrence and adjuvant chemotherapy benefit in select patients with lymph node-positive (LN+), hormone receptor-positive (HR+), HER2-negative BC. We assessed 5-year BC-specific survival (BCSS) in LN+ patients with RS results in SEER databases.


In this population-based study, BC cases in SEER registries (diagnosed 2004–2013) were linked to RS results from assays performed by Genomic Health (2004–2014). The primary analysis included only patients (diagnosed 2004–2012) with LN+ (including micrometastases), HR+ (per SEER), and HER2-negative (per RT-PCR) primary invasive BC (N = 6768). BCSS, assessed by RS category and number of positive lymph nodes, was calculated using the actuarial method.


The proportion of patients with RS results and LN+ disease (N = 8782) increased over time between 2004 and 2013, and decreased with increasing lymph node involvement from micrometastases to ≥4 lymph nodes. Five-year BCSS outcomes for those with RS < 18 ranged from 98.9% (95% CI 97.4–99.6) for those with micrometastases to 92.8% (95% CI 73.4–98.2) for those with ≥4 lymph nodes. Similar patterns were found for patients with RS 18–30 and RS ≥ 31. RS group was strongly predictive of BCSS among patients with micrometastases or up to three positive lymph nodes (p < 0.001).


Overall, 5-year BCSS is excellent for patients with RS < 18 and micrometastases, one or two positive lymph nodes, and worsens with additionally involved lymph nodes. Further analyses should account for treatment variables, and longitudinal updates will be important to better characterize utilization of Oncotype DX testing and long-term survival outcomes.


Breast cancer Disease-specific survival Lymph node-positive Oncotype DX Recurrence Score SEER 



One positive lymph node


One to three positive lymph nodes


Two positive lymph nodes


Two to three positive lymph nodes


Three positive lymph nodes


Four or more positive lymph nodes


Analysis of variance


Breast cancer


Breast cancer-specific survival


Confidence interval


Estrogen receptor


Human epidermal growth factor receptor 2


Hormone receptor-positive (ER-positive, PR-positive, or both)


Lymph node-positive




Progesterone receptor


Recurrence Score®


Reverse transcription-polymerase chain reaction


Treatment (Rx) for positive node, endocrine-responsive breast cancer


Standard deviation


Surveillance, epidemiology, and end results


Socioeconomic status



We acknowledge Anna Lau for medical writing and editorial assistance. The ideas and opinions expressed herein are those of the author(s) and endorsement by any State, Department of Public Health, the National Cancer Institute, the Centers for Disease Control and Prevention, or their Contractors and Subcontractors is not intended nor should be inferred. The Surveillance, Epidemiology and End Results (SEER) Program is funded by the National Cancer Institute (NCI). Genomic Health performed the work to electronically submit the Recurrence Score results, but provided no funding for this study. We acknowledge the SEER registries for collecting the SEER data.

Compliance with ethical standards

Conflict of interest

Dr. Roberts and Dr. Petkov declare no conflicts of interest. Mr. Dave Miller and Dr. Stephen Shak are employed by and have stock ownership in Genomic Health Inc.

Supplementary material

10549_2017_4162_MOESM1_ESM.pdf (364 kb)
Supplementary material 1 (PDF 364 kb)


  1. 1.
    Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, Baehner FL, Walker MG, Watson D, Park T, Hiller W, Fisher ER, Wickerham DL, Bryant J, Wolmark N (2004) A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 351(27):2817–2826. doi: 10.1056/NEJMoa041588 CrossRefPubMedGoogle Scholar
  2. 2.
    Paik S, Tang G, Shak S, Kim C, Baker J, Kim W, Cronin M, Baehner FL, Watson D, Bryant J, Costantino JP, Geyer CE Jr, Wickerham DL, Wolmark N (2006) Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol 24(23):3726–3734. doi: 10.1200/JCO.2005.04.7985 CrossRefPubMedGoogle Scholar
  3. 3.
    Albanell J, Gonzalez A, Ruiz-Borrego M, Alba E, Garcia-Saenz JA, Corominas JM, Burgues O, Furio V, Rojo A, Palacios J, Bermejo B, Martinez-Garcia M, Limon ML, Munoz AS, Martin M, Tusquets I, Rojo F, Colomer R, Faull I, Lluch A (2012) Prospective transGEICAM study of the impact of the 21-gene Recurrence Score assay and traditional clinicopathological factors on adjuvant clinical decision making in women with estrogen receptor-positive (ER+) node-negative breast cancer. Ann Oncol 23(3):625–631. doi: 10.1093/annonc/mdr278 CrossRefPubMedGoogle Scholar
  4. 4.
    Asad J, Jacobson AF, Estabrook A, Smith SR, Boolbol SK, Feldman SM, Osborne MP, Boachie-Adjei K, Twardzik W, Tartter PI (2008) Does Oncotype DX Recurrence Score affect the management of patients with early-stage breast cancer? Am J Surg 196(4):527–529. doi: 10.1016/j.amjsurg.2008.06.021 CrossRefPubMedGoogle Scholar
  5. 5.
    Henry LR, Stojadinovic A, Swain SM, Prindiville S, Cordes R, Soballe PW (2009) The influence of a gene expression profile on breast cancer decisions. J Surg Oncol 99(6):319–323. doi: 10.1002/jso.21244 CrossRefPubMedGoogle Scholar
  6. 6.
    Joh JE, Esposito NN, Kiluk JV, Laronga C, Lee MC, Loftus L, Soliman H, Boughey JC, Reynolds C, Lawton TJ, Acs PI, Gordan L, Acs G (2011) The effect of Oncotype DX Recurrence Score on treatment recommendations for patients with estrogen receptor-positive early stage breast cancer and correlation with estimation of recurrence risk by breast cancer specialists. Oncologist 16(11):1520–1526. doi: 10.1634/theoncologist.2011-0045 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Dinan MA, Mi X, Reed SD, Lyman GH, Curtis LH (2015) Association between use of the 21-gene Recurrence Score assay and receipt of chemotherapy among medicare beneficiaries with early-stage breast cancer, 2005–2009. JAMA Oncol 1(8):1098–1109. doi: 10.1001/jamaoncol.2015.2722 CrossRefPubMedGoogle Scholar
  8. 8.
    Reed SD, Dinan MA, Schulman KA, Lyman GH (2013) Cost-effectiveness of the 21-gene recurrence score assay in the context of multifactorial decision making to guide chemotherapy for early-stage breast cancer. Genet Med 15(3):203–211. doi: 10.1038/gim.2012.119 CrossRefPubMedGoogle Scholar
  9. 9.
    Trosman JR, Van Bebber SL, Phillips KA (2010) Coverage policy development for personalized medicine: private payer perspectives on developing policy for the 21-gene assay. J Oncol Pract 6(5):238–242. doi: 10.1200/JOP.000075 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Albain KS, Barlow WE, Shak S, Hortobagyi GN, Livingston RB, Yeh IT, Ravdin P, Bugarini R, Baehner FL, Davidson NE, Sledge GW, Winer EP, Hudis C, Ingle JN, Perez EA, Pritchard KI, Shepherd L, Gralow JR, Yoshizawa C, Allred DC, Osborne CK, Hayes DF, Breast Cancer Intergroup of North America (2010) 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. Lancet Oncol 11(1):55–65. doi: 10.1016/S1470-2045(09)70314-6 CrossRefPubMedGoogle Scholar
  11. 11.
    Dowsett M, Cuzick J, Wale C, Forbes J, Mallon EA, Salter J, Quinn E, Dunbier A, Baum M, Buzdar A, Howell A, Bugarini R, Baehner FL, Shak S (2010) 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. J Clin Oncol 28(11):1829–1834. doi: 10.1200/JCO.2009.24.4798 CrossRefPubMedGoogle Scholar
  12. 12.
    National Comprehensive Cancer Network (2015) NCCN Clinical practice guidelines in oncology: breast cancer. Invasive breast cancer.
  13. 13.
    Wong WB, Ramsey SD, Barlow WE, Garrison LP Jr, Veenstra DL (2012) The value of comparative effectiveness research: projected return on investment of the RxPONDER trial (SWOG S1007). Contemp Clin Trials 33(6):1117–1123. doi: 10.1016/j.cct.2012.08.006 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Grenader T, Yerushalmi R, Tokar M, Fried G, Kaufman B, Peretz T, Geffen DB (2014) The 21-gene recurrence score assay (Oncotype DX) in estrogen receptor-positive male breast cancer: experience in an Israeli cohort. Oncology 87(1):1–6. doi: 10.1159/000360793 CrossRefPubMedGoogle Scholar
  15. 15.
    National Center for Health Statistics (2016) Accessed 6 July 2016
  16. 16.
    Howlader N, Ries LA, Mariotto AB, Reichman ME, Ruhl J, Cronin KA (2010) Improved estimates of cancer-specific survival rates from population-based data. J Natl Cancer Inst 102(20):1584–1598. doi: 10.1093/jnci/djq366 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Noone AM, Lund JL, Mariotto A, Cronin K, McNeel T, Deapen D, Warren JL (2016) Comparison of SEER treatment data with medicare claims. Med Care 54(9):e55–e64. doi: 10.1097/MLR.0000000000000073 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Petkov V, Miller DP, Howlader N, Gliner N, Howe W, Schussler N, Cronin K, Baehner FL, Cress R, Deapen D, Glaser SL, Hernandez BY, Lynch CF, Mueller L, Schwartz AG, Schwartz SM, Stroup A, Sweeney C, Tucker TC, Ward KC, Wiggins C, Wu X, Penberthy L, Shak S (2016) Breast-cancer-specific mortality in patients treated based on the 21-gene assay: a SEER population-based study. NPJ Breast Cancer 2:16017. doi: 10.1038/npjbcancer.2016.17 CrossRefGoogle Scholar
  19. 19.
    Roberts MC, Weinberger M, Dusetzina SB, Dinan MA, Reeder-Hayes KE, Carey LA, Troester MA, Wheeler SB (2016) Racial variation in the uptake of oncotype DX testing for early-stage breast cancer. J Clin Oncol 34(2):130–138. doi: 10.1200/JCO.2015.63.2489 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York (outside the USA) 2017

Authors and Affiliations

  • Megan C. Roberts
    • 1
    Email author
  • Dave P. Miller
    • 2
  • Steven Shak
    • 2
  • Valentina I. Petkov
    • 1
  1. 1.National Cancer InstituteBethesdaUSA
  2. 2.Genomic Health Inc.Redwood CityUSA

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