Tumor Biology

, Volume 35, Issue 4, pp 3113–3117 | Cite as

Two-gene expression ratio as predictor for breast cancer treated with tamoxifen: evidence from meta-analysis

  • Lin Zhao
  • Shimiao Zhu
  • Ying Gao
  • Yaogang Wang
Research Article


A HOXB13-to-IL17BR expression ratio was previously identified to predict a clinical outcome of breast cancer patients treated with adjuvant tamoxifen. A large number of studies were addressed to confirm its function as a predictor of breast cancer outcome treated with tamoxifen. However, conflicting results were got. In this study, a systematic search of databases was carried out, and other relevant papers were also identified. Then, the analyses were conducted according to the PRISMA and MOOSE guidelines. After full review, 11 studies with a total of 2,958 participants were deemed eligible and were included in the study. Pooled results revealed that women with higher HOXB13-to-IL17BR expression ratio had significantly worse outcomes in breast patients treated with tamoxifen, especially for those who are negative of node.


HOXB13 IL17BR Meta-analysis Breast cancer Tamoxifen 



The work was supported by the Key Project of Science and Technology, Tianjin Municipal Science and Technology Commission (grant no. 11ZCGYSY02200). The authors thank all of the authors of primary studies included in their meta-analyses.

Conflicts of interest



  1. 1.
    Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365:1687–717.CrossRefGoogle Scholar
  2. 2.
    Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351:2817–26.PubMedCrossRefGoogle Scholar
  3. 3.
    Ma XJ, Wang Z, Ryan PD, Isakoff SJ, Barmettler A, Fuller A, et al. A two-gene expression ratio predicts clinical outcome in breast cancer patients treated with tamoxifen. Cancer Cell. 2004;5:607–16.PubMedCrossRefGoogle Scholar
  4. 4.
    Fan C, Oh DS, Wessels L, Weigelt B, Nuyten DS, Nobel AB, et al. Concordance among gene-expression-based predictors for breast cancer. N Engl J Med. 2006;355:560–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Wang Y, Klijn JG, Zhang Y, Sieuwerts AM, Look MP, Yang F, et al. Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet. 2005;365:671–9.PubMedCrossRefGoogle Scholar
  6. 6.
    van’t Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415:530–6.CrossRefGoogle Scholar
  7. 7.
    Goetz MP, Suman VJ, Ingle JN, Nibbe AM, Visscher DW, Reynolds CA, et al. A two-gene expression ratio of homeobox 13 and interleukin-17b receptor for prediction of recurrence and survival in women receiving adjuvant tamoxifen. Clin Cancer Res. 2006;12:2080–7.PubMedCrossRefGoogle Scholar
  8. 8.
    Sgroi DC, Carney E, Zarrella E, Steffel L, Binns SN, Finkelstein DM, et al. Prediction of late disease recurrence and extended adjuvant letrozole benefit by the HOBX13/IL17BR biomarker. J Natl Cancer Inst. 2013;105:1036–42.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Ma XJ, Hilsenbeck SG, Wang W, Ding L, Sgroi DC, Bender RA, et al. The HOBX13:IL17BR expression index is a prognostic factor in early-stage breast cancer. J Clin Oncol. 2006;24:4611–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Kok M, Linn SC, Van Laar RK, Jansen MP, van den Berg TM, Delahaye LJ, et al. Comparison of gene expression profiles predicting progression in breast cancer patients treated with tamoxifen. Breast Cancer Res Treat. 2009;113:275–83.PubMedCrossRefGoogle Scholar
  11. 11.
    Jerevall PL, Brommesson S, Strand C, Gruvberger-Saal S, Malmstrom P, Nordenskjold B, et al. Exploring the two-gene ratio in breast cancer-independent roles for HOBX13 and IL17BR in prediction of clinical outcome. Breast Cancer Res Treat. 2008;107:225–34.PubMedCrossRefGoogle Scholar
  12. 12.
    Habel LA, Sakoda LC, Achacoso N, Ma XJ, Erlander MG, Sgroi DC, et al. HOBX13: IL17BR and molecular grade index and risk of breast cancer death among patients with lymph node-negative invasive disease. Breast Cancer Res. 2013;15:R24.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Reid JF, Lusa L, De Cecco L, Coradini D, Veneroni S, Daidone MG, et al. Limits of predictive models using microarray data for breast cancer clinical treatment outcome. J Natl Cancer Inst. 2005;97:927–30.PubMedCrossRefGoogle Scholar
  14. 14.
    Jansen MP, Sieuwerts AM, Look MP, Ritstier K, Meijer-van GM, van Staveren IL, et al. HOBX13-to-IL17BR expression ratio is related with tumor aggressiveness and response to tamoxifen of recurrent breast cancer: a retrospective study. J Clin Oncol. 2007;25:662–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Zhu S, Zhang H, Xie L, Chen J, Niu Y. Risk factors and prevention of inguinal hernia after radical prostatectomy: a systematic review and meta-analysis. J Urol. 2013;189:884–90.PubMedCrossRefGoogle Scholar
  16. 16.
    Zhang H, Zhu S, Chen J, Tang Y, Hu H, Mohan V, et al. Peroxisome proliferator-activated receptor γ polymorphism Pro12Ala is associated with nephropathy in type 2 diabetes: evidence from meta-analysis of 18 studies. Diabetes Care. 2012;35:1388–93.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Ewing CM, Ray AM, Lange EM, Zuhlke KA, Robbins CM, Tembe WD, et al. Germline mutations in HOXB13 and prostate-cancer risk. N Engl J Med. 2012;366:141–9.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Shang Z, Zhu S, Zhang H, Li L, Niu Y. Germline homeobox b13 (HOXB13) G84E mutation and prostate cancer risk in European descendants: a meta-analysis of 24,213 cases and 73,631 controls. Eur Urol. 2013;64:173–6.PubMedCrossRefGoogle Scholar
  19. 19.
    Okuda H, Toyota M, Ishida W, Furihata M, Tsuchiya M, Kamada M, et al. Epigenetic inactivation of the candidate tumor suppressor gene HOXB13 in human renal cell carcinoma. Oncogene. 2006;25:1733–42.PubMedCrossRefGoogle Scholar
  20. 20.
    Shah N, Jin K, Cruz LA, Park S, Sadik H, Cho S, et al. HOXB13 mediates tamoxifen resistance and invasiveness in human breast cancer by suppressing ERalpha and inducing IL-6 expression. Cancer Res. 2013;73:5449–58.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  1. 1.International Medical SchoolTianjin Medical UniversityTianjinChina
  2. 2.Department of Urology, The Tianjin Institute of UrologyThe Second Hospital of Tianjin Medical UniversityTianjinChina
  3. 3.School of Public HealthTianjin Medical UniversityTianjinChina

Personalised recommendations