This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jansen, M. P.H.M. Articles by Berns, E. M.J.J. Search for Related Content PubMed PubMed Citation Articles by Jansen, M. P.H.M. Articles by Berns, E. M.J.J.

HOXB13-to-IL17BR Expression Ratio Is Related With Tumor Aggressiveness and Response to Tamoxifen of Recurrent Breast Cancer: A Retrospective Study

Maurice P.H.M. Jansen, Anieta M. Sieuwerts, Maxime P. Look, Kirsten Ritstier, Marion E. Meijer-van Gelder, Iris L. van Staveren, Jan G.M. Klijn, John A. Foekens, Els M.J.J. Berns

From the Department of Medical Oncology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam, the Netherlands

Address reprint requests to Maurice P.H.M. Jansen, PhD, Erasmus MC, Department of Medical Oncology, Josephine Nefkens Institute, PO Box 2040, 3000 CA Rotterdam, the Netherlands; e-mail: m.p.h.m.jansen{at}erasmusmc.nl

PURPOSE: A HOXB13-to-IL17BR expression ratio was previously identified to predict clinical outcome of breast cancer patients treated with adjuvant tamoxifen. However, this ratio may predict a tumor's response to tamoxifen, its intrinsic aggressiveness, or both.

PATIENTS AND METHODS: We have measured the HOXB13 and IL17BR expression levels by real-time polymerase chain reaction in 1,252 primary breast tumor specimens. Expression levels were normalized to housekeeper gene levels and related to clinicopathologic factors for all patients. The primary objective of this study was to determine the relationship of a HOXB13-to-IL17BR ratio with tumor aggressiveness and/or with response to tamoxifen therapy in estrogen receptor (ER) -positive disease. We selected ER-positive tumors, and clinical end points for the HOXB13-to-IL17BR ratio were disease-free survival (DFS) in patients with primary breast cancer (N = 619) and progression-free survival (PFS) in patients with recurrent breast cancer treated with first-line tamoxifen monotherapy (N = 193). The odds ratio (OR) and hazard ratio (HR) and their 95% CI were calculated, and all P values were two-sided.

RESULTS: The HOXB13-to-IL17BR ratio was significantly associated with DFS and PFS. In multivariate analysis, HOXB13-to-IL17BR ratio expression levels were associated with a shorter DFS for node-negative patients only. Corrected for traditional predictive factors, the dichotomized HOXB13-to-IL17BR ratio was the strongest predictor in multivariate analysis for a poor response to tamoxifen therapy (OR = 0.16; 95% CI, 0.06 to 0.45; P < .001) and a shorter PFS (HR = 2.97; 95% CI, 1.82 to 4.86; P < .001).

CONCLUSION: High HOXB13-to-IL17BR ratio expression levels associate with both tumor aggressiveness and tamoxifen therapy failure.

Supported by Grant No. DDHK 2001-2364 of the Dutch Cancer Society, Amsterdam, the Netherlands, and in part by the Netherlands Genomics Initiative/ Netherlands Organization for Scientific Research.

Presented in part at the Fifth European Breast Cancer Conference, Nice, France, March 21-25, 2006. Both M.P.H.M.J. and A.M.S. contributed equally to this article.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

This article has been cited by other articles:

				B. A.T. Rodriguez, A. S.L. Cheng, P. S. Yan, D. Potter, F. J. Agosto-Perez, C. L. Shapiro, and T. H.-M. Huang Epigenetic repression of the estrogen-regulated Homeobox B13 gene in breast cancer Carcinogenesis, July 1, 2008; 29(7): 1459 - 1465. [Abstract] [Full Text] [PDF]

				X.-J. Ma, R. Salunga, S. Dahiya, W. Wang, E. Carney, V. Durbecq, A. Harris, P. Goss, C. Sotiriou, M. Erlander, et al. A Five-Gene Molecular Grade Index and HOXB13:IL17BR Are Complementary Prognostic Factors in Early Stage Breast Cancer Clin. Cancer Res., May 1, 2008; 14(9): 2601 - 2608. [Abstract] [Full Text] [PDF]

				L. Marchionni, R. F. Wilson, A. C. Wolff, S. Marinopoulos, G. Parmigiani, E. B. Bass, and S. N. Goodman Systematic Review: Gene Expression Profiling Assays in Early-Stage Breast Cancer Ann Intern Med, March 4, 2008; 148(5): 358 - 369. [Abstract] [Full Text] [PDF]

				D. Meijer, A. M Sieuwerts, M. P Look, T. van Agthoven, J. A Foekens, and L. C J Dorssers Fibroblast growth factor receptor 4 predicts failure on tamoxifen therapy in patients with recurrent breast cancer Endocr. Relat. Cancer, March 1, 2008; 15(1): 101 - 111. [Abstract] [Full Text] [PDF]

				L. Harris, H. Fritsche, R. Mennel, L. Norton, P. Ravdin, S. Taube, M. R. Somerfield, D. F. Hayes, and R. C. Bast Jr American Society of Clinical Oncology 2007 Update of Recommendations for the Use of Tumor Markers in Breast Cancer J. Clin. Oncol., November 20, 2007; 25(33): 5287 - 5312. [Abstract] [Full Text] [PDF]

				Z. Wang, S. Dahiya, H. Provencher, B. Muir, E. Carney, K. Coser, T. Shioda, X.-J. Ma, and D. C. Sgroi The Prognostic Biomarkers HOXB13, IL17BR, and CHDH Are Regulated by Estrogen in Breast Cancer Clin. Cancer Res., November 1, 2007; 13(21): 6327 - 6334. [Abstract] [Full Text] [PDF]