Journal of Clinical Oncology, Vol 25, No 6 (February 20), 2007: pp. 662-668
© 2007 American Society of Clinical Oncology.
DOI: 10.1200/JCO.2006.07.3676
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.

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