Research article

Redefining prognostic factors for breast cancer: YB-1 is a stronger predictor of relapse and disease-specific survival than estrogen receptor or HER-2 across all tumor subtypes

Golareh Habibi¹ , Samuel Leung² , Jennifer H Law¹ , Karen Gelmon³ , Hamid Masoudi⁴ , Dmitry Turbin² , Michael Pollak⁵ , Torsten O Nielsen² , David Huntsman^2,4 and Sandra E Dunn¹

¹  Laboratory for Oncogenomic Research, Departments of Pediatrics and Experimental Medicine, Child and Family Research Institute, W. 28th Avenue, University of British Columbia, Vancouver, BC, V5Z 4H4, Canada

²  Genetic Pathology Evaluation Center, Jack Bell Research Center, Oak Street, Vancouver, BC, V6H 3Z6, Canada

³  Division of Medical Oncology, British Columbia Cancer Agency, West 10th Avenue, Vancouver, BC, V5Z 1L3 Canada

⁴  Department of Pathology and Laboratory, West 10th Avenue, Vancouver, BC, V5Z 1L3, Canada

⁵  Division of Medical Oncology, Jewish General Hospital – Lady Davis Institute, Côte Ste Catherine Road, Montreal, Quebec H3T 1E2, Canada

author email corresponding author email

Breast Cancer Research 2008, 10:R86doi:10.1186/bcr2156

Published:	16 October 2008

Abstract

Introduction

Gene expression analysis is used to subtype breast cancers such that the most aggressive tumors are identified, but translating this into clinical practice can be cumbersome. Our goal is to develop a universal biomarker that distinguishes patients at high risk across all breast cancer subtypes. We previously reported that Y-box binding protein-1 (YB-1), a transcription/translation factor, was a marker of poor prognosis in a cohort of 490 patients with breast cancer, but the study was not large enough to subtype the cancers. We therefore investigated whether YB-1 identifies patients at risk for either reduced relapse free survival or decreased r breast cancer specific survival (BCSS) across all tumor subtypes by evaluating 4,049 cases.

Methods

Tumor tissue microarrays, representing 4,049 cases of invasive breast cancers with 20 years of follow up, were subtyped by the expression profiles of estrogen receptor, progesterone receptor, or HER-2. We then addressed whether YB-1 expression identified patients at higher risk for relapse and/or lower BCSS.

Results

We found YB-1 to be a highly predictive biomarker of relapse (P < 2.5 × 10^-20) and poor survival (P < 7.3 × 10^-26) in the entire cohort and across all breast cancer subtypes. Patients with node-positive or node-negative cancer were more likely to die from the disease if YB-1 was expressed. This was further substantiated using a Cox regression model, which revealed that it was significantly associated with relapse and poor survival in a subtype independent manner (relapse patients, hazard ratio = 1.28, P < 8 × 10^-3; all patients, hazard ratio = 1.45, P < 6.7 × 10^-7). Moreover, YB-1 was superior to estrogen receptor and HER-2 as a prognostic marker for relapse and survival. For a subset of patients who were originally considered low risk and were therefore not given chemotherapy, YB-1 was indicative of poor survival (P < 7.1 × 10 ^-17). Likewise, YB-1 was predictive of decreased BCSS in tamoxifen-treated patients (P = 0.001); in this setting a Cox regression model once again demonstrated it to be an independent biomarker indicating poor survival (hazard ratio = 1.70, P = 0.022).

Conclusions

Expression of YB-1 universally identifies patients at high risk across all breast cancer subtypes and in situations where more aggressive treatment may be needed. We therefore propose that YB-1 may re-define high-risk breast cancer and thereby create opportunities for individualized therapy.