Abstract 4413: A 5-gene model predicts clinical outcome in ER+/PR+, early stage breast cancers treated with adjuvant tamoxifen
Authors: Daniel Alan Kerr, James L. Wittliff
Journal: Cancer Research (2011)

Abstract Purpose: Patients with primary breast carcinomas expressing of both estrogen (ERα) and progesterone receptors (PR) are more likely to respond to Tamoxifen therapy than those with ERα and PR negative cancers, especially in women with early stage lesions. However, a significant number of these patients exhibiting clinicopathologic features suggesting good response and prognosis will relapse within 10 years. Additional markers are needed to identify patients at risk for breast cancer recurrence after administrative hormone therapy. Procedures: Ten candidate genes associated with estrogen signaling were selected from a group of 200 genes identified from microarray studies of laser capture microdissected breast carcinoma cells of ER positive breast cancers and combined with those for conventional biomarkers (ESR1, PGR, ERBB2). Carcinoma cell content and pathology of each biopsy was confirmed. Expression of this 13-gene subset was analyzed by RT-qPCR in de-identified frozen tissue specimens from early stage, ER+/PR+ breast cancers treated with adjuvant Tamoxifen. A multivariate model was created by Cox regression using a training set of tissue sections from 36 biopsy specimens, and then applied to an independent validation set of sections from 24 specimens. Results: A 5-gene model was derived from the training set that exhibited significant correlations with both relapse-free and overall survival. Applying this model to Kaplan-Meier regression, patients were separated into low risk (100% relapse-free at 150 months) and high risk (60% relapse-free at 150 months) groups (P = 0.03). When this model was applied to the validation set, similar risk stratification was achieved for both relapse-free and overall survival (P = 0.01 and 0.04, respectively). No significant difference in clinical features (e.g., tumor grade, tumor size and nodal status) was observed between the high and low risk groups. Conclusions: We developed a 5-gene model composed of PgR, BCL2, ERBB4 JM-a, RERG and CD34 that identified a subset of early stage, ER+/PR+ breast cancers patients treated with Tamoxifen that exhibited high recurrence rates, although their clinicopathologic features suggested good prognosis and response. Furthermore, absence of association of the 5-gene model with tumor grade suggests the gene expression profile provides clinically relevant predictive information independent of proliferation. Supported in part by grants from the Phi Beta Psi Sorority Charity Trust and a CTSP award from the Commonwealth of Kentucky. DAK was a recipient of a Graduate Fellowship from the Integrated Programs in Biomedical Sciences, University of Louisville, and the Spatola Graduate Fellowship from IMD3. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4413. doi:10.1158/1538-7445.AM2011-4413