Clinical Cancer Research CTRC-AACR San Antonio Breast Cancer Symposium Translational Cancer Medicine 2008: Cancer Clinical Trials and Personalized Medicine
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Clinical Cancer Research Vol. 11, 8623-8631, December 15, 2005
© 2005 American Association for Cancer Research


Imaging, Diagnosis, Prognosis

Tumor Gene Expression and Prognosis in Breast Cancer Patients with 10 or More Positive Lymph Nodes

Melody A. Cobleigh1, Bita Tabesh1, Pincas Bitterman1, Joffre Baker2, Maureen Cronin2, Mei-Lan Liu2, Russell Borchik1, Juan-Miguel Mosquera1, Michael G. Walker2 and Steven Shak2

Authors' Affiliations: 1 Rush University Medical Center, Chicago, Illinois and 2 Genomic Health, Inc., Redwood City, California

Requests for reprints: Melody A. Cobleigh, Rush University Medical Center, Professional Building, 1725 West Harrison, Suite 821, Chicago, IL 60612. Phone: 312-942-2242; Fax: 312-563-3123; E-mail: melody_cobleigh{at}rush.edu.

Purpose: This study, along with two others, was done to develop the 21-gene Recurrence Score assay (Oncotype DX) that was validated in a subsequent independent study and is used to aid decision making about chemotherapy in estrogen receptor (ER)–positive, node-negative breast cancer patients.

Experimental Design: Patients with ≥10 nodes diagnosed from 1979 to 1999 were identified. RNA was extracted from paraffin blocks, and expression of 203 candidate genes was quantified using reverse transcription-PCR (RT-PCR).

Results: Seventy-eight patients were studied. As of August 2002, 77% of patients had distant recurrence or breast cancer death. Univariate Cox analysis of clinical and immunohistochemistry variables indicated that HER2/immunohistochemistry, number of involved nodes, progesterone receptor (PR)/immunohistochemistry (% cells), and ER/immunohistochemistry (% cells) were significantly associated with distant recurrence-free survival (DRFS). Univariate Cox analysis identified 22 genes associated with DRFS. Higher expression correlated with shorter DRFS for the HER2 adaptor GRB7 and the macrophage marker CD68. Higher expression correlated with longer DRFS for tumor protein p53-binding protein 2 (TP53BP2) and the ER axis genes PR and Bcl2. Multivariate methods, including stepwise variable selection and bootstrap resampling of the Cox proportional hazards regression model, identified several genes, including TP53BP2 and Bcl2, as significant predictors of DRFS.

Conclusion: Tumor gene expression profiles of archival tissues, some more than 20 years old, provide significant information about risk of distant recurrence even among patients with 10 or more nodes.




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Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Cell Growth & Differentiation
Copyright © 2005 by the American Association for Cancer Research.