ArticlesGene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer
Introduction
About 60–70% of patients with lymph-node-negative breast cancer are cured by local or regional treatment alone.1, 2 The most widely used treatment guidelines are the St Gallen3 and the US National Institutes of Health4 consensus criteria. These guidelines recommend adjuvant systemic therapy for 85–90% of lymph-node-negative patients. There is a need for specific definition of an individual patient's risk of disease recurrence to ensure that she receives appropriate therapy. Currently, few diagnostic tools are available to identify at-risk patients. To date, gene-expression patterns have been used to classify breast tumours into clinically relevant subtypes.5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 We report a comprehensive genome-wide assessment of gene expression to identify broadly applicable prognostic markers.5, 6 In this study, we aimed to develop a gene-expression-based algorithm and to use it to provide quantitative predictions on disease outcome for patients with lymph-node-negative breast cancer.
Section snippets
Patients' samples
We selected from our tumour bank at the Erasmus Medical Center (Rotterdam, Netherlands) frozen tumour samples from patients with lymph-node-negative breast cancer who were treated during 1980–95, but who did not receive systemic neoadjuvant or adjuvant therapy. Tumour samples were submitted to our reference laboratory from 25 regional hospitals for measurements of steroid-hormone receptors. Guidelines for primary treatment were similar for all hospitals. Selection of tumours aimed to avoid
Results
The median follow-up for the 198 patients who survived was 101 months (range 20–171). Of the 286 patients included, 93 (33%) showed evidence of distant metastasis within 5 years and were counted as failures in analysis of distant-metastasis-free survival. Five (2%) patients died without evidence of disease and were censored at last follow-up. 83 (29%) died after previous relapse. Therefore, 88 patients (31%) were failures in the analysis of overall survival.
Clinical and pathological features of
Discussion
We provide results of an analysis of primary tumours from 286 patients with lymph-node-negative breast cancer of all age-groups and tumour sizes. The patients had not received adjuvant systemic therapy, so the multigene assessment of prognosis was not subject to potentially confounding contributions by predictive factors related to systemic treatment.
The study revealed a 76-gene signature that accurately predicts distant tumour recurrence. This signature could be applied to all
References (30)
- et al.
Predictive ability of DNA microarrays for cancer outcomes and correlates: an empirical assessment
Lancet
(2003) - et al.
Identification of high risk breast-cancer patients by gene-expression profiling
Lancet
(2002) - et al.
Gene expression predictors of breast cancer outcomes
Lancet
(2003) - et al.
Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer
Lancet
(2003) - et al.
Adhesion proteins in the biology of breast cancer: contribution of CD44
Exp Mol Pathol
(1999) Polychemotherapy for early breast cancer: an overview of the randomised trials
Lancet
(1998)Tamoxifen for early breast cancer: an overview of randomised trials
Lancet
(1998)- et al.
Meeting highlights: updated international expert consensus on the primary therapy of early breast cancer
J Clin Oncol
(2003) - et al.
National Institutes of Health Consensus Development Conference Statement: adjuvant therapy for breast cancer, Nov 1–3, 2000
J Natl Cancer Inst
(2001) - et al.
Gene expression profiles and molecular markers to predict recurrence of Dukes' B colon cancer
J Clin Oncol
(2004)