An 8-gene qRT-PCR-based gene expression score that has prognostic value in early breast cancer

Iker Sánchez-Navarro¹^†, Angelo Gámez-Pozo¹^†, Álvaro Pinto², David Hardisson³, Rosario Madero⁴, Rocío López¹, Belén San José⁴, Pilar Zamora², Andrés Redondo², Jaime Feliu², Paloma Cejas¹, Manuel González Barón^2,⁵, Juan Ángel Fresno Vara¹^* and Enrique Espinosa²^*

* Corresponding authors: Juan Ángel Fresno Vara jafresno@gmail.com - Enrique Espinosa eespinosa00@terra.es
† Equal contributors

Author Affiliations

¹ Unidad de Investigación, Instituto de Investigación Sanitaria IdIPAZ, Hospital Universitario La Paz (Paseo de la Castellana, 261), Madrid (28046), Spain
² Service of Oncology, IdIPAZ, Hospital Universitario La Paz (Paseo de la Castellana, 261), Madrid (28046), Spain
³ Service of Pathology, IdIPAZ, Hospital Universitario La Paz (Paseo de la Castellana, 261), Madrid (28046), Spain
⁴ Service of Statistics, IdIPAZ, Hospital Universitario La Paz (Paseo de la Castellana, 261), Madrid (28046), Spain
⁵ Chair of Oncology & Palliative care, Facultad de Medicina, Universidad Autónoma de Madrid (Arzobispo Morcillo n° 2 y 4), Madrid (28029), Spain

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BMC Cancer 2010, 10:336 doi:10.1186/1471-2407-10-336

The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2407/10/336

Received:	30 October 2009
Accepted:	28 June 2010
Published:	28 June 2010

© 2010 Sánchez-Navarro et al; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Gene expression profiling may improve prognostic accuracy in patients with early breast cancer. Our objective was to demonstrate that it is possible to develop a simple molecular signature to predict distant relapse.

Methods

We included 153 patients with stage I-II hormonal receptor-positive breast cancer. RNA was isolated from formalin-fixed paraffin-embedded samples and qRT-PCR amplification of 83 genes was performed with gene expression assays. The genes we analyzed were those included in the 70-Gene Signature, the Recurrence Score and the Two-Gene Index. The association among gene expression, clinical variables and distant metastasis-free survival was analyzed using Cox regression models.

Results

An 8-gene prognostic score was defined. Distant metastasis-free survival at 5 years was 97% for patients defined as low-risk by the prognostic score versus 60% for patients defined as high-risk. The 8-gene score remained a significant factor in multivariate analysis and its performance was similar to that of two validated gene profiles: the 70-Gene Signature and the Recurrence Score. The validity of the signature was verified in independent cohorts obtained from the GEO database.

Conclusions

This study identifies a simple gene expression score that complements histopathological prognostic factors in breast cancer, and can be determined in paraffin-embedded samples.