Homocysteine as a Biomarker for Predicting Disease-Free Survival in Breast Cancer

Daniela Filippini Ierardi¹, Luis Gustavo Raimundo², Gimena Aguiar¹, Patrícia Bandeira Rueda Germano³, Luiz Henrique Gebrim^4,5, Nelson Carvas⁶, Bruno Frederico Aguilar Calegare⁶, Vânia D’Almeida⁶, Catarina Segreti Porto¹, Miriam Galvonas Jasiulionis^1,3*, Mariangela Correa^2,7

¹Departamento de Farmacologia, Universidade Federal de Sao Paulo, Sao Paulo, Brazil.
²Instituto do Cancer do Estado de Sao Paulo, Sao Paulo, Brazil.
³Disciplina de Imunologia, Universidade Federal de Sao Paulo, Sao Paulo, Brazil.
⁴Centro de Referência da Saúde da Mulher, Hospital Pérola Byington, Sao Paulo, Brazil.
⁵Disciplina de Mastologia, Universidade Federal de Sao Paulo, Sao Paulo, Brazil.
⁶Departamento de Psicobiologia, Universidade Federal de Sao Paulo, Sao Paulo, Brazil.
⁷Instituto de Educacao e Ciência, Hospital Alemao Oswaldo Cruz, Sao Paulo, Brazil.

DOI: 10.4236/abcr.2013.22006                

Abstract

Introduction: Breast cancer is the leading cause of cancer mortality among women. Some biomarkers and clinical features are used for the diagnosis and prognosis of this tumor, but no prognostic or predictive marker is routinely available specifically for hormone receptor positive tumors. Homocysteine is well known as a risk factor in atherosclerotic vascular diseases, but its participation in cancer biology is still unclear. The aim of this study was to evaluate serum Homocysteine and Cysteine as biomarkers of disease progression in breast tumor. As a secondary objective, the effect of a short course (one month) of hormonal treatment on Homocysteine, Cysteine and DNA methylation levels was also evaluated. Methods: Blood samples, tumor samples and normal adjacent tissue were collected during the initial biopsy (pre-treatment) and after one month of hormonal therapy (post-treatment). Serum Homocysteine and Cysteine were analyzed by HPLC and tissue global DNA methylation was determined by the Methylation-Sensitive Restriction Enzyme (MSRE) technique. Results: Variations in Homocysteine levels were significantly correlated with Disease-Free Survival. Cox proportional risk model demonstrated that nodal status and Homocysteine levels were independent prognostic factors for disease-free survival (DFS). A significant difference was observed between pre-and post-treatment levels of Homocysteine and Cysteine in advanced tumors, suggesting a prognostic role in patients with poor clinical characteristics. Conclusion: Although more studies are needed to confirm these results, our research suggests that Hcy might be used as a prognostic biomarker for breast cancer.

Keywords

Homocysteine; Cysteine; Breast Cancer; Estrogen Receptor; Prognostic and Predictive Biomarker; Tamoxifen; Anastrozol

Conflicts of Interest

The authors declare no conflicts of interest.

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