TITLE:
Homocysteine as a Biomarker for Predicting Disease-Free Survival in Breast Cancer
AUTHORS:
Daniela Filippini Ierardi, Luis Gustavo Raimundo, Gimena Aguiar, Patrícia Bandeira Rueda Germano, Luiz Henrique Gebrim, Nelson Carvas, Bruno Frederico Aguilar Calegare, Vânia D’Almeida, Catarina Segreti Porto, Miriam Galvonas Jasiulionis, Mariangela Correa
KEYWORDS:
Homocysteine; Cysteine; Breast Cancer; Estrogen Receptor; Prognostic and Predictive Biomarker; Tamoxifen; Anastrozol
JOURNAL NAME:
Advances in Breast Cancer Research,
Vol.2 No.2,
April
29,
2013
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.