Abstract 115: Correlation between homocysteine concentration in serum and response to anti-hormonal treatment in breast tumor patients
Authors: Daniela F. Ierardi, Patricia B M R Germano, Gimena Aguiar, Luis Gustavo Raimundo, Andre Mattar, Vânia D'Almeida, Bruno Calegari, Catarina Porto, Luis Henrique Gebrim, Mariangela Correa, Miriam G. Jasiulionis
Journal: Cancer Research (2011)

Abstract Background: Breast tumors are today the most incident tumor in women. One of the widely used markers for breast cancer is the estrogen receptor (ER), which is member of the nuclear receptor superfamily of transcription factors. Almost 70% of the breast cancer patients are ER positive and can be beneficiated with hormonal therapy. Patients with ER+ tumors are candidates for anti-hormonal therapy, including tamoxifen and anastrozol. Many studies proposed that elevated levels of total homocysteine (tHcy) in the blood can be a risk factor for cancer. It is also known that estrogen status is associated with tHcy concentration. One important epigenetic mechanism which is a well-described for carcinogenesis, and seems to be related to homocysteine pathways, is the DNA methylation. In tumors, it is well documented a decrease in total DNA methylation and a hipermethylation of specific gene promoters. There are no studies showing the impact of anti-hormonal treatment in the tHcy concentration and in the DNA methylation pattern of the breast tumor patients. Objectives: In this study we aimed to verify which is the impact of the anti-hormonal treatment in the tHcy concentration and its correlation with the clinical data. Samples and Methods: To investigate the effect of anti-hormonal therapy on homocysteine metabolism, 50 breast tumor patients were randomly assigned to therapy with anastrozol or tamoxifen or placebo. Sera from the patients were obtained before and after the treatment with anti-hormonal drugs. Homocysteine levels were determined by HPLC. Total DNA methylation was evaluated in the tumor biopsies before the treatment by restriction enzyme method. Pearson's correlation test and t test were performed for statistical analysis. Results: We observed that the tHcy before the anti-hormonal treatment increase in the patients with a high agressive tumor (p=0,0401), and with positive lifonodes (p=0,0379). After the treatment with tamoxifen, the tHcy level decreases (p=0,0263). We could observe that the decrease was significant in the patients with positive linfonodes (p=0,0400). No significant correlations were observed when the patients were treated with anastrozol or placebo and also no correlation were observed in these patients when we correlated the tHcy variation with the clinical data set. We observed a total DNA hypomethylation in the tumors before treatment when compared with adjacent tissue (p=0,0157). Conclusions and perspectives: We could observe that the higher tHcy levels are related to aggressive tumors. Our results also show that the treatment with tamoxifen, mainly in aggressive tumors, decreases the tHcy levels showing that this treatment can have a role in the tHcy level. Other clinical data and new studies should be done to evaluate the tamoxifen impact in tHcy and also its relation with the tumor DNA methylation. Financial support: Fapesp, CAPES, CNPq. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 115. doi:10.1158/1538-7445.AM2011-115