Background: Breast cancer is a heterogeneous disease, presents various pathological signs such as axillary lymph node metastasis which is associated with a high risk of recurrence and considered as an important prognosis factor in the early stages of the disease.

Invasion and metastasis are two important hallmarks of malignant tumors caused by complex genetic and epigenetic alterations. The present study investigated the contribution of aberrant methylation profiles of cancer related genes, BRCA1, GSTP1, and, p16 (CDKN2A), in the sporadic Breast Cancer biopsy.

Patients and Methods: A total of 35 subjects, (7 healthy women with a family hystory of breast cancer and 26 with monolateral breast cancer) have been studied in order to detect the hypermethylation status of the promoter region of the following genes: p16, GSTP1 and BRCA1.

Results: The DNA methylation analysis of the candidate genes showed higher methylation proportion in the primary tumor tissue than that of the matched normal tissue and the differences were significant for the, BRCA1, and p16, promoter regions (p<0.05). Among those candidate methylated genes, BRCA1 and p16 displayed higher methylation proportion in the matched lymph node metastasis than that found in the normal tissue (p<0.05).

Conclusions: The results of the present study showed methylation heterogeneity between primary tumors and metastatic lesion. The pathway analysis revealed that, BRCA1 and p16 have a role in prevention of neoplasm metastasis. The contribution of aberrant methylation alterations of, BRCA1and p16 genes in lymph node metastasis might provide a further sign to establish useful biomarkers for screening metastasis. In summary, our DNA methylated assay performed from blood cells from BRCA1 carriers is able to predict breast cancer risk years in advance of diagnosis.