In the present study, we implemented the methylation signature of the 12 breast cancer candidate genes (APC, BIN1, BMP6, BRCA1, CST6, ESR-b, GSTP1, P14, P16, P21, PTEN and TIMP3) by comparing lymph nodes metastasis to their matched primary tumor tissues and normal tissues from the same breast cancer patients. Here, ESR2 is linked to breast cancer.