Results of this study revealed that 70% of primary breast cancer tissues and 77% of metastasis cancer cells in lymph nodes expressed CCR7. in tumor cells with lymph node (LN) metastasis. Similarly, EGFR was expressed highly in tumors with LN metastasis. The ligands were especially expressed in metastatic tumors than in primary tumors from the same patients. Moreover, the expression of both CXCR4 accompanied by CCR7 and CXCL12 accompanied by CCL21 were up-regulated. Kaplan-Meier survival analysis revealed that patients exhibiting high CXCR4, CCR7, and EGFR expression experienced a shorter survival period compared with those with low expression. == Conclusions == The expression of CXCR4, CCR7, and EGFR may be associated with LN metastasis. Moreover, the expression of these receptors can serve as an indicator of undesirable prognosis in patients with breast cancer. == Background == Breast cancer ranks among the most common malignant tumors afflicting women worldwide. Despite decreased mortality rates resulting from combined therapy, breast cancer remains a leading cause of cancer death in women. Particularly FTSJ2 in the last two decades, incidence and mortality rates of breast cancer have climbed sharply in China, thus attracting increased attention from researchers. Metastasis is usually one characteristic of malignant tumors which determines the course of therapy and cancer prognosis. It is a multifactorial, nonrandom, and sequential process with an organ-selective characteristic. In essence, axillary lymph node metastasis is Mitoquinone the most frequently occurring metastatic disease; it can be seen as a surrogate for distant metastasis and long-term survival [1]. Although several molecules are involved in breast cancer metastasis, precise mechanism of tumor cell migration Mitoquinone to specific organs remains to be established [2]. Previously, the “seed and soil” theory was employed to explain directional metastasis, considering that certain metastasis organs possess the congenial environment of the primary organ [3]. More recently, a “chemokine-receptor” model has been proposed to explain the homing of tumor cells to specific organs [4]. Chemokines belong to a super-family of small, cytokine-like proteins that induce cytoskeletal rearrangement and adhesion to endothelial and directional migration through their conversation with G-protein-coupled receptors [2,5]. Among the chemokines, the most interesting chemokine-receptor pair is the CXC chemokine receptor-4 (CXCR4) and its lone ligand, CXC chemokine ligand-12 (CXCL12). Muller exhibited that CXCR4 is usually consistently expressed in human breast cancer cells, malignant breast tumor and metastasis tumors, while its ligand CXCL12 is usually preferentially expressed in the lungs, liver, bone marrow, and lymph nodes [2]. Thus, it can be deduced that this CXCL12-CXCR4 axis may be associated with the metastasis of breast cancer cells to the lungs, liver, Mitoquinone bone, and lymph nodes. Unlike CXCL12, however, CC chemokine ligand-21 (CCL21) – the ligand for CC chemokine receptor-7 (CCR7) – is usually highly expressed in the lymph nodes of breast cancer patients [5]. Thus, the CCR7-CCL21 axis can be said to assume an important role in lymph node metastasis [6]. In this study, the expression of both CXCR4 and CCR7 is usually combined to evaluate their contribution in the lymph node metastasis of breast cancer. The importance of growth factors such as epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor2 (HER-2/neu) has been established in the prognosis of breast cancer. Recently, several studies have revealed the crosstalk between CXCR4 and EGFR or HER-2/neu through transactivation by the CXCL12-CXCR4 axis. This study aims to verify the significance of CXCR4, CCR7 and their CXCL12 and CCL21 ligands, together with EGFR in the evaluation of metastasis and the prognosis of breast cancer. == Methods == == Patient selection and clinical data == The study group was composed of 200 specimens selected from 284 cases (84 cases were excluded owing to the absence of follow-up status) of female primary invasive duct breast cancer cases diagnosed between January 1997 and December 2004 at the General Hospital of Tianjin Medical University. Patients’ records were retrieved and clinical data, histopathological record, and treatment information were all reviewed. All patients had not been subjected to chemotherapy and radiotherapy prior to surgical resection but had received chemotherapy Mitoquinone following surgical operation. Follow-up information from all the patients were obtained by the authors themselves in August 2009 through visits or telephone interviews with either the patients or their relatives. Mean follow-up time was 88 months, ranging from 5 to 150 months. Formalin-fixed paraffin-embedded tumor materials and their lymph.