The pattern of chemokine receptors expressed by tumor cells predicts the site of metastatic relapse in patients with axillary node positive breast cancer

Abstract

9501 Background: Some types of tumors present an organ-specific pattern of metastases. Although studies performed in animal models present strong evidence for a role of chemokine receptors in this phenomenon, there is no clinical study that specifically correlates the pattern of chemokine receptor expression with the site of metastases. In the present study, we have looked at the correlation between the chemokine receptors expressed by primary tumor cells and the site of metastatic relapse in patients with T1–3N+M0 breast cancer. Methods: CX3CR1, CXCR4, CCR6 and CCR7 expressions were evaluated by immunohistochemistry on primary tumors obtained from 142 patients with T1–3N+M0 breast cancer. These patients were included in a prospective trial between 1972 and 1979. None of the patients received adjuvant chemotherapy. Results: CX3CR1, CXCR4, CCR6, CCR7 expressions were found in 59 (43%), 42 (31%), 45 (34%) and 93 (66%) patients respectively. The expression of chemokine receptors did not correlate with any clinical characteristics, except a higher rate of very young patients (<35 year) in the CXCR4+ subgroup (14% vs 4%, p=0.04). After a median follow-up of 25 years, 75 patients (53%) have presented a metastatic relapse. The expression of chemokine receptors did not predict the metastasis-free survival, nor the overall survival. On the other hand, the pattern of chemokine receptor expression predicted the site of metastatic relapse. CX3CR1 staining predicted the occurence of brain metastases (14% vs 1%, p=0.004). CXCR4 staining predicted the occurrence of liver metastases (38% vs 14%, p=0.001) and lung metastases (28% vs 16%, p=0.05). CCR7 predicted the occurrence of skin metastases (11% vs 0%, p=0.03) and CCR6 predicted the occurrence of malignant pleural effusion (24% vs 10%, p=0.04). Conclusion: The study shows that the pattern of chemokine receptors expressed by tumor cells predicts the site of metastatic relapse in patients with T1–3N+M0 breast cancer. This study, in line with data obtained in animal models, may suggest in a clinical model that the chemokine receptor family could be the biological support of the << seed and soil >> theory. No significant financial relationships to disclose.