Abstract Metastasis is the most life-threatening sequel in breast cancer (BC). The aim of the study is to assess the association of certain cytokines including IL4, IL-11, CCL-2, CCL-4, and CXCL12 with the site of metastases (lung, bone, brain, ovaries, and liver) in BC. The serum levels of IL4, IL-11, CCL-2, CCL4 and CXCL-12 were assessed in 175 BC patients compared to 50 control subjects using ELISA. The data were correlated to the sites of metastases, patients’ clinicopathological features and response to treatment. The mean age of the BC patients was 49.3 ± 9.5 years old. Distant metastasis was found in 69.1% (121/175) of the patients. There was a significant increase in IL4 ( p = 0.012 ), CXCL12 ( p < 0.001 ), and CCL4 ( p < 0.001 ) in BC patients compared to controls. Lung metastasis associated significantly with increased IL11 concentration (OR = 1.008, p = 0.023). Brain metastasis associated with increased IL4 (OR = 1.009, p = 0.025), and CXCL12 concentrations (OR = 1.004, p = 0.031). Bone metastasis linked with CCL4 (OR = 0.991, p = 0.017) and CCL2 (OR = 0.996, p = 0.001). Low ER expression, brain, and liver metastasis were considered as potential independent risk factors for shorter disease-free survival (DFS) of BC patients ( p = 0.040 , 0.001 , and 0.003 ; respectively). IL4 (AUC = 0.699, p = 0.011) and CXCL12 (AUC = 0.700, p = 0.010) showed a diagnostic potential for BC brain metastasis. Combined expression of both IL4 and CXCL12 exhibited a 75% sensitivity and a 71.4% specificity (AUC = 0.768, p = 0.001). IL11 associated with the diagnosis of BC lung metastasis (AUC = 0.629, p = 0.024). While CCL2 showed a significant potential for the diagnosis of BC liver metastasis (AUC = 0.717, p = 0.006). Chemokines have an important role in directing the tumor cells and colonization in a specific metastatic site.
Ayoub et al. (2026) studied this question.