Immunocytochemical detection of epithelial cells in the bone marrow of primary breast cancer patients: a meta-analysis

Purpose. The immunocytochemical detection of epithelial cells in the bone marrow (BM) of breast cancer (BC) patients has been shown to have prognostic importance in several studies. We conducted a systematic review of the literature and a meta-analysis to assess the specificity, rate of positivity and correlation with known prognostic variables as well as with disease free (DFS) and overall survival (OS). Design. We performed a systematic review from the published literature. We included studies with at least 20 previously untreated BC patients as well as non-BC controls that evaluated the presence of epithelial cells in BM using immunocytochemistry (IC). Results. We identified 14 eligible studies with 3253 BC patients and 532 controls. Our results showed that IC has an overall rate of positivity of 31% (95% CI: 30 - 33%), and specificity of 96% ( compared to normal patients) ( 95% CI: 0.94 - 0.98). We observed significant direct correlations between IC BM positivity and the primary tumor's presence with expression of estrogen receptors, larger size and higher histologic grade as well as with the presence of more than 3 positive axillary lymph nodes. At 5 years of follow up IC positivity correlated directly with a lower DFS ( relative risk = 1.60; 95% CI: 1.39 - 1.83) and OS ( relative risk = 1.73; 95% CI: 1.29 - 2.31). The prognostic impact of BM positivity seemed to decrease with time. Conclusions. We conclude that the finding of epithelial cells in BM of BC patients correlates with several known prognostic factors and has adverse impact in the DFS and OS of these patients that seems, however, to decrease with time.