Bone marrow versus sentinel lymph node involvement in breast cancer: A comparison of early hematogenous and early lymphatic tumor spread

The early spread of tumor cells in primary breast cancer patients may occur either through lymphatic or hematogenous dissemination. Lymph node (LN) status and presence of disseminated tumor cells (DTC) in bone marrow (BM) are independent predictors of poor outcome. It is unknown which factors determine one or the other route of tumor cell spread and whether lymphatic and hematogenous tumor cell dissemination are two independent processes. This study is aimed to compare the DTC status in clinically node-negative (N0) breast cancer patients with their sentinel LN status and to investigate predictors of BM and LN involvement. The DTC status of 1,345 clinically N0 breast cancer patients who underwent SLN biopsy during initial surgery was investigated. BM and LN status were compared and predictors of hematogenous and lymphatic tumor cell spread were investigated. DTCs were present in the BM of 181 (13%) patients. LN involvement was found in 348 (26%) patients. There was no correlation between LN and BM status: 137 of 997 nodal-negative patients (14%) had BM involvement and 44 of 348 nodal-positive patients (13%) were positive for DTCs (P = 0.649). The presence of DTCs was not influenced by tumorbiological factors. Conversely, a high correlation between nodal status and tumor size, histology, ER-status and lymph vessel invasion was found. Hematogenous and lymphatic tumor spread seem to be because of independent pathways of cancer progression.