Tumor cell dissemination to the bone marrow and blood is associated with poor outcome in patients with metastatic breast cancer

The purpose of this study was to assess the impact of disseminated tumor cells (DTCs) on progression-free and overall survival (OS) in patients with metastatic breast cancer (MBC) and to compare it to simultaneous detection of circulating tumor cells (CTCs) from the blood in a subgroup. Disseminated tumor cells were identified in bone marrow (BM) aspirates by immunocytochemistry (pancytokeratin antibody A45-B/B3) and cytomorphology prior to the beginning of a new-line therapy. CTCs were enumerated by the CellSearch(A (R)) technology. BM was obtained from 178 patients with MBC; 64/178 (36 %) patients were DTC-positive. Disseminated tumor cells occurred more frequently in patients with visceral metastases (p = 0.020) and a parts per thousand yen2 lines of therapy (p = 0.017). CTCs were assessed in 33 of these patients and 17/33 (52 %) patients had CTC counts a parts per thousand yen5 CTCs/7.5 ml blood. There was no significant association between the DTC and CTC status. Univariate analysis revealed DTC detection as a significant predictor of poor OS (p < 0.001); median OS in DTC-negative versus DTC-positive patients was 52 [95 % confidence interval (CI) 38-67] versus 28 [95 % CI 19-37] months. Moreover, as described previously, patients with a parts per thousand yen5 CTCs/7.5 ml blood were at an increased risk of disease progression (p = 0.026) and death (p = 0.025). Disseminated tumor cells are predictors of poor prognosis in MBC, highlighting the role of tumor cell dissemination into the BM for breast cancer progression. The absence of a significant association between concurrent DTCs and CTCs suggests they might represent different aspects of systemic BC spread.