title: Tumor cell dissemination to the bone marrow and blood is associated with poor outcome in patients with metastatic breast cancer.
abstract: 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® 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 ≥2 lines of therapy (p = 0.017). CTCs were assessed in 33 of these patients and 17/33 (52 %) patients had CTC counts ≥5 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 ≥5 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.
authors.affiliation: Department of Obstetrics and Gynecology, University of Tuebingen, Calwerstraße 7, 72076, Tuebingen, Germany, andreas.hartkopf@med.uni-tuebingen.de.
authors.forename: Andreas D
authors.initials: AD
authors.lastname: Hartkopf
authors.forename: Diana
authors.initials: D
authors.lastname: Stefanescu
authors.forename: Markus
authors.initials: M
authors.lastname: Wallwiener
authors.forename: Markus
authors.initials: M
authors.lastname: Hahn
authors.forename: Sven
authors.initials: S
authors.lastname: Becker
authors.forename: Erich-Franz
authors.initials: EF
authors.lastname: Solomayer
authors.forename: Tanja N
authors.initials: TN
authors.lastname: Fehm
authors.forename: Sara Y
authors.initials: SY
authors.lastname: Brucker
authors.forename: Florin-Andrei
authors.initials: FA
authors.lastname: Taran
mesh_terms: D001853:Bone Marrow / Q000473:pathology*; D001943:Breast Neoplasms / Q000097:blood* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D009367:Neoplasm Staging / Q000379:methods; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011379:Prognosis