title: Clinical significance of proliferative potential of occult metastatic cells in bone marrow of patients with breast cancer.
abstract: There is increasing statistical evidence that the presence of tumour cells in bone marrow detected by immunocytochemistry represents an important prognostic indicator in breast cancer, but their individual capacity to become clinical metastases is unknown. The aim of this study was to assess the proliferative capacity of these occult metastatic cells in the bone marrow of patients with various stages of breast cancer. We obtained bone marrow aspirates from 60 patients with breast cancer before treatment with chemotherapy: 17 stage II, 12 stage III and 31 stage IV. After bone marrow culture for 6-34 days (median: 17 days) under specific cell culture conditions, viable epithelial cells were detected by cytokeratin staining in 40 patients (66%). Expansion of tumour cells was poorly correlated with tumour cell detection on primary screening (P=0.06). There was a nonsignificant correlation between the number and the presence of expanded tumour cells and the UICC stage of the patients. On primary screening, tumour cell detection was positive in 56% of patients and was correlated with clinical UICC stage (P=0.01). However, with a median follow-up of 23 months, expansion of tumour cells from bone marrow was associated with decreased patient survival (P=0.04), whereas the survival difference according to detection of CK-positive cells on primary screening was not statistically significant. In conclusion, viable tumour cells can be detected in the bone marrow of breast cancer patients. Their proliferative potential could be predictive of outcome and deserves further investigation.
authors.affiliation: Medical Oncology Department, Institut Curie, 75248 Paris Cedex 05, France. jean-yves.pierga@curie.net
authors.forename: J-Y
authors.initials: JY
authors.lastname: Pierga
authors.forename: C
authors.initials: C
authors.lastname: Bonneton
authors.forename: H
authors.initials: H
authors.lastname: Magdelénat
authors.forename: A
authors.initials: A
authors.lastname: Vincent-Salomon
authors.forename: C
authors.initials: C
authors.lastname: Nos
authors.forename: P
authors.initials: P
authors.lastname: Pouillart
authors.forename: J-P
authors.initials: JP
authors.lastname: Thiery
mesh_terms: D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000556:secondary*; D001943:Breast Neoplasms / Q000209:etiology / Q000473:pathology*; D018929:Cell Culture Techniques; D002455:Cell Division; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis