title: Monitoring of disseminated tumor cells in bone marrow in high-risk breast cancer patients treated with high-dose chemotherapy.
abstract: The present study aimed to investigate the clinical relevance of disseminated tumor cells (DTC) in breast cancer patients before and after high-dose adjuvant chemotherapy with or without progenitor stem-cell support. One hundred and eighteen high-risk stage II breast cancer patients entering the Scandinavian Study Group multicenter trial were randomized to 9 cycles of tailored and dose-escalated FEC (5-fluorouracil, epirubicin, cyclophosphamide) or 3 cycles of standard FEC followed by high-dose chemotherapy. Bone marrow (BM) samples at diagnosis and 6 months after completion of chemotherapy were assessed for the presence of cytokeratin positive (CK+) cells. Before treatment, 29% of the patients were CK+ (21% in the dose-escalated group and 36% in the high-dose-group). Six months after treatment, 17% of the patients were CK+ (17 and 16% respectively). Of the 95 patients who were evaluated 6 months after treatment, 60% were consistently CK-. CK+ cells in BM was evaluated as a prognostic and predictive marker and compared to other defined prognostic factors of the primary tumor. Monitoring BM changes at the time of diagnosis and 6 months posttreatment is an independent predictive factor for breast-cancer-specific survival (BCS) (p = 0.001). Those who have consistent CK negative (-) BM findings constitute a group of patients with good prognosis. Our results suggest that changes in CK+ cells in BM before and after chemotherapy can be used clinically as a surrogate maker to predict outcome in breast cancer patients.
authors.affiliation: Laboratory for Cellular Therapy, Department of Medical Oncology and Radiotherapy, The Norwegian Radium Hospital, University of Oslo, Oslo, Norway.
authors.forename: Vilde
authors.initials: V
authors.lastname: Drageset
authors.forename: Jahn M
authors.initials: JM
authors.lastname: Nesland
authors.forename: Bjorn
authors.initials: B
authors.lastname: Erikstein
authors.forename: Eva
authors.initials: E
authors.lastname: Skovlund
authors.forename: Hilde
authors.initials: H
authors.lastname: Sommer
authors.forename: Gun
authors.initials: G
authors.lastname: Anker
authors.forename: Erik
authors.initials: E
authors.lastname: Wist
authors.forename: Steinar
authors.initials: S
authors.lastname: Lundgren
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergh
authors.forename: Gunnar
authors.initials: G
authors.lastname: Kvalheim
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001854:Bone Marrow Cells; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D003520:Cyclophosphamide / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007633:Keratins / Q000032:analysis; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D015251:Epirubicin; D007633:Keratins; D003520:Cyclophosphamide; D005472:Fluorouracil