title: Disseminated tumor cells as a monitoring tool for adjuvant therapy in patients with primary breast cancer.
abstract: The presence of disseminated tumor cells (DTC) in the bone marrow (BM) of early breast cancer patients at initial surgery as well as during follow-up predicts an unfavorable outcome. This study aimed to assess whether adjuvant systemic therapy has the ability to eradicate DTC and to determine the clinical impact of DTC-persistence. Between 12 and 24 months after an initial BM aspiration during primary surgery (BMA1) a second and third bone marrow aspiration (BMA2 and BMA3, respectively) was performed. DTC were identified by immunocytochemistry (pancytokeratin antibody A45-B/B3) and cytomorphology. A total of 190 patients who were DTC-positive at BMA1 were eligible for this retrospective analysis. DTC persisted in 35 of 190 (19 %) patients at BMA2 and in 11 of 71 (16 %) patients at BMA3. DTC-persistence at BMA3 was significantly lower in patients that received adjuvant endocrine therapy (p = 0.017). At BMA2, DTC-positive patients were at an increased risk of disease recurrence (HR: 4.17, 95 % CI: 1.51-11.50, p = 0.003) and death (HR: 5.02, 95 % CI: 1.156-21.83, p = 0.031). At BMA3, the presence of DTC was associated with shorter disease free survival (HR: 3.20, 95 % CI: 1.05-9.78, p = 0.010). In conclusion, a majority of initially DTC-positive primary breast cancer patients turned negative during adjuvant treatment. As DTC-persistence predicted an adverse outcome, serial DTC-determination can identify patients that will probably benefit from additional or a switch of adjuvant therapy.
authors.affiliation: Department of Obstetrics and Gynecology, University of Tuebingen, Calwerstrasse 7, 72076, Tübingen, Germany, ines.gruber@med.uni-tuebingen.de.
authors.forename: Ines
authors.initials: I
authors.lastname: Gruber
authors.forename: Tanja
authors.initials: T
authors.lastname: Fehm
authors.forename: Florin Andrei
authors.initials: FA
authors.lastname: Taran
authors.forename: Markus
authors.initials: M
authors.lastname: Wallwiener
authors.forename: Markus
authors.initials: M
authors.lastname: Hahn
authors.forename: Diethelm
authors.initials: D
authors.lastname: Wallwiener
authors.forename: Natalia
authors.initials: N
authors.lastname: Krawzyck
authors.forename: Juergen
authors.initials: J
authors.lastname: Hoffmann
authors.forename: Andreas Daniel
authors.initials: AD
authors.lastname: Hartkopf
mesh_terms: D001853:Bone Marrow / Q000473:pathology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D045744:Cell Line, Tumor; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D061986:MCF-7 Cells; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D012189:Retrospective Studies