title: Disseminated tumor cells as selection marker and monitoring tool for secondary adjuvant treatment in early breast cancer. Descriptive results from an intervention study.
abstract: BACKGROUND
  Presence of disseminated tumor cells (DTCs) in bone marrow (BM) after completion of systemic adjuvant treatment predicts reduced survival in breast cancer. The present study explores the use of DTCs to identify adjuvant insufficiently treated patients to be offered secondary adjuvant treatment intervention, and as a surrogate marker for therapy response.
  
  
  METHODS
  A total of 1121 patients with pN1-3 or pT1c/T2G2-3pN0-status were enrolled. All had completed primary surgery and received 6 cycles of anthracycline-containing chemotherapy. BM-aspiration was performed 8-12 weeks after chemotherapy (BM1), followed by a second BM-aspiration 6 months later (BM2). DTC-status was determined by morphological evaluation of immunocytochemically detected cytokeratin-positive cells. If DTCs were present at BM2, docetaxel (100 mg/m², 3qw, 6 courses) was administered, followed by DTC-analysis 1 month (BM3) and 13 months (BM4) after the last docetaxel infusion.
  
  
  RESULTS
  Clinical follow-up (FU) is still ongoing. Here, the descriptive data from the study are presented. Of 1085 patients with a reported DTC result at both BM1 and BM2, 94 patients (8.7%) were BM1 positive and 83 (7.6%) were BM2 positive. The concordance between BM1 and BM2 was 86.5%. Both at BM1 and BM2 DTC-status was significantly associated with lobular carcinomas (p = 0.02 and p = 0.03, respectively; chi-square). In addition, DTC-status at BM2 was also associated with pN-status (p = 0.009) and pT-status (p = 0.03). At BM1 28.8% and 12.8% of the DTC-positive patients had ≥2 DTCs and ≥3 DTCs, respectively. At BM2, the corresponding frequencies were 47.0% and 25.3%. Of 72 docetaxel-treated patients analyzed at BM3 and/or BM4, only 15 (20.8%) had persistent DTCs. Of 17 patients with ≥3 DTCs before docetaxel treatment, 12 patients turned negative after treatment (70.6%). The change to DTC-negativity was associated with the presence of ductal carcinoma (p = 0.009).
  
  
  CONCLUSIONS
  After docetaxel treatment, the majority of patients experienced disappearance of DTCs. As this is not a randomized trial, the results can be due to effects of adjuvant (docetaxel/endocrine/trastuzumab) treatment and/or limitations of the methodology. The clinical significance of these results awaits mature FU data, but indicates a possibility for clinical use of DTC-status as a residual disease-monitoring tool and as a surrogate marker of treatment response.
  
  
  BACKGROUND
  Clin Trials Gov NCT00248703.
authors.affiliation: Department of Oncology, Oslo University Hospital, Radiumhospitalet, Oslo, Norway.
authors.forename: Marit
authors.initials: M
authors.lastname: Synnestvedt
authors.forename: Elin
authors.initials: E
authors.lastname: Borgen
authors.forename: Erik
authors.initials: E
authors.lastname: Wist
authors.forename: Gro
authors.initials: G
authors.lastname: Wiedswang
authors.forename: Kjetil
authors.initials: K
authors.lastname: Weyde
authors.forename: Terje
authors.initials: T
authors.lastname: Risberg
authors.forename: Christian
authors.initials: C
authors.lastname: Kersten
authors.forename: Ingvil
authors.initials: I
authors.lastname: Mjaaland
authors.forename: Lise
authors.initials: L
authors.lastname: Vindi
authors.forename: Cecilie
authors.initials: C
authors.lastname: Schirmer
authors.forename: Jahn Martin
authors.initials: JM
authors.lastname: Nesland
authors.forename: Bjørn
authors.initials: B
authors.lastname: Naume
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001853:Bone Marrow / Q000473:pathology*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000473:pathology* / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008875:Middle Aged; D018365:Neoplasm, Residual; D043823:Taxoids / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel