title: Detection of disseminated tumor cells in locally advanced breast cancer patients before primary systemic therapy.
abstract: OBJECTIVE
  To assess the prevalence and prognostic power of disseminated tumor cells (DTC) in patients with locally advanced breast cancer (LABC) before primary systemic therapy (PST).
  
  
  METHODS
  LABC patients attending our Breast Unit were studied between 2002 and 2012, all of them being considered for PST. To determine the presence of DTC, posterior iliac crest aspirates were obtained and marrow samples were processed by gradient separation with Ficoll (Lymphoprep(®)) and immunohistochemical staining using the antiCK A45-B/B3 (EPIMET) antibody. Clinicopathologic variables were recorded before and after PST to assess response. Disease-free survival (DFS) and overall survival (OS) were determined after follow-up. The presence of DTC as a predictor of response to PST and as a prognostic tool for OS and DSF was evaluated.
  
  
  RESULTS
  DTC were observed in 26% of 47 patients included in the study. PST consisted of chemotherapy in 94% and hormone therapy in 6%. Breast-conserving therapy was attained in 33%. Mean follow-up was 68 months. Complete clinical response (CR) after PST was seen in 26%, disease recurrence in 38%, and cancer-related death in 8%; tumor size and negative estrogen receptors were significant predictors of CR and mastectomy was associated with DFS. Persistent axillary disease after PST and previous recurrence were predictive of OS. DTC were detected more often in patients who did not achieve CR and those who presented recurrence. DTC detection was a significant prognostic factor for a worse OS (OR = 7.62; CI95%: 1.46-39.61; p = 0.009) and a decreased survival time (62 versus 82 months, p = 0.004).
  
  
  CONCLUSIONS
  Presence of DTC before PST was found in a significant number of patients with LABC. DTC were found to be a significant prognostic factor for cancer-related death. DTC could be a surrogate predictor of response to PST and also of disease recurrence in LABC patients.
authors.affiliation: Nuclear Medicine Department, Germans Trias i Pujol University Hospital, Carretera del Canyet, Badalona, Spain. Electronic address: msola.germanstrias@gencat.cat.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Solá
authors.forename: Mireia
authors.initials: M
authors.lastname: Margelí
authors.forename: Eva
authors.initials: E
authors.lastname: Castellá
authors.forename: Beatriz
authors.initials: B
authors.lastname: Cirauqui
authors.forename: Antonio
authors.initials: A
authors.lastname: Mariscal
authors.forename: Miquel
authors.initials: M
authors.lastname: Rull
authors.forename: Juan F
authors.initials: JF
authors.lastname: Julian
authors.forename: Miquel
authors.initials: M
authors.lastname: Luna
authors.forename: Virginia
authors.initials: V
authors.lastname: Vallejo
authors.forename: Manuel
authors.initials: M
authors.lastname: Fraile
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001365:Axilla; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D002277:Carcinoma / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008408:Mastectomy; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D009360:Neoplastic Cells, Circulating; D018714:Radiotherapy, Adjuvant; D043823:Taxoids / Q000008:administration & dosage; D000068878:Trastuzumab
chemical_list: D018943:Anthracyclines; D061067:Antibodies, Monoclonal, Humanized; D018931:Antineoplastic Agents, Hormonal; D043823:Taxoids; D000068878:Trastuzumab
keywords: Bone marrow; CR; CTC; DCIS; DFS; DTC; Disseminated tumor cells; ISHAGE; International Society of Hematotherapy and Graft Engineering; LABC; Locally advanced breast cancer; Neoadjuvant chemotherapy; OR; OS; PST; Primary systemic therapy; RR; circulating tumor cells; complete clinical response; disease-free survival; disseminated tumor cells; ductal carcinoma in situ; locally advanced breast cancer; odds ratio; overall survival; primary systemic treatment; relative risk