title: Association of CA27.29 and Circulating Tumor Cells Before and at Different Times After Adjuvant Chemotherapy in Patients with Early-stage Breast Cancer - The SUCCESS Trial.
abstract: Evidence for the prognostic value of circulating tumor cells (CTCs) in early-stage breast cancer is swiftly increasing. An alternative approach for identifying patients at risk for recurrence is based on the detection of the mucin-1 (MUC1)-based tumor marker CA27.29. Here we report the association of these two prognostic markers before and immediately after chemotherapy (CHT), as well as after 2 and 5 years of follow-up.
  
  
  
  The SUCCESS trial compared fluorouracil, epirubicin and cyclophosphamide followed by docetaxel vs. FEC followed by docetaxel plus gemcitabine, and 2 vs. 5 years of treatment with zoledronic acid in 3,754 patients with node-positive or high-risk node-negative early-stage breast cancer. CA27.29 was measured with the ST AIA-PACK CA27.29 reagent (Tosoh Bioscience, Belgium). The cutoff for CA27.29 positivity was >31 U/ml. CTCs were assessed with the CellSearch System (Veridex, USA). The cutoff for CTC positivity was ≥1 CTC/15 ml whole blood. The relationship between CTC positivity and CA27.29 positivity was assessed based on Chi-square statistics and Cramer's V, which varies from 0 (no association between the variables) to 1 (complete association). Samples for CA27.29 and CTC determinations during follow-up were only drawn from patients that had no relapse.
  
  
  
  Both CA27.29 and CTC data were available for 1,981, 1,602, 1,159 and 707 patients before, immediately after and at 2 and 5 years after CHT, respectively. Positivity rates for CTC were 21.3%, 22.8%, 18.6% and 8.5%, respectively. CA27.29 was positive in 7.9%, 21.0%, 2.8%and 7.5%, respectively. Positivity for both CA27.29 and CTC was found in 2.4%, 4.2%, 0.7% and 1.8% of patients, respectively. The association between CA27.29 and CTC was significant but weak before CHT (p=0.0015; Cramer's V=0.063) and 5 years after CHT (p<0.001; Cramer's V=0.164), and not significant immediately after CHT (p=0.162; Cramer's V=0.035) and 2 years after (p=0.349; Cramer's V=0.028).
  
  
  
  We showed that CTC and CA27.29 positivity were significantly, but only weakly associated before CHT and 5 years after CHT, while no significant association was found immediately or 2 years after CHT during the course of early-stage breast cancer. It, therefore, seems reasonable to further evaluate the prognostic value of CTCs and CA27.29 as a combined prognostic test of two potentially independent markers that might provide complementary prognostic information.
authors.affiliation: Department of Gynecology and Obstetrics, HELIOS University Hospital Wuppertal, University Witten/Herdecke, Wuppertal, Germany philip.hepp@helios-kliniken.de.
authors.forename: Philip
authors.initials: P
authors.lastname: Hepp
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Ludwig-Maximilian University, Munich, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Andergassen
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Jäger
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Ludwig-Maximilian University, Munich, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Trapp
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Ludwig-Maximilian University, Munich, Germany.
authors.forename: Marianna
authors.initials: M
authors.lastname: Alunni-Fabbroni
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Ulm, Ulm, Germany.
authors.forename: Thomas W P
authors.initials: TW
authors.lastname: Friedl
authors.affiliation: Joint practice for Gynecology and Obstetrics, Braunschweig, Germany.
authors.forename: Nadeschda
authors.initials: N
authors.lastname: Hecker
authors.affiliation: Joint practice for Gynecology and Obstetrics, Braunschweig, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Lorenz
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Friedrich-Alexander University, Erlangen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Fasching
authors.affiliation: National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany: SUCCESS Studiengruppe.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schneeweiss
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Fehm
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Ulm, Ulm, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Janni
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Ludwig-Maximilian University, Munich, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Rack
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D000077143:Docetaxel; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood*; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000473:pathology*; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011379:Prognosis; D043823:Taxoids / Q000008:administration & dosage; D000093542:Gemcitabine
chemical_list: D014408:Biomarkers, Tumor; C060192:MUC1 protein, human; D018396:Mucin-1; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D015251:Epirubicin; D003520:Cyclophosphamide; D005472:Fluorouracil; D000093542:Gemcitabine
keywords: Tumor marker; adjuvant; breast cancer; minimal residual disease