Single circulating tumor cell detection and overall survival in nonmetastatic breast cancer

Ann Oncol. 2010 Apr;21(4):729-733. doi: 10.1093/annonc/mdp391. Epub 2009 Oct 22.

Abstract

Background: Circulation of cancer cells in the blood is a mandatory step for metastasis, but circulating tumor cells (CTC) have a low metastatic efficiency in preclinical animal models. In this prospective study, we reported the clinical outcome of nonmetastatic breast cancer patients according to CTC detection.

Patients and methods: In 115 nonmetastatic patients diagnosed with large operable or locally advanced breast cancer, we prospectively detected CTC using the CellSearch system before and after neoadjuvant chemotherapy in a phase II trial (REMAGUS02).

Results: At baseline, 23% of patients were CTC positive, but only 10% had >1 CTC/7.5 ml of blood. After a median follow-up of 36 months, CTC detection before chemotherapy was an independent prognostic factor for both distant metastasis-free survival [DMFS; P = 0.01, relative risk (RR) = 5.0, 95% confidence interval (CI) 1.4-17] and overall survival (OS; P = 0.007, RR = 9, 95% CI 1.8-45). CTC detection after chemotherapy was of less significance (P = 0.07 and 0.09, respectively). Moreover, CTC detection showed interesting characteristics as an individual predictive test for metastatic relapses (sensibility 55%, specificity 81%, and global accuracy 77%).

Conclusions: Detection of > or =1 CTC/7.5 ml before neoadjuvant chemotherapy can accurately predict OS. Our findings may change the clinical management of nonmetastatic breast cancer and indicate that the metastatic efficiency of CTC could be higher than previously reported.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology*
  • Carcinoma / diagnosis
  • Carcinoma / drug therapy
  • Carcinoma / mortality*
  • Carcinoma / pathology*
  • Celecoxib
  • Cell Separation
  • Cyclophosphamide / administration & dosage
  • Docetaxel
  • Early Detection of Cancer / methods*
  • Epirubicin / administration & dosage
  • Female
  • Humans
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Metastasis
  • Neoplastic Cells, Circulating / pathology*
  • Pyrazoles / administration & dosage
  • Sulfonamides / administration & dosage
  • Survival Analysis
  • Taxoids / administration & dosage
  • Time Factors
  • Trastuzumab
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Pyrazoles
  • Sulfonamides
  • Taxoids
  • Docetaxel
  • Epirubicin
  • Cyclophosphamide
  • Celecoxib
  • Trastuzumab

Associated data

  • ISRCTN/ISRCTN10059974