Breast Cancer Research and Treatment

, Volume 137, Issue 2, pp 503–510

The prognostic impact of circulating tumor cells in subtypes of metastatic breast cancer

Authors

  • Markus Wallwiener
    • Department of Obstetrics and GynecologyUniversity of Heidelberg
    • National Center for Tumor DiseasesUniversity of Heidelberg
    • Department of Obstetrics and GynecologyUniversity of Tübingen
  • Irène Baccelli
    • HI-STEM, German Cancer Research Center (DKFZ)
  • Sabine Riethdorf
    • Department of Tumour BiologyUniversity Medical Center Hamburg-Eppendorf
  • Sarah Schott
    • Department of Obstetrics and GynecologyUniversity of Heidelberg
    • National Center for Tumor DiseasesUniversity of Heidelberg
  • Klaus Pantel
    • Department of Tumour BiologyUniversity Medical Center Hamburg-Eppendorf
  • Frederik Marmé
    • Department of Obstetrics and GynecologyUniversity of Heidelberg
    • National Center for Tumor DiseasesUniversity of Heidelberg
  • Christof Sohn
    • Department of Obstetrics and GynecologyUniversity of Heidelberg
  • Andreas Trumpp
    • HI-STEM, German Cancer Research Center (DKFZ)
  • Brigitte Rack
    • Department of Obstetrics and GynecologyCampus Innenstadt, Ludwig Maximilian University of Munich
  • Bahriye Aktas
    • Department of Obstetrics and GynecologyUniversity of Essen
  • Erich-Franz Solomayer
    • Department of Obstetrics and GynecologySaarland University Medical Center
  • Volkmar Müller
    • Department of GynecologyUniversity of Hamburg-Eppendorf
  • Wolfgang Janni
    • Department of Obstetrics and GynecologyUniversity of Ulm
  • Andreas Schneeweiss
    • Department of Obstetrics and GynecologyUniversity of Heidelberg
    • National Center for Tumor DiseasesUniversity of Heidelberg
  • Tanja Natascha Fehm
    • Department of Obstetrics and GynecologyUniversity of Tübingen
Clinical trial

DOI: 10.1007/s10549-012-2382-0

Cite this article as:
Wallwiener, M., Hartkopf, A.D., Baccelli, I. et al. Breast Cancer Res Treat (2013) 137: 503. doi:10.1007/s10549-012-2382-0

Abstract

The detection of circulating tumor cells (CTCs) in the peripheral blood of metastatic breast cancer (MBC) patients is an independent marker of prognosis. This large prospective multicenter study aimed to assess the impact of CTCs on overall survival (OS) and progression free survival (PFS) in patients with predefined molecular subgroups of MBC. To this end, 468 MBC patients were divided into three subgroups based on immunohistochemical staining of the primary tumor: (1) hormone receptor-positive/HER2-negative (HorR+/HER2−), (2) HER2-positive (HER2+), and (3) HorR-negative/HER2-negative (HorR−/HER2−) patients. CTC status (<5 CTCs/7.5 ml blood (CTC-negative) vs. ≥5 CTCs/7.5 ml blood (CTC-positive)) was determined using the CellCearch® system before patients started a new line of therapy. At baseline, 205 (42 %) patients were CTC-positive. On multivariate analysis, CTC-positivity was an independent prognostic factor for shorter PFS and OS. In HorR+/HER2− patients, median PFS [95 % CI] of CTC-negative versus CTC-positive patients was 8.60 [5.93–11.27] versus 4.33 [3.29–5.38] months (p < 0.001), in HER2+ patients 7.60 [5.40–9.79] versus 6.60 [4.20–9.00] months (p = 0.477) and in HorR−/HER2− patients 5.83 [5.09–6.78] versus 3.05 [1.81–4.29] months (p < 0.001), respectively. Median OS [95 % CI] of CTC-negative versus CTC-positive patients was as follows: not reached by either in the HorR+/HER2− subgroup (p < 0.001), not reached versus 18.07 [11.10–25.05] months (p = 0.001) in the HER2+ subgroup, and not reached versus 8.57 [4.07–13.07] months in the HorR−/HER2− subgroup (p = 0.001). In conclusion, our results strongly confirm the independent prognostic value of CTC enumeration in MBC patients. In contrast to recent reports, there was no association between primary tumor-based molecular subgroups and the impact of CTC status on OS. Hence, CTC status may help to identify patients who require aggressive therapy, especially among those with triple-negative MBC.

Keywords

Metastatic breast cancer Circulating tumor cells Progression free survival Overall survival Molecular subtypes Prognosis

Abbreviations

CI

Confidence interval

CTC(s)

Circulating tumor cell(s)

CTC−

CTC-negative

CTC+

CTC-positive

EpCam

Epithelial cell adhesion molecule

ER

Estrogen receptor

FDA

Food and drug administration (USA)

HER2

Human epidermal growth factor receptor 2

HorR

Hormone receptor

MBC

Metastatic breast cancer

OS

Overall survival

PFS

Progression free survival

PgR

Progesterone receptor

RECIST

Response evaluation criteria in solid tumors

Copyright information

© Springer Science+Business Media New York 2012