Prognostic relevance of the HER2 status of circulating tumor cells in metastatic breast cancer patients screened for participation in the DETECT study program

Research output: Contribution to journalResearch articleContributedpeer-review


  • DETECT Study Group - (Author)
  • Department of Gynecology and Obstetrics
  • University of Hamburg
  • Universitätsklinikum Schleswig-Holstein - Campus Lübeck
  • Ulm University
  • Friedrich-Alexander University Erlangen-Nürnberg
  • German Cancer Research Center (DKFZ)
  • University of Tübingen
  • University Hospital Duesseldorf
  • University of Duisburg-Essen
  • Onkologie UnterEms
  • Ludwig Maximilian University of Munich


Background: Circulating tumor cells (CTCs) have been reported to predict clinical outcome in metastatic breast cancer (MBC). Biology of CTCs may differ from that of the primary tumor and HER2-positive CTCs are found in some patients with HER2-negative tumors. Patients and methods: Patients with HER2-negative MBC were screened for participation in DETECT III and IV trials before the initiation of a new line of therapy. Blood samples were analyzed using CELLSEARCH. CTCs were labeled with an anti-HER2 antibody and classified according to staining intensity (negative, weak, moderate, or strong staining). Results: Screening blood samples were analyzed in 1933 patients with HER2-negative MBC. As many as 1217 out of the 1933 screened patients (63.0%) had ≥1 CTC per 7.5 ml blood; ≥5 CTCs were detected in 735 patients (38.0%; range 1-35 078 CTCs, median 8 CTCs). HER2 status of CTCs was assessed in 1159 CTC-positive patients; ≥1 CTC with strong HER2 staining was found in 174 (15.0%) patients. The proportion of CTCs with strong HER2 staining among all CTCs of an individual patient ranged between 0.06% and 100% (mean 15.8%). Patients with estrogen receptor (ER)- and progesterone receptor (PR)-positive tumors were more likely to harbor ≥1 CTC with strong HER2 staining. CTC status was significantly associated with overall survival (OS). Detection of ≥1 CTC with strong HER2 staining was associated with shorter OS [9.7 (7.1-12.3) versus 16.5 (14.9-18.1) months in patients with CTCs with negative-to-moderate HER2 staining only, P = 0.013]. In multivariate analysis, age, ER status, PR status, Eastern Cooperative Oncology Group performance status, therapy line, and CTC status independently predicted OS. Conclusion: CTC detection in patients with HER2-negative disease is a strong prognostic factor. Presence of ≥1 CTC with strong HER2 staining was associated with shorter OS, supporting a biological role of HER2 expression on CTCs.


Original languageEnglish
Article number100299
Pages (from-to)1-8
Number of pages8
JournalESMO open
Issue number6
Publication statusPublished - Dec 2021

External IDs

PubMed 34839105


Sustainable Development Goals

ASJC Scopus subject areas


  • breast cancer, circulating tumor cell, HER2 status, liquid biopsy, survival

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