Clinical trial

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

  • Markus WallwienerAffiliated withDepartment of Obstetrics and Gynecology, University of HeidelbergNational Center for Tumor Diseases, University of Heidelberg
  • , Andreas Daniel HartkopfAffiliated withDepartment of Obstetrics and Gynecology, University of Tübingen Email author 
  • , Irène BaccelliAffiliated withHI-STEM, German Cancer Research Center (DKFZ)
  • , Sabine RiethdorfAffiliated withDepartment of Tumour Biology, University Medical Center Hamburg-Eppendorf
  • , Sarah SchottAffiliated withDepartment of Obstetrics and Gynecology, University of HeidelbergNational Center for Tumor Diseases, University of Heidelberg
  • , Klaus PantelAffiliated withDepartment of Tumour Biology, University Medical Center Hamburg-Eppendorf
  • , Frederik MarméAffiliated withDepartment of Obstetrics and Gynecology, University of HeidelbergNational Center for Tumor Diseases, University of Heidelberg
  • , Christof SohnAffiliated withDepartment of Obstetrics and Gynecology, University of Heidelberg
  • , Andreas TrumppAffiliated withHI-STEM, German Cancer Research Center (DKFZ)
    • , Brigitte RackAffiliated withDepartment of Obstetrics and Gynecology, Campus Innenstadt, Ludwig Maximilian University of Munich
    • , Bahriye AktasAffiliated withDepartment of Obstetrics and Gynecology, University of Essen
    • , Erich-Franz SolomayerAffiliated withDepartment of Obstetrics and Gynecology, Saarland University Medical Center
    • , Volkmar MüllerAffiliated withDepartment of Gynecology, University of Hamburg-Eppendorf
    • , Wolfgang JanniAffiliated withDepartment of Obstetrics and Gynecology, University of HeidelbergDepartment of Obstetrics and Gynecology, University of Ulm
    • , Andreas SchneeweissAffiliated withDepartment of Obstetrics and Gynecology, University of HeidelbergNational Center for Tumor Diseases, University of Heidelberg
    • , Tanja Natascha FehmAffiliated withDepartment of Obstetrics and Gynecology, University of Tübingen

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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