Circulating levels of the macrophage colony stimulating factor CSF-1 in primary and metastatic breast cancer patients. A pilot study

Susy M. Scholl, Rosette Lidereau, Anne De La Rochefordière, Christine Cohen Solal Le-Nir, Véronique Mosseri, Catherine Noguès, Pierre Pouillart, E. Richard Stanley

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Earlier results, suggesting an autocrine tumor cell stimulation by CSF-1, are in agreement with data by Fildermann et al., showing an enhanced motility and invasiveness in the CSF-1 receptor expressing BT20 breast cancer cell line upon stimulation with recombinant CSF-1. Tumor-cell secreted CSF-1 has also been shown to cause monocyte recruitment, but not cytotoxicity. Down-regulation of monocyte class II antigen expression after exposure to high concentrations of CSF-1 may decrease macrophage-mediated tumor cytotoxicity and favor tolerance. Raised CSF-1 serum levels may thus increase tumor metastatic behavior as well as cause immune suppression in advanced stage disease. We set out to evaluate serum CSF-1 levels in primary and metastatic breast cancer. Serum samples from one hundred and eighteen primary breast cancer patients and seventy-five patients with metastatic disease were assayed by radio-immune-assay (RIA) for circulating colony-stimulating factor 1. Mean serum levels were significantly higher in the metastatic population (9.7 ng/ml ± 0.8) as compared to the patients with primary tumors (4.2 ± 0.2) (p = 0.0001). Patients with early stage tumors (T0/T1/T2) had significantly lower levels than patients with tumors of larger size (T3/T4) (p = 0.0001). Relapse and survival statistics were analyzed using Kaplan-Meier estimates. Samples from 118 primary breast cancer patients were available to study. The median follow up was 85 months (range: 1-108). An elevated CSF-1 concentration (> 6.6 ng/ml or > 550 Units/ml) was associated with a shorter disease free interval (p = 0.03). In a multivariate analysis, including T (clinical tumor size), N (clinical node status), histological grade, and hormone receptor status, CSF-1 remained significantly associated with a poorer outcome (relative risk of relapse: RR: 3.3 [1.3-8.5]), together with tumor size (RR: 2.8 [1-8.2]) and clinically involved nodes (RR: 4.1 [2.1-8]). These results were not modified following adjustment for type of treatment. We conclude that raised circulating CSF-1 levels may be an indicator of early metastatic relapse.

Original languageEnglish (US)
Pages (from-to)275-283
Number of pages9
JournalBreast Cancer Research and Treatment
Volume39
Issue number3
DOIs
StatePublished - 1996

Keywords

  • Breast cancer
  • CSF-1
  • Cytokines
  • Metastasis
  • Prognosis
  • Serum markers

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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