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

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Abstract

Earlier results [1], suggesting an autocrine tumor cell stimulation by CSF-1, are in agreement with data by Fildermannet al. [2], 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 [3]. Down-regulation of monocyte class II antigen expression after exposure to high concentrations of CSF-1 [4] 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-immuno-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.

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Authors and Affiliations

  1. Département de Médecine Oncologique, Institut Curie, 26 rue d'Ulm, 75231, Paris Cedex 05, France

    Susy M. Scholl & Pierre Pouillart

  2. Laboratoire d'Oncogénétique, Centre René Huguenin, 32 rue Dailly, 92211, St. Cloud, France

    Rosette Lidereau

  3. Département de Radiothérapie, Institut Curie, 26 rue d'Ulm, 75321, Paris, France

    Anne de la Rochefordière

  4. Département de Radiothérapie, Centre René Huguenin, 32 rue Dailly, 92211, St. Cloud, France

    Christine Cohen-Solal Le-Nir

  5. Département de Biostatistiques, Institut Curie, 26 rue d'Ulm, 75321, Paris, France

    Véronique Mosseri

  6. Département de Statistiques, Centre René Huguenin, 32 rue Dailly, 92211, St. Dailly, France

    Catherine Noguès

  7. Départment of Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, 10461, Bronx, New York, USA

    E. Richard Stanley

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Scholl, S.M., Lidereau, R., de la Rochefordière, A. et al. Circulating levels of the macrophage colony stimulating factor CSF-1 in primary and metastatic breast cancer patients. A pilot study. Breast Cancer Res Tr 39, 275–283 (1996). https://doi.org/10.1007/BF01806155

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