No abstract

#4057 Background: Recombinant human granulocyte-colony stimulating factor (rhG-CSF) is commonly given to breast cancer patients to prevent neutropenia during chemotherapy. It binds to the G-CSF receptor (G-CSFR) on neutrophil precursors, promoting their proliferation within the bone marrow. We observed breast cancer growth in patients with advanced breast cancer during rhG-CSF administration. The G-CSFR is present on some solid tumors, but has not been examined in breast cancer. We asked whether breast cancer cells express the G-CSFR, and whether rhG-CSF has any direct effects on breast cancer proliferation or invasion in vitro.
 Material and Methods: MDA MB231 is a highly aggressive ER–PR–Her2/neu– breast cancer cell line derived from a human pleural effusion. We analyzed this cell line for the presence of the G-CSFR by immunohistochemistry, reverse-transcriptase PCR (RT-PCR), Western Blot analysis and flow cytometry. We sequenced DNA products of RT-PCR to verify results. We examined the effects of physiologic doses of rhG-CSF on breast cancer cell proliferation and invasion using MTT proliferation and Matrigel transwell assays, respectively.
 Results: MDA MB231 breast cancer cells express G-CSFR protein and mRNA. Of seven known G-CSFR isoforms, we found evidence of isoforms 1 and 4. Treating MDA MB231 breast cancer cells with rhG-CSF at 50ng/ml did not increase cell proliferation, but did increase invasion across a Matrigel-coated transwell membrane. Cells treated with rhG-CSF appeared more stellate than untreated cells. Studies are ongoing to evaluate which signal transduction pathways and genes are involved in this increased invasion response. The effects of rhG-CSF on breast cancer growth in vivo are also being examined in murine models.
 Discussion: rhG-CSF is given routinely as part of many adjuvant chemotherapy regimens for breast cancer. Although dose-dense regimens using rhG-CSF have shown equivalent or improved survival when compared to standard dosing regimens, it is possible that rhG-CSF may increase the growth or invasive potential of some breast cancers. It is also possible that rhG-CSF could mobilize breast cancer cells from the bone marrow, making these cells more susceptible to chemotherapy. These possibilities should promote thoughful use of rhG-CSF in the clinical setting, and should factor into the design and implementation of clinical trials using rhG-CSF. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4057.

No abstract