Evaluation of the Immunological Effects of a Combined Treatment With Radiation and Cyclophosphamide in Metastasized Breast Cancer Patients

In metastasized of locally advanced breast cancer patients, local problems often occur like skin metastases, ulcerations or lymph node metastases. These problems are related to a worse quality of life, while overall survival is generally in the order of months to years. Treatment of these lesions is challenging, especially after failure of first or second line systemic therapy. Local treatments, like radiation, are able to give short-term palliation, but the effect is often disappointing in the long run. Therefore, the search for new therapeutic strategies like the combination of local and systemic treatments is emerging. Recent investigations clearly show that radiation is capable of inducing a systemic anti-tumor response. Both in mouse models and in patients, it was reported that irradiating one metastasis can slow down the growth of other non-irradiated metastases. This effect is called the "abscopal effect" and is immune-mediated. There are also several chemotherapeutics that are capable of influencing the immune response like cyclophosphamide. Cyclophosphamide is a known inducer of immunogenic cell death, which leads to the activation of dendritic cells and thus the presentation of antigens. In this pilot study the investigators wish to identify the immunological effects of combined treatment with radiation and cyclophosphamide in breast cancer patients. Five patients with metastasized breast carcinoma will be treated with the combined treatment and the immunological effects will be monitored using repeat blood draws and biopsies. These effects will be correlated to the clinical response.