Breast cancer aggressiveness in young patients

Division Of Basic Sciences - Nci

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Abstract

Lung metastasis in four experimental model systems was not affected by mouse age, and liver metastases were unaffected in one model system. In four brain metastasis model systems, young mice developed significantly greater metastases. We hypothesized that the host immune system contributes to the increased incidence of brain metastases in young hosts. Immune profiling of metastatic and naive old and young mice demonstrated a paucity of microglia in young mice. Experiments have been conducted using CSF-1R inhibitors, which is a viability signal for microglia. CSF-1R inhibition attenuated the development of brain metastatasis preferentially in young animals. Current work is examining clinical candidate CSF-1R inhibitors in prevention and treatment settings. To identify additional alterations in brain metastases in young patients, we conducted a proteomic screen of a hematogenous model system, to laser capture dissect metastasis, the metastatic microenvironment, and uninvolved brain. Profound changes to the metastatic microenvironment were identified with mouse age and are being further characterized.