Evaluation of Radiation Dose-Response in a Breast Cancer Brain Metastasis Model

Abstract

The second incidence of brain metastases is from breast cancer. Radiotherapy, a standard treatment for brain metastasis, limits cancer division by inducing DNA double-stranded breaks (DSBs). Currently, identical radiation doses are prescribed for all types of brain metastases but little is known about their histological responses. In this thesis, we initiated a radiation dose-response study in a triple-negative human breast cancer brain metastasis mouse model using a custom designed 3D-printed restrainer to assist half-brain irradiation. We quantified the amount of DSBs in tumors and mouse brain tissues using γ-H2AX marker at 30 minutes (acute) and 11 days (longitudinal) after treatment with doses of 8-24 Gy. We also evaluated tumors’ response using histology and MRI. In the longitudinal study we found significant differences in the amount of DSBs, tumor cell density, and nucleus size between irradiated surviving and non-irradiated tumors. These results gave insights to brain metastasis response after radiotherapy

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