Identifying Drivers of Brain Metastases

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Brain metastasis is a common complication in breast cancer and occurs in up to 30% of patients with metastatic breast cancer. With advances in diagnostic techniques and improved treatments, the incidence of this devasting complication is increasing. Of patients with clinically significant brain metastases, the majority die within months. Unfortunately, clinical trials commonly exclude patients with brain metastases. An understanding of the molecular mechanisms of brain metastasis and better treatment approaches are urgently needed.

Cancer arises primarily from the acquisition of alterations in the DNA of cells. Knowledge of these genetic alterations has lead to the identification of new groundbreaking targeted therapies for cancer. Among these are trastuzumab, which targets Her2/neu in HER2+ breast cancer, imatinib which targets bcr-abl in chronic myelogenous leukemia, and PLX4032 which targets BRAF in melanoma. These treatments not only induce significant responses but are much less toxic than traditional chemotherapy. To identify mutations such as these, international efforts to sequence the genomes of many types of cancers are underway. However, most of these efforts do not include metastatic disease despite the devastating clinical impact of this disease.

This study aims to detect the changes in the DNA of metastatic brain tumors in breast cancer. Dr. Brastianos and her team hypothesize that tumors undergo multiple genetic changes that are responsible for brain metastases. Metastasis is a complex multi-step process and these studies will identify mutations responsible for each of these steps. The team will utilize state-of-the-art sequencing technologies at the Broad Institute and the Dana-Farber Cancer Institute to characterize the genomics of brain metastases from breast cancer. The comprehensive identification of somatic genetic events in brain metastases from breast cancer has the potential to transform our understanding of this disease, and will bring us closer to developing targeted approaches to metastatic disease of the brain from breast cancer.