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ECC 2015: Genetic Screening of Brain Metastases Could Reveal New Targets for Treatment

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Key Points

  • In 56% of patients, genetic alterations that potentially could be targeted with drugs were found in the brain metastasis but not in the primary tumor.
  • If a patient had more than one brain metastasis, each was genetically similar.
  • Researchers concluded that brain metastases and the primary tumor share a common genetic ancestor. Once a cancer cell has moved from the primary site to the brain, it continues to develop and amass genetic mutations.

Unraveling the genetic sequences of cancer that has spread to the brain could offer unexpected targets for effective treatment, according to new research (Abstract 2905) presented at the 2015 European Cancer Congress in Vienna, Austria, and published simultaneously by Brastianos et al in Cancer Discovery.

Researchers explained they found that the primary cancer in a patient’s body might have important differences at a genetic level from brain metastases. This insight could suggest new lines of treatment.

Priscilla Brastianos, MD, a neuro-oncologist and Director of the Brain Metastasis Program at Massachusetts General Hospital, said, “Brain metastases are a devastating complication of cancer. Approximately 8%–10% percent of cancer patients will develop brain metastases, and treatment options are limited. Even where treatment is successfully controlling cancer elsewhere in the body, brain metastases often grow rapidly.”

Study Details

Dr. Brastianos and her colleagues studied tissue samples from 104 adults with cancer. In collaboration with Scott Carter, PhD, and Gad Getz, PhD, at the Broad Institute, they analyzed the genetics of biopsies taken from the primary tumor, brain metastases, and normal tissues in each adult. For 20 patients, they also had access to metastases elsewhere in the body.

The researchers found that, in every patient, the brain metastasis and primary tumor shared some of their genetics, but there were also key differences. In 56% of patients, genetic alterations that potentially could be targeted with drugs were found in the brain metastasis but not in the primary tumor.

“We found genetic alterations in brain metastases that could affect treatment decisions in more than half of the patients in our study,” Dr. Brastianos said. “We could not detect these genetic alterations in the biopsy of the primary tumor. This means that when we rely on analysis of a primary tumor, we may miss mutations in the brain metastases that we could potentially target and treat effectively with drugs.”

This study also found that if a patient had more than one brain metastasis, each was genetically similar.

To date, scientists have had limited understanding of how cancers change genetically as they spread from the primary tumor. The researchers used their findings to map the evolution of a cancer through a patient’s body and draw up a so-called phylogenetic tree for each patient to demonstrate how the cancer had spread and where each metastasis had come from.

They concluded that brain metastases and the primary tumor share a common genetic ancestor. Once a cancer cell (clone) has moved from the primary site to the brain, it continues to develop and amass genetic mutations. The genetic similarity of the brain metastases in individual patients suggests that each brain metastasis has developed from a single clone entering the brain.

The genetic changes in brain metastases are independent of any occurring in the primary tumor and in metastases elsewhere in the body, the researchers said.

More Therapeutic Options

Characterization of the genetics of a patient’s primary cancer can be used to optimize treatment decisions, so that drugs that target specific mutations in the cancer can be chosen. However, brain metastases are not routinely biopsied and analyzed.

Dr. Brastianos said, “When brain metastasis tissue is available as part of clinical care, we are suggesting sequencing and analysis of that sample. It may offer more therapeutic opportunities for the patient. Genetic characterization of even a single brain metastasis may be superior to that of the primary tumor or a lymph node biopsy for selection of a targeted treatment.”

The need for new approaches to treating brain metastases is urgent, she said. “Brain metastases represent an unmet need in current cancer care. More than half of the patients diagnosed with brain metastasis will die within a few months.”

Dr. Brastianos concluded by saying more research is needed. “The clinical relevance of this finding needs to be studied more in prospective clinical trials. We still need to determine whether targeting the genetic mutations in the brain will lead to improved clinical outcomes.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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