On the hunt for genetic clues to breast cancers that spread to the brain

UNC Lineberger researcher Carey Anders, MD, wants to understand why some breast cancers metastasize to the brain, and what drives them. She recently was awarded a three-year, $450,000 grant to study genetic features of breast cancer brain metastases to try to answer those questions.

On the hunt for genetic clues to breast cancers that spread to the brain click to enlarge Carey Anders, MD, is trying to uncover the genetic links to spur some breast cancers to spread to the brain

Carey Anders, MD, is looking for the Achilles’ heel of breast cancer that has spread to the brain.

Anders is leading research at the University of North Carolina Lineberger Comprehensive Cancer Center to try to identify the biological reason behind why some breast cancers metastasize to the brain. She recently was awarded a 2016 Conquer Cancer Foundation/Breast Cancer Research Foundation Advanced Clinical Research Award in Breast Cancer -- a three-year, $450,000 grant award -- to support her work.

By understanding the biological underpinning of the disease’s spread, Anders hopes to be able to find more effective targeted treatments for this disease.

“We want to understand why brain metastases occur, and to understand once they get there, what drives them,” said Anders, a UNC Lineberger member and associate professor in the UNC School of Medicine. “If we can identify the Achilles’ heel of these tumors, then we can attack them with a drug that hits the right target to halt the cancer’s progression, but also, potentially, prevent these cells from getting to the brain all together.”

Anders is on a mission to fight breast cancer brain metastasis both in the lab and in the clinic. About four years ago, frustrated by a lack of options for new treatments for breast cancer patients with brain metastasis, she helped start the brain metastases clinic at the N.C. Cancer Hospital.

Many patients with brain metastases historically have been excluded from clinical trials because of limited expectations for their survival, as well as the challenges of overcoming the blood-brain barrier, a natural filtration system for the brain that has been thought to prevent treatments from reaching metastases.

The UNC Brain Metastases Specialty Clinic launched in 2012 to coordinate patients’ surgical, radiation and drug treatments, and to conduct clinical research aimed at developing new treatments. Anders co-directs the clinic with Matthew Ewend, MD, co-director of UNC Lineberger’s neuro-oncology program and chair in the Department of Neurosurgery at UNC School of Medicine, and Timothy Zagar, MD, UNC Lineberger member and co-director of the UNC CyberKnife Radiosurgery Program.

“Seeing breast cancer patients in my clinic, and recognizing how functional many of them were despite their brain metastases, but not being able to offer them a clinical trial, was very frustrating to me,” Anders said. “I saw that it was an unmet medical need.”

Anders and the other physicians at the clinic have treated 65 patients with breast cancer brain metastases between January of 2012 and January of 2015. Thirty-two percent of those patients were enrolled in clinical trials through the clinic.

Until recently, survival rates had been between two and 16 months for breast cancer patients with brain metastases, but Anders reported in a recent paper in The Oncologist that these patients are doing better, with survival rates improving to 14-24 months.

Median survival from diagnosis for all patients was about two years. For human epidermal growth factor receptor 2-positive (HER2) breast cancer, median survival was about three years. For patients with triple negative breast cancer – a particularly aggressive type of breast cancer that lacks targeted treatment options – survival was about 1.15 years.

“We were really surprised to see how well many of these patients were doing, especially the HER2-positive population, with many of those patients living out the three-year mark with brain metastases,” Anders said. “That was really remarkable.”

In addition to her clinical responsibilities, Anders conducts pre-clinical research. In her lab at UNC Lineberger, she has led studies aimed at identifying treatments or combinations of therapies that cross the blood-brain barrier and are effective against triple negative breast cancer that has metastasized to the brain.

Her new project will include both triple negative and HER2-positive breast cancer, two subtypes that more commonly spread to the brain. The research will include running genetic tests to try to identify common DNA changes and gene expression patterns that could be driving breast cancer to spread to the brain. Anders and her colleagues, including Benjamin Vincent, MD, a clinical oncology fellow in the UNC School of Medicine Division of Hematology/Oncology, also plan to analyze the immune system cells in and around the tumors to understand the role the body’s natural defense system is playing in cancer’s spread to the brain, and in patient’s survival outcomes.

“Our main goals are to understand why brain metastases occur, and once they get there, what drives them,” Anders said. “The hope would be to design therapeutic interventions for both of those scenarios.”

In addition to Anders, other authors on the article published in The Oncologist were Megan J. McKee, Kevin Keith, Allison M. Deal, Amy L. Garrett, Amy A. Wheless, Rebecca L. Green, Julie M. Benbow, E. Claire Dees, Lisa A. Carey, Matthew G. Ewend, and Timothy M. Zagar.

Research described in the paper was supported by the National Cancer Institute. Individual authors were funded by the Damon Runyon Cancer Research Foundation, the Breast SPORE Career Development funding, and the Komen Foundation.