Racing Against the Clock: The Life and Science of Priscilla K. Brastianos, MD

Kate Johnson


August 16, 2016

Editor's Note:
The future of cancer research lies in the hands of an emerging generation of young oncologists. Medscape Oncology's Young Investigator series profiles oncologists who, through microscopes and clinical trials, are pursuing answers that could unlock new strategies in the treatment and prevention of cancer. The first profile is of Priscilla K. Brastianos, MD, director of the Central Nervous System Metastasis Program at Massachusetts General Hospital, who studies genomic drivers of brain metastasis in breast cancer patients with an urgency that is deeply personal.

The Changing Face of Metastatic Cancer

In the fall of 2014, along Boston's Esplanade, you might have noticed a grieving woman throwing flowers into the Charles River.

Sometimes she came twice a day, white petals in the current, a silent communion with her mother and grandmother, both of them taken too soon by breast cancer that metastasized to the brain.

Hurrying back to the lab, Priscilla Brastianos, MD, would refocus: dissecting DNA and performing whole-exome sequencing on craniotomy samples from cancer patients—some of them not yet 40 at diagnosis, almost all of them now deceased.

For Dr Brastianos, this is more than simply honoring those who came before her; she has made it her life's goal to crack the riddle that's made metastases so challenging to treat.

"I want to change the face of metastatic cancer, because 90% of cancer patients die of metastatic disease," she said in a recent interview with Medscape.

"There are 200,000-300,000 cases of metastatic brain cancer in the United States per year. They might be stable everywhere else, but when they progress in the brain, about one half of them die from that progression. My entire career is going to be focused on understanding what the molecular drivers are, and then the new drug targets."

Within months of her mother's death, Dr Brastianos and her colleagues at Harvard Medical School had published the largest study to date comparing genetic drivers in brain metastases with those in the original primary tumor.[1]

Priscilla Brastianos, MD, in 2013, discusses the intentions of her brain metastasis study.
Courtesy of Susan G. Komen

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The findings strengthen the notion that brain metastases present new opportunities for targeted therapies beyond those that are used when a patient is first diagnosed.

"In all cancer samples, we observed branched evolution, in that all metastatic and primary sites shared a common ancestor yet continued to evolve independently," she said over lunch at her desk on the third-floor office of the Simches Research Center. "In 53% of cases, we found clinically actionable alterations in the brain metastases that are not detectable in the matched clinically sampled primary tumor."

We found clinically actionable alterations in the brain metastases that are not detectable in the matched clinically sampled primary tumor.

Fueled by this discovery, she and her colleagues at the Priscilla K. Brastianos Lab are now planning a genomically driven brain metastases trial—the first of its kind in the United States.

"Before my mom died, she told me and my brother that she wanted us to find better therapies so that people aren't dying of metastatic breast cancer. We promised her we would," said Dr Brastianos, a Canadian, who just 10 years out of Johns Hopkins University School of Medicine has fast-tracked toward fulfilling her mother's wish.

The brain metastasis study is starting with a pilot investigation looking at cyclin-dependent kinase inhibitors, because the majority of mutations they found are potentially sensitive to these drugs.

"If this is feasible, then we'll expand to do more cohorts," she said.

Mutations affecting the PI3K/AKT/mTOR pathway were also common, as well as mutations that are potentially sensitive to HER2/EGFR inhibitors, such as trastuzumab, gefitinib, cetuximab, erlotinib, or lapatinib.

"We were lucky enough to find mutations for which there are already agents in the clinic, or under investigation. So we will investigate to see whether they have activity in the brain—first in the lab, but also in clinical trials."


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