When Robert Breeze, MD, started medical school at the University of California San Diego in 1977, brain metastases from melanoma were considered a terminal diagnosis. Surgery to remove brain metastases was rare since the standard of care was strictly palliative.
“At that time, treatment of cancer relied heavily on chemotherapy, and most of those agents did not cross the blood-brain barrier,” Breeze says. “Once cancer went to the brain, there was a strong likelihood of death within six weeks to six months since brain metastases progress rapidly without treatment.”
Today, specialists in medical oncology, radiation oncology, and neurosurgery work closely to aggressively treat brain metastases from melanoma and other cancers — a level of collaboration that was uncommon at the start of Breeze's career. In the 1980s, Breeze attended the University of Southern California for residency training. It was there he performed his first brain metastasis surgery on a patient experiencing frequent seizures.
“The surgery relieved the patient’s seizures,” Breeze says. “This made their last six months better for them.”
Despite the optimal outcome and consent from the patient, Breeze recalls that surgical decision was considered controversial at the time.
“The general consensus among people outside of neurosurgery was that brain surgery required a long recovery and would cut into a patient's life span,” Breeze says. “But the techniques for brain metastases were evolving and recoveries could be much shorter than expected.”
In the 1950s and 1960s, stereotactic neurosurgery was used exclusively to treat movement disorders and relied on brain atlas coordinates to target the ablative surgery. The invention of the CT scanner revived stereotactic surgery.
Breeze recalls reading about the invention of the CT scanner when he was in high school. By the time he started his residency training, the technology was available in most major U.S. hospitals. In the 1980s, image-guided stereotactic neurosurgery using CT scans was introduced.
At USC, Breeze was part of a team that tested one of the two original prototypes of the first dedicated image-guided stereotactic frame. During residency, he was put in charge of the frame and quickly mastered stereotactic biopsies.
“It was a new generation of stereotactic neurosurgery," Breeze says. "We could now accurately target lesions deep in the brain for both biopsy and, at times, resection."
Soon after Breeze arrived at the University of Colorado in 1987, he met Bill Robinson, MD, PhD, a medical oncologist with an academic interest in melanoma. The two combined their expertise and began treating patients with brain metastases from melanoma.
“Dr. Robinson wanted me to operate on melanoma metastases,” Breeze says. “That’s how I got interested in melanoma.”
Because their approach was not yet considered the standard of care, Breeze says he and Robinson faced criticism that their surgical treatment was too aggressive.
Breeze persevered and refined his surgical skills to treat patients with brain metastases from melanoma who may have died sooner without his care. Slowly, perceptions of stereotactic surgery in these cases began to change as technology advanced and the surgery and treatments became more effective.
In 1993, a Gamma Knife® machine was installed in Colorado — among the first in the country — and because Breeze had extensive stereotactic experience, he was asked to use it.
The machine is a noninvasive stereotactic radiosurgery device primarily used to treat brain tumors and other neurological conditions by delivering a single shot of high dose radiation to a precise location in the brain to shrink or eliminate a tumor. The new technology helped minimize harm to the surrounding tissue and exposes the body to less radiation than conventional radiation treatments.
“I had to get special permission from the dean at the time to operate at this site,” Breeze says. “I had the option with every brain metastasis I saw to either take it out or decide if it was best treated by radiosurgery.”
Today, medical centers across the country with a high volume of melanoma cases routinely offer multidisciplinary treatment of melanoma brain metastases.
“Now, oncologists are actively treating brain metastases and actively engaging me,” Breeze says. “To have this kind of interaction where an oncologist asks me to take something out would have been unimaginable in residency.”
Brain metastases from melanoma often can go undetected for up to a year.
In the past, when brain metastases appeared on a scan, oncologists would stop the systemic therapy that kept the cancer in the rest of the body at bay. In those cases, they presumed that treatment was no longer effective.
Breeze explains that in many cases, brain metastases are likely present when the cancer begins to metastasize to other parts of the body, like the lungs, but are too small to be detected by medical imaging.
“Every time I treat someone with eight brain metastases, they might actually have 10,” Breeze says. “I scan them every four to eight weeks for up to a year or more, and then every six months.”
In the past, neurosurgeons focused on treating the brain while medical oncologists and radiation oncologists focused on treating the rest of the body. Today, treatments are far more integrated.
“Brain metastases always defined when the disease was fatal, but now many drugs penetrate the brain and it is a joint effort between neurosurgery, medical oncology, and radiation oncology,” Breeze says. “This has resulted in the brain metastases not always being the limiting factor in the overall survival of cancer patients."
Early in his career, surgically treating three brain metastases was unheard of. Today, Breeze says treating patients with many brain metastases is common. The most he has treated in a single patient is 101.
Academic medical centers, such as CU Anschutz, provide the most optimal care possible for patients with brain metastases. There currently are more than 50 melanoma clinical trials offered at the CU Anschutz Cancer Center.
When a brain metastasis is detected, a neurosurgeon is immediately consulted. Breeze participates in a weekly conference with specialists from across campus, where new drugs and targeted therapies are discussed.
“The general mentality is that we are going to aggressively treat brain metastases,” Breeze says.
While survival rates for melanoma patients are improving, Breeze notes that the level of care offered at a large academic institution is not available to everyone in the country.
“If you are at a major center, melanoma patients with brain metastases can survive for many years,” Breeze says. “There are many barriers to Americans living in rural areas preventing them from accessing the state-of-the-art treatment offered in cities.”
Breeze recently had a routine follow-up appointment with a melanoma patient who was first treated in 1998. That patient is cancer-free today, even after a recurrence in 2011. Without the care offered by Breeze and Robinson, the patient likely would not have survived cancer. Together, Breeze and Robinson challenged the 1990s standard of care for melanoma patients.
Breeze, who was once considered ahead of the curve with his treatment of melanoma brain metastases, now sees a rising generation of oncologists passing him.
“When I was in medical school, residency, and as an early attending, all we could really hope to do was prolong quality of life when we treated brain metastases,” says Breeze. “Now if a patient comes to see me, I can often control their brain metastases for long periods of time, and the patient's survival may hinge on the effectiveness of the systemic therapy.”
Over his career, Breeze and colleagues across neurosurgery, medical oncology, and radiation oncology have helped bring cures, longer lives, improved quality of life, and hope to thousands of melanoma patients.
“Things are always changing with new technology,” he says. “If the last 40 years are any indication, the future for melanoma patients is very bright.”