Brain Metastases: Treatments, Emotions and Research Directions
Published in the Summer 2014 issue of LBBC's Newsletter, Insight
Cathy Spencer, of Calgary in Alberta, Canada, was receiving chemotherapy and trastuzumab (Herceptin) for stage IIIC HER2-positive breast cancer in February 2008 when she began having vision problems and other difficulties. She called her medical oncologist, thinking she might need new eyeglasses.
Her oncologist ordered a CT scan of the brain and results showed a large brain metastasis, or brain met, a spread of breast cancer. There were several treatment options, and her oncologist and neurologist spoke about how surgery could help.
“It was quite a blow, hearing that it had spread to my brain,” says Cathy, who was 45 at the time and had two children, aged 8 and 12. “I had 100 per cent faith in my doctors, but I still went home and cried for days on end.”
After the tumor was removed, Cathy had whole–brain radiation therapy, WBRT, or radiation of the entire brain. It was given tolower her risk of developing new brain mets. More than 6 yearslater, the disease is stable, with no further spread of the cancer.
Breast Cancer Brain Mets
If you fear brain mets, you are not alone. It’s common to worry about these tumors, or lesions, that may affect the brain’s ability to control movement, speech and thinking. Plus, brain mets have been considered a sign of a poor medic al outlook.
Though brain mets are a serious condition, fears about what will happen to you if cancer spreads to the brain “may be unfounded,” says Musa Mayer, MS, MFA, a patient and research advocate with AdvancedBC.org and BrainMetsBC.org. “We have seen women who live years beyond a brain mets diagnosis and do very well.”
As more effective breast cancer treatments become available, survival rates are increasing, along with the number of people developing brain mets. Most brain mets are found after metastases develop in the lungs, liver or bones, but some are a first sign of disease spread.
Brain mets can form in a person with any breast cancer subtype, but are more likely to arise in those with HER2-positive or triplenegative disease.
Part of the fear caused by the diagnosis is “based on what it was like to get a brain met in the past,” Ms. Mayer says.
Today, because breast cancer can be well controlled throughout the body, people who develop brain mets are healthier and stronger and can often benefit from improved approaches.
“We now have some tools we didn’t have several years back,” says Carey K. Anders, MD, a medical oncologist at UNC Lineberger Comprehensive Cancer Center in Chapel Hill. While once there was little research taking place, now there are more clinical trials and more scientists exploring new avenues of study.
“At least half, if not more, of treated brain mets never come back, and patients don’t die…because of progression in the brain,” says Ms. Mayer. “I think [knowing] that can be reassuring.”
Diagnosis and Treatments
Magnetic resonance imaging, or MRI, a scan that uses a magnetic field and radio waves to show images of the brain, usually confirms the presence of brain mets. Treatment depends on how many tumors are found and their sizes and locations, as well as the person’s symptoms, strength and function.
For one or two large brain mets, doctors can perform a surgery known as craniotomy.
“Brain surgery sounds terrifying to most people, but it is very safe,” says Ganesh Rao, MD, a neurosurgeon at The University of Texas MD Anderson Cancer Center in Houston. “If you have a lesion putting pressure on the brain, you take it out. We expect to see relief immediately.”
Recent advances in technology pinpoint tumor location and help avoid surgical damage to vital areas of the brain.
For years, surgery was followed by WBRT to reduce the risk of regrowth of the cancer. That happens less often now as studies show radiation of the whole brain may cause long-term cognitive problems.
“There has been a trend away from WBRT,” Dr. Rao says. “When we make that decision [to use it], it’s not made lightly. Sometimes it has to be done.”
Cathy describes her recovery from craniotomy as easy, because the only pain was from a headache and she was hospitalized for just 2 days. Chemotherapy was stopped before surgery, but she continued to take trastuzumab and also had WBRT.
Stereotactic Radiosurgery (SRS, Gama Knife, CyberKnife, others)
This kind of localized radiation has various names, but the methods of delivery are similar. A same-day procedure, stereotactic radiosurgery, or SRS, is used with fewer than four or five small tumors. Despite its name, SRS does not involve surgery or cutting the skin. Instead, in one session beams of high-dose radiation are delivered directly to each tumor.
Brain mets may take several weeks to shrink from radiation. As tumors die off, they can leave necrotic, or dead, tissue, which may be decreased with steroids, surgery or other therapies. WBRT may follow SRS, but that is less common now. SRS may be used again if other lesions develop.
Lori Prashker-Thomas, 42, from Wilkes-Barre, Pennsylvania, is receiving 3D conformal radiation therapy, which shapes radiation to the tumor to spare healthy tissue, to shrink three brain mets so they can be removed. Diagnosed in 2010 with stage II, hormoneand HER2-positive disease, Lori carries the BRCA2 gene mutation.
After brain mets were found in late 2013, she began radiation, which was to happen daily for 25 weekdays. She is receiving only three sessions weekly due to skin irritation, burning and pressure. “Right now, I seem to be OK. I’m just tired,” she says.
Whole–Brain Radiation Therapy
When there are five or more brain mets, the entire brain is radiated. WBRT treats the mets seen on imaging scans, as well as undetected micrometastases, or small cancer cells, that could become larger.
The WBRT dose, which also radiates healthy brain tissue, is less than the SRS dose but is given over a longer period—often as daily weekday sessions for 2 weeks. Short-term side effects include hair loss, nausea and profound fatigue that lasts for about a month.
While WBRT works well at treating brain mets, cognitive difficulties such as memory loss and confusion may appear over time, even years later. This long-term effect has become more evident as people live longer. Recent research shows that taking memantine (Namenda), a medicine for Alzheimer’s disease, during WBRT results in less cognitive decline.
WBRT also may produce short-term memory loss. “It gets better at 4 months and continues to improve as time goes on,” Dr. Rao says. Researchers are exploring a technique to protect the hippocampus, the part of the brain that controls short-term memory, during WBRT.
Laureen Brock was 49 and almost 2 years past a diagnosis of stage I, triple-negative breast cancer when diagnosed with a large brain met. She had surgery and WBRT, a common approach to brain mets at that time.
“I have no [evidence of] cancer now and I’ve hit the 5-year mark, so I feel pretty good about it,” says the Chattanooga, Tennessee, woman. But it has not been an easy road. After surgery, Laureen began having seizures. She suffers from memory loss, depression and vertigo.
Emotional and Social Impact
Brain mets can be challenging, whether you already had metastatic disease or it is your first diagnosis. Lori had added concern: her sister, who also carried the BRCA2 gene mutation, had breast cancer brain mets and died 11 years ago.
“There are days I don’t want to get up,” Lori says, “I just want to sit and cry. I allow myself one day a month…Do it and get it over with. There are months I don’t use it and I’m grateful.”
Brain mets may affect work life. As a self-employed photographer, Lori cancelled some jobs requiring travel but sees local clients. “I have to continue working,” she says.
After brain met surgery and radiation therapy, Cathy returned to the dealership where she sold cars, but she switched to parttime office work. “I couldn’t trust myself to do calculations and data,” says Cathy, who no longer works.
Laureen was a nurse but now lives on Social Security disability. She broke her neck in a car accident last year. Doctors were uncertain if she had a seizure; she doesn’t remember the accident at all. “I never found a ‘new normal,’” she says.
Brain mets can seem frightening. Yet, many people find support by talking with others who have brain mets or another metastatic diagnosis. Cathy spoke at her local hospital and belongs to a metastatic breast cancer support group. She gives phone support to a woman with advanced disease and advocates for attention to metastatic breast cancer and brain mets.
Lori takes part in I Picture Hope, a network providing free photo sessions to women with breast cancer. She connects online with members of Camp Bravehearts, which offers retreats for women with cancer. (For more information visit facebook.com/iPictureHope and braveheartscamp.org.)
“I get a tremendous amount of support from those ladies,” she says. “My husband and daughter are also truly amazing, and my friends.”
At the National Cancer Institute, Patricia S. Steeg, PhD, and her lab team are exploring how the blood–brain and blood–tumor barriers keep medicines from reaching brain mets. They recently found that a chemotherapy used to treat glioblastoma, a type of brain cancer, worked in mice to prevent human breast cancer brain mets. “That was the biggest shock,” Dr. Steeg says. It is not yet known when clinical trials with humans will begin.
Unlike in the past, now some trials accept participants diagnosed with brain mets. Researchers are looking at ways to predict risk and find effective treatments, including how to make existing breast cancer medicines better able to enter the brain.
“There’s certainly more work going on now,” says Nancy U. Lin, MD, clinical director of breast oncology at Dana-Farber Cancer Institute in Boston.
Brain mets trials once included people with several cancer types, but they have shifted. Now there are trials of targeted therapies, chemotherapies and other treatment approaches that enroll only people with breast cancer.
“There’s more focus now on breast cancer being distinct and on the disease subtypes,” Dr. Lin says. “I think that’s a good improvement.”
As Insight went to press, the American Society of Clinical Oncology, ASCO, issued its first guideline on treating brain mets in metastatic HER2-positive breast cancer. Treatment recommendations include surgery and radiotherapy, or both, depending on size and number of mets, and other criteria. Surgery, WBRT and systemic (whole-body) therapies that have shown activity in the presence of brain mets are advised for some. HER2-targeted systemic treatments, such as trastuzumab, have more difficulty reaching the brain than other areas of the body.
To find out about clinical trials recruiting those diagnosed with brain mets, go to BrainMetsBC.org or clinicaltrials.gov.