By Musa Mayer
From Fear to Hope
New research efforts aim for better understanding and treatment of brain metastases
By Musa Mayer
If you ask women living with metastatic breast cancer what they fear most, brain metastases are high on the list. “I thought it would mean that my death would be almost immediate,” says Claudia Feigner, who was diagnosed initially with a single brain metastasis, then with another one a little more than a year later. “Although, death would be preferable to me than losing my mind and living.”
Feigner is one of an increasing number of women whose cancer is controlled outside the brain by the drug Herceptin (trastuzumab), but whose central nervous system remains vulnerable to the disease. Studies estimate that 25 percent to 50 percent of women on Herceptin who have metastatic breast cancer that is HER2-positive—which means their tumor cells have HER2 proteins that the drug can target—will develop brain metastases. But because the Herceptin molecule is large, it cannot penetrate the protective blood-brain barrier formed by the closely linked cells lining the brain’s circulatory system. This barrier, along with efficient “pumps” that remove toxins from cells, prevent most breast cancer treatments that work elsewhere in the body from entering brain tissue.Patient advocates Musa Mayer and Helen Schiff, working with Patricia Steeg’s team, have launched BrainMetsBC.org, a website for survivors and caregivers who are dealing with brain metastases, and which provides information about promising research results.
With the majority of life-prolonging drug therapies for metastatic breast cancer not effective in the brain, radiation therapy—and, less frequently, surgery—remain the primary treatments for brain metastases. But while whole-brain radiation can help control the disease in the short term, it can be toxic and can’t be repeated if there is a recurrence. More targeted radiation can’t be used if there are numerous metastases; it is also associated with higher rates of recurrence than whole-brain radiation.
Because so little is known about the permeability of drugs into the brain, the development of new therapies to treat brain metastases has been a stab in the dark, says molecular biologist Patricia Steeg, who leads the Women’s Cancers Section of the Laboratory of Molecular Pharmacology at the National Cancer Institute (NCI), and who has studied metastases for 20 years. Without samples of patients’ brain metastases for genetic analysis, or experimental studies on animals that are given brain metastases in the lab, identifying drug targets on tumor cells was impossible. “We had no resources. We had no mouse models, and we certainly had no tissue,” she says.
Steeg decided to build the research infrastructure to start developing new treatment strategies. For the last two years, under her direction, an interdisciplinary team of 23 scientists, physicians and patient advocates has been investigating new treatments for brain metastases. Funded by a grant from the Department of Defense’s Breast Cancer Research Program, the research group—designated a Center of Excellence—includes molecular biologists who do gene analyses of tissue samples and study mouse models of brain metastases, experts in the permeability of the blood-brain barrier, as well as oncologists, neuropathologists and neurosurgeons who examine new and existing treatments.
Two years after her diagnosis with brain metastases, Feigner reports that she is still doing well. She offers encouraging words to women experiencing what she once so feared, “There is much hope for successful treatment of brain mets and prolonged meaningful quality of life.” Meanwhile, the new Center of Excellence is laying the groundwork to make Feigner’s experience with brain metastases the rule, rather than the exception.