By Ms. Erin Bolling (Army Medicine)November 2, 2018
If battling cancer isn't frightening enough, living in fear of metastatic recurrence means the battle never really ends. For the one in eight patients who develop breast cancer, the greatest fear may be the possibility of future metastases to the lungs, liver, bones and brain. Even when breast cancer is "gone," it's never far from the mind of the survivor.
The World Health Organization deems breast cancer a global burden, as it remains the most common cancer among women worldwide. The WHO estimates over 250,000 women in the U.S. alone will be diagnosed each year; in response to this, breast cancer advocates continually demand increased funding for research to improve health outcomes and save lives through primary prevention, better detection methods, and more effective and safer treatment options. Efforts such as these helped to establish the Breast Cancer Research Program in 1992, which evolved into the Congressionally Directed Medical Research Programs. The CDMRP BCRP now works to support a world without breast cancer through high-impact research.
When cancer metastasizes, it keeps the same name as the primary cancer. So when breast cancer spreads to the brain, it is called metastatic breast cancer, not brain cancer.
"Breast cancer metastasis to the brain is particularly devastating to the patient because there are very limited treatment options for this advanced stage of the disease," said Dr. Gayle Vaday, BCRP program manager.
"Over the years, the BCRP has invested nearly $70 million in research specifically focused on understanding brain metastasis and developing treatment strategies," said Vaday. "Seminal findings in early preclinical studies funded by the BCRP have led to two Phase I clinical trials that are currently testing new therapeutics to prevent and treat brain metastasis."
Dr. Patricia Steeg, principal investigator at the National Cancer Institute, was awarded a Breast Cancer Center of Excellence Award by the BCRP in 2005 to study the eradication of brain metastases of breast cancer. This effort sought to increase the number of brain researchers looking into breast cancer and to build an infrastructure of data. Steeg's preclinical work accomplishments, through the BCRP CoE Award, led to Phase I and II clinical trials for a secondary prevention of Human Epidermal growth factor Receptor 2 positive (or HER2+) brain metastases.
"When I started working on brain metastasis of breast cancer, we had almost nothing to work with -- few if any model systems, human craniotomy specimens, no knowledge of the blood-brain barrier, et cetera," said Steeg.
"We needed a village to move forward, made up of oncologists, neuropathologists, neurosurgeons [and] molecular biologists," she continued. "This grant allowed me to recruit 20 investigators in the U.S. and Canada with the needed skills. It provided the base funding for each to get started in this new field, and they, in turn, applied for and received subsequent funding. It created a collaborative group."
This collaborative group was able to develop the first comprehensive data on drug uptake into experimental metastases using pharmacology and imaging approaches, which demonstrated that the blood-tumor barrier is a significant obstacle to drug efficacy. Also, it characterized for the first time the molecular composition of the blood-tumor barrier and demonstrated it can be altered.
This award also funded the testing of drugs for potential prevention or shrinkage of brain metastases pre-clinically and explored the molecular biology of brain metastases using both the model systems and human craniotomy specimens.
This important data was disseminated to patients via a Website (BrainMetsBC.org) that was established by the consumer advocates who were part of the Breast Cancer Center of Excellence team. The Website received over a million hits per year. Steeg shared that the involvement of consumer advocates was vital in this work.
"We had two-to-three advocates at any time, and they were busy," said Steeg. "Advocates started off each meeting with presentations, to remind us that this was not an academic issue, and to prioritize our research agenda. They created a Website and spoke to many other organizations on our behalf. They helped me identify what avenues were most promising."
This involvement of consumers has always been a staple for the CDMRP, and it is a reflection of their historical importance since the very beginning. The BCRP is committed to and it will continue to seek high-impact research to address the urgency of ending breast cancer.
"The BCRP challenges the scientific community to pursue innovative research that will translate to the clinic, and to make progress toward eliminating the mortality associated with metastatic breast cancer, said Vaday. "Ultimately, we are hopeful that this critical effort will save the lives of women and men with metastatic disease."