Possible genetic origins of breast cancer that spreads to the brain have been uncovered, according to a first-of-its-kind study.
The compendium of genetic targets uncovered by the Translational Genomics Research Institute (TGen) in Phoenix, Arizona, now can be used to identify potential new methods of diagnosis and new drug therapies for the estimated 45,000 patients in the U
.S . each year whose cancer spreads from the breast to the brain.
three-year study is significant since these patients currently have few treatments options—only surgery and radiation—and they usually are ineligible for clinical drug trials. Their prognosis is poor, with fewer than 2% surviving more than two years
“This is really a significant problem and a huge unmet need. We now want to dig deeper and uncover more specific genomic links and study new ways to treat these patients so we can improve outcomes,” said the study’s lead author Bodour Salhia, PhD, of TGen.
After lung cancer, breast cancer is the second most common cancer that spreads to the brain. Chemotherapy generally has not been used to treat brain cancer, because of the blood-brain barrier that exists between the bloodstream and the cerebrospinal fluid surrounding the brain. However, some small molecule drugs can cross this barrier and form the basis of targeted therapies.
The overall goal of the TGen study was to look at genomic and epigenomic events to understand the causes of breast cancer brain metastatic lesions, and to identify potential new therapeutic targets.
The TGen team performed deep genomic profiling, integrating gene copy number, gene expression, and DNA methylation datasets on a collection of 35 breast-brain metastases samples. The study, published in PLOS ONE (2014; doi:10.1371/journal.pone.0085448), is the first of its kind to incorporate all of those avenues of inquiry in the study of this disease.
Some of the common genetic alterations identified in the study were gains and losses in chromosome 8, as well as cell proliferation and cell-cycle progression—key mechanisms of cancer caused by genetic alterations—linked to the genes AURKA, AURKB, and FOXM1.
“This groundbreaking study sets the stage for more exacting research, using the latest genomic technologies and aimed at developing new therapies that could help the tens of thousand of patients who urgently need our help,” said co
–senior author Nhan Tran, PhD, also of TGen.