Hormone therapy is a common and effective treatment for breast cancer, but some genetically complex tumors may become resistant to the treatment, according to a Washington University study.
Researchers studied 22 tumors before and after four months of treatment with aromatase inhibitors. The inhibitors block the production of estrogen, in hopes of reducing the size of the tumor before it is surgically removed. After analyzing post-treatment samples of the tumors, researchers found that the majority (18 of 22) exhibited an aggressive response to therapy, including mutations and “sub-clones” that were able to survive and grow despite the treatment regimen.
“Estrogen-receptor-positive breast cancers are not created equal,” said co-senior author Elaine Mardis, PhD, co-director of the McDonnel Genome Institute at Washington University in St. Louis. "Each woman's disease can have a range of responses to estrogen-lowering drugs.”
Just a single tumor was unchanged by the end of the treatment, and one tumor was completely missing a mutation that was present in 92 percent of the preliminary samples, showcasing the genetic malleability of the cancer.
This high rate of mutation means a single biopsy at diagnosis isn’t enough, according to first author Christopher Miller, PhD, an instructor in medicine at Washington University.
“Even single tumors can evolve in response to therapy very quickly. ... Periodically scanning a tumor’s genome to understand how it is changing may ultimately help us evolve our treatment strategies to match,” he said.
This additional analysis will likely tell clinicians just how much a tumor has changed—and whether further estrogen suppression treatment is likely to contribute to a lower risk of relapse.
Additionally, the study supported past research indicating that mutations in a gene called ESR1 are connected to the hormone therapy resistance.