Treating human estrogen-receptor (ER)-positive breast cancer tumors with estrogen-deprivation therapy can change the spectrum of mutations in the tumor population, affecting treatment response, according to research published in Nature Communications.
While they are similar, ER-positive breast cancers are not a single tumor, but rather a collection of related tumors referred to as sub-clones. As such, each has distinct genetic characteristics that may react differently to varying forms of treatment.
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In a study led by Matthew Ellis, Lester and Sue Smith Breast Center at Baylor (Houston, TX), researchers looked at 22 human breast cancer tumors scheduled for surgery and treated them with estrogen-deprivation therapy for 4 months before having them removed. To analyze the effect of estrogen-deprivation therapy on the gene mutation patterns of the tumors, researchers studied the entire genomic structure of each tumor before and after treatment was administered.
“In the post-treatment samples, we found many new mutations or enrichment of mutations present at low levels in the pre-treatment samples,” Dr Ellis said of the results. “This means that under the environmental stress of the treatment, the tumors are spawning new sub-clones which subsequently can survive and grow despite therapy, and that is why we are having difficulty treating ER-positive breast cancer. We found this result for a majority of ER-positive breast cancers we studied.”
Further, while each patient in the study was diagnosed with only one tumor type, analysis of the cancer genome revealed that, in some cases, patients actually had two separate tumors growing in close proximity, which are called collision tumors and could explain why patients with initially favorable prognoses sometimes have unexpected relapses after surgical treatment. That could require a change to how patients are treated.
“If a patient with breast cancer has the tumor surgically removed, it won’t be possible to detect the cells with the genetic makeup most likely to be driving relapse,” Dr Ellis continued. “But, if, on the other hand, we start by treating the tumor with aromatase inhibitors before surgery for a few months, so we can track the behavior of that tumor, we would get a more complete picture of the cancer. We can potentially detect sub-clones that can cause relapse in the future.”
In their conclusion, researchers suggest that caution be exercised when interpreting clinical genomic results from a single core biopsy at a single point in time, as the genomic structure of tumors could change during the course of treatment. They also state that more research is needed in the form of clinical trials to arrive at a better understanding of breast cancer and how to treat it.
