Researchers from the Washington University School of Medicine, the Mayo Clinic, the Baylor School of Medicine, and the MD Cancer Center have discovered that estrogen-deprivation therapy could potentially help treat estrogen-receptor positive breast cancer tumors, according to a news release from the Baylor School of Medicine.

The way this new therapy works is by changing mutations in the tumor population that the researchers looked at.

“The majority of ER-positive breast cancers are not a single tumor but more like a family of related tumors referred to as ‘sub-clones,’” Senior author Dr. Matthew Ellis, Professor and Director of the Lester and Sue Smith Breast Center at Baylor, stated in the release. “The tumors are like a large family. A family has the same genetic origin – the same parents – but each family member has distinct genetic characteristics.”

“The brothers and sisters are clearly individuals but they are also related. When we treat the tumor with aromatase inhibitors, an estrogen-deprivation therapy that lowers the levels of estrogen the tumor needs to grow, we are creating a situation where certain members in the tumor family are able to persist and grow while others perish. The surviving members of the tumor family are likely the ones that will cause future problems with recurrence,” Ellis said.

Prior to this research, scientists knew little about how aromatose inhibitors impact the genes and mutations within a tumor. The researchers looked at several sub-clones with a common origin, which means all of the samples came from the same “tumor family.” However, the scientists also discovered that some patients had multiple tumors of different origins.

Ellis clarified that some patients had two or more tumors that were growing closely together. These were called “collision tumors” and initially look like one family of cancerous cells, but actually start out at different origins. Patients with an unexpected relapse and an initial good prognosis after diagnosis often have undiagnosed collision tumors.

“In this study, we present a first answer to this question by studying 22 human breast cancer tumors scheduled for surgery,” explained Ellis. “To reduce tumor size before surgery, we treated the tumors with estrogen-deprivation therapy for four months. The tumors were then surgically removed. We analyzed in great detail the effect of estrogen-deprivation therapy on the gene mutation patterns of the tumors by studying the entire genomic structure – the whole genome – of each of the tumors on biopsies taken before and after estrogen-deprivation therapy.”

“In the post-treatment samples, we found many new mutations or enrichment of mutations present at low levels in the pre-treatment samples,” said Ellis. “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.”

Essentially, the results from this research suggest that treatment with aromatose inhibitors before any surgeries could actually bring better outcomes for breast cancer patients.

“Our results suggest that studying the genetic makeup of a tumor at diagnosis is not enough – periodically scanning the genome in several biopsy samples to understand how it is changing may help us evolve treatment strategies to match,” Author Dr. Christopher Miller, Research Faculty at the McDonnell Genome Institute, said in a public statement.

 

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