New Models of Drug-Resistant Breast Cancer Show Hope for Future Treatments

A recent study looks at how human breast tumors transplanted into mice that work as models of metastatic cancer could potentially provide insight into how to treat breast cancer that no longer responds to drugs used to treat them.

According to researchers from the Washington University School of Medicine, they found that these transplanted tumors maintain the same genetic errors caused by original cancer, even when growing in mice. And as mice carry human tumors, they help identify drives of the tumor growth.

Lead study author Matthew J. Ellis, M.D., Ph.D., presented the findings on Dec. 12 at the San Antonio Breast Cancer Symposium, via the titled research "Patient-derived xenograft study reveals endocrine therapy resistance of ER+ breast cancer caused by distinct ESR1 gene aberrations."

"Research over the past 20 years has shown tantalizing hints that patients whose disease stops responding to anti-hormonal agents have changes in the estrogen receptor," said Ellis, who sees patients at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University, via a press release. "And we found all three types of 'gain-of-function' mutations in the estrogen receptor gene ESR1 in the tumor samples."

Their study focuses on estrogen receptor (ER) positive breast cancer-the most common type-that almost is resistant to standard treatment. However, unlike ER-positive cancers that respond well to the treatment, these drug-resistant types often spread elsewhere in the body even with aggressive use of therapy. Some women with breast cancer respond well to treatments while others don't, and it's not certain why.

However, researchers found three different types of mutations via estrogen receptor in patients whose cancer was resistant to anti-hormone therapy, with one mutation being a gene amplication that copies ESR2 gene and the other part of the receptor that binds estrogen. The third is a translocation in which half of the estrogen receptor gene is swapped for an unrelated gene from a different part of the genome.

"We can now categorize estrogen receptor-positive breast cancer that has evolved resistance into four categories: point mutated, translocated, amplified and none of the above," he said, via the release. "We're planning clinical trials to study different treatment strategies for each of these types."

The scientists are hoping to use gene amplification to explain why some tumors become resistant to estrogen-lowering drugs. 

More information regardnig the study can be found via the Cell Reports.