Home Life Style Genetic mutations may the cause for treatment resistance in breast cancer

Genetic mutations may the cause for treatment resistance in breast cancer

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A new study led by researchers at the University of Michigan Comprehensive Cancer Center and published in Nature Genetics, brings new important information about the genetics of breast cancer. The researchers found that breast cancer patients who took anti-estrogen therapy developed a certain type of genetic mutation and that  this mutation could cause resistance to treatment.

This research actually is based on a program called Mi-ONCOSEQ and developed by UM Comprehensive Cancer Center. This was a program that involved DNA and RNA analysis in all patients with advanced cancer. The aim of this DNA sequencing was to identify genetic mutations involved in cancer; researchers also hope to develop new targeted therapies based on these results.

 

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Researchers investigated 11 patients with estrogen receptor positive breast cancer in an advanced stage. Estrogen receptor positive cancer is the most common type of breast cancer; the presence of estrogen receptors shows that this cancer is influenced by hormone therapy; however there are cases when patients develop resistance to treatment. DNA sequencing revealed that 6 of these patients had mutations in the estrogen receptor. It should be noted that all these patients were treated with aromatase inhibitors, drugs that interfere with estrogen production. What is really interesting is that these mutations did not exist before patients start this therapy. This means that this treatment triggered these genetic mutations.

Lead study author, Dan Robinson, Ph.D., research assistant professor of pathology at the UM Medical School, said this is the means by which these tumors become resistant to hormonal therapy. He explained that these mutations activate the estrogen receptor when there is no estrogen as happens when a patient takes aromatase inhibitors. According to Robinson, an on-switch is essential for estrogen receptor. This switch prevents the effects of aromatase inhibitors therapy;  in other words the switch prevents estrogen receptor signaling to be shut down. When patients with breast cancer patients become resistant to treatment, there are few treatment options left.

Study co-author Anne F. Schott, MD, associate professor of internal medicine at the UM Medical School, said that they tried for a long time to find out why patients become resistant to the anti- hormone therapy. “This finding sheds an entirely new light onto the problem. Now, we can look at how these estrogen receptors function and begin to develop drugs to shut down or attack this mutation, ” she said. Researchers also believe that blood tests will be able help monitor patients and detect these mutations to change the treatment before resistance develops.

 

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