New breast cancer treatment shows promise in human trial

An international group of researchers have conducted a clinical trial of a new breast cancer drug with fewer side effects, which may open up the possibility for its use in breast cancer prevention.

About 80% of breast cancers are estrogen receptor (ER) positive, which means that the hormone estrogen tells the tumour cells to grow.

Hormone therapy to block estrogen activity in the body or inhibit the estrogen receptors’ ability to recognise it has remained a main treatment strategy to tackle these breast cancers for decades.

However, while successful initially these treatments can cause severe side effects and treatment-resistant progression of the disease is common. 

A new global study in postmenopausal women with ER-positive breast cancer has found that there might be a less toxic way to treat it.

The oral drug enobosarm was found to have antitumour activity while being well-tolerated by patients.

Unlike previous hormonal therapies, enobosarm works by stimulating the androgen receptor (AR). As the name suggests, androgen receptors recognise androgens – hormones usually thought of as “male” sex hormones because they are responsible for encouraging male secondary sex characteristics.

But small amounts of androgens are also found in the female body and androgen receptors have previously been shown to act as tumour suppressors in ER+ breast cancer in pre-clinical research.

“The effectiveness of enobosarm lies in its ability to activate the AR and trigger a natural defence mechanism in breast tissue, slowing the growth of ER+ breast cancer, which relies on the hormone estrogen to grow and spread,” says Wayne Tilley, Director of the Dame Roma Mitchell Cancer Research Laboratories at the University of Adelaide, and senior co-author of the new study in The Lancet Oncology.

“This clinical study is supported by our pre-clinical research, previously published in Nature Medicine, which established that the AR is a tumour suppressor in both normal breast tissue and ER+ breast cancer.” Cosmos reported on the research in 2021.

The most recent study assessed the efficacy of enobosarm in 136 postmenopausal women with advanced or metastatic ER-positive, HER2-negative breast cancer. HER2 is a protein found on some breast cancers that help the cells grow quickly.

The researchers found that enobosarm showed antitumour activity and did not adversely affect quality of life or cause masculinising symptoms.

“Our findings are very promising. They demonstrate that stimulating the androgen receptor pathway with enobosarm can be beneficial,” says senior co-author and study Principal Investigator Dr Beth Overmoyer from the Dana-Farber Cancer Institute (DFCI) in the US.

“This is the first time a non-estrogen receptor hormonal treatment approach has been shown to be clinically advantageous in ER+ breast cancer.

“The study supports further investigation of enobosarm in earlier stages of breast cancer as well as in combination with targeted therapies, such as ribociclib, a CDK 4/6 inhibitor.” 

Co-author Dr Stephen Birrell, a molecular and surgical oncologist and clinical professor at the University of Adelaide, adds that the data strongly encourages more clinical trials for AR-stimulating drugs in treating AR-positive and ER-positive breast cancer.

“The fact that this drug is well-tolerated also opens possibilities for its use in breast cancer prevention,” he says.

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