Published today in Science Advances, the study reports that treatments aimed at the progesterone receptor, a protein activated by progesterone, could prolong life in women with estrogen-driven breast cancer beyond current standard treatments which target the estrogen receptor alone. These standard treatments are tamoxifen or aromatase inhibitors.
“About 75-80% of breast cancers are driven by the female hormone, estrogen,” says Professor Wayne Tilley, Director of the University of Adelaide’s Dame Roma Mitchell Cancer Research Laboratories. “One of the first clues pathologists look for in tissue from a newly diagnosed breast cancer patient is the estrogen receptor, a protein in tumour cells that transmits the growth-promoting signals of estrogen hormones in the body. They also look for the presence of progesterone receptors, primarily to confirm that the estrogen receptor is active.”
The role of estrogen in driving tumour growth in breast cancers is well established, but the role of progesterone is the topic of much controversy.
The study, led by Professor Geoffrey Greene at the University of Chicago in collaboration with Professor Tilley at the University of Adelaide, employed a special technique for modelling breast cancer developed by the Adelaide group. This model allows researchers to test potential new treatments directly on breast cancer tissue donated by patients.
Building on earlier work by the University of Adelaide and the Cancer Research UK Cambridge Institute, the new study independently confirms and provides new insight into how progesterone receptors reprogram the actions of estrogen receptor, with an overall “braking effect” on tumour growth.
“We have known for some time that the progesterone receptor plays an important role in breast cancer, but gaps in our knowledge of the function of this receptor in breast tumours have limited the potential to develop new treatments,” says Professor Tilley. “This independent study provides important preclinical validation for initiation of clinical trials testing progesterone in combination with current standard-of-care therapy.
“Use of progesterone for treatment of breast cancer has raised considerable controversy because of past studies showing some negative effects of synthetic versions of progesterone used in hormonal therapy for postmenopausal women. In our studies, we are using natural progesterone, or forms of this hormone that are biologically identical to the natural hormone, and testing it on breast cancer tissue taken from women with cancer.”
The researchers also identified a new progesterone receptor targeting drug that not only opposed the action of estrogen in breast cancers to halt tumour growth, but actually caused the tumours to regress. This new drug is now poised to enter the clinical trial phase.
“Our study helps resolve the controversy over whether progesterone is good or bad for women with breast cancer,” says Dr Theresa Hickey, Senior Research Fellow in the Dame Roma Mitchell Cancer Research Laboratories. “The next question is how best to exploit it for the benefit of women with this disease.”
Professor Tilley says that a clinical trial will start in the UK this year. “We have also initiated proposals for a trial in Australia to thoroughly test this potentially life-extending treatment for breast cancer patients,” he says.