Discovery of progesterone receptor’s role in breast cancer could have treatment implications for approximately half of all patients

The addition of the hormone progesterone to breast cancer treatment could benefit approximately half of breast cancer patients, suggests a new study carried out at Cancer Research UK’s Cambridge Research Institute (UK) and the University of Adelaide (Australia). The work, published this week in Nature, demonstrates how the progesterone receptor (PR) interacts with the estrogen receptor (ER) in malignant cells to slow tumor growth. Individuals with breast cancer that express the PR and ER are associated with better outcomes, yet the role of the PR in these improved outcomes remained elusive for decades.

“We’ve used cutting-edge technology to tease out the crucial role that progesterone receptors play in breast cancer – a mystery that has baffled scientists for many years,” reported Jason Carroll, lead investigator from Cancer Research UK’s Cambridge Research Institute. “This important laboratory research helps explain why some breast cancer patients have a better outlook. Crucially, it provides a strong case for a clinical trial to investigate the potential benefit of adding progesterone to drugs that target the estrogen receptor, which could improve treatment for the majority of hormone-driven breast cancers.”

Specifically, the team uncovered that expression of the PR is not merely a result of ERα-induced gene expression in breast cancer cells, but that it is also able to associate with and modulate the behaviour of ERα. When there are appropriate agonist ligands present, the PR can work to direct ERα chromatin binding events, resulting in gene expression patterns that are connected with positive clinical outcome. They also demonstrated that progesterone was able to inhibit cell growth in ERα-positive breast cancer xenografts – an effect that was amplified with the addition of an ERα antagonist.

Emma Smith of Cancer Research UK commented: “This exciting study in cells shows how a cheap, safe, and widely available drug could potentially improve treatment for around half of all breast cancer patients. Thanks to research, almost 70% of women now survive breast cancer beyond 20 years – but so much more must be done and we won’t stop until we find cures for all forms of the disease.”

Sources: Mohammed H, Russell IA, Stark R et al. Progesterone receptor modulates ERα action in breast cancer. Nature doi: 10.1038/nature14583 (2015); Cancer Research UK press release