Early diagnosis is key when it comes to breast cancer prevention. The posters, ribbons, rallies, and races are partly meant to remind us that the earlier doctors find a tumor, the less likely it is to metastasize.

Once a doctor takes a tissue sample of the tumor, the estrogen receptor is their best clue that it's cancer. This receptor is a protein that acts based on hormonal messages it gets from the blood. And up until now, progesterone receptors were only used to confirm the protein was active. But according to a new study published in Science Advances, progesterone may be able to determine if a tumor is cancerous as well as estrogen.

Researchers found that progesterone receptors can dramatically change how estrogen receptors interact with DNA. When it's exposed to estrogen and progesterone, receptor proteins work with different binding sites on the human cell, which then affects estrogen's activity. According to study author Dr. Geoffrey Greene, researchers have been paying more attention to this "cross talk" between these receptors for years now.

“We now know that this relationship can be better understood and potentially exploited,” he said in a statement. “This observation is important be cause more than two-thirds of breast cancers contain both estrogen and progesterone receptors.”

Previous studies have demonstrated that estrogen receptors react to the primary female sex hormone, estradiol, by activating genes that nudge cancer cells into growing and replicating. The cells divide faster and live longer, which results in a more advanced state, Greene explained.

The study concluded that when progesterone or progestin is added, an entirely new set of binding sites opens up, allowing the estrogen receptor to work in conjunction with progesterone receptors. The process stops cell reproduction and survival and "our data further suggests that, despite the historical bias toward the effects of estrogen on the estrogen receptor," Greene said. "It’s the progesterone receptor that dominantly controls estrogen activity when both receptors are present and activated."

During the study, Greene and his colleague Haral Singhal inhibited the activity of both estrogen and progesterone receptors in three groups of mice by treating them with either the estrogen receptor antagonist tamoxifen, an experimental progesterone receptor antagonist called CDB4124, or a placebo. Predictably, tumors in untreated mice grew quickly. Tamoxifen halted tumor growth, but did not shrink them, while CDB4124 had a more complicated effect: It caused the tumors to shrink at first, but after 35 days, they began growing again and ended up 50 percent larger than their original size. A combination of the two antagonists seemed to be the golden ticket: tumors showed “virtually full regression,” according to Singhal.

“These findings,” the study reads, “emphasize the clinical value of assessing both progesterone receptor and estrogen receptor expression in breast cancer samples.”

Source: Singhal H, Greene M, Tarulli G, Zarnke A, Bourgo R, Laine M, et al. Genomic Agonism and Phenotypic Antagonism Between Estrogen and Progesterone Receptors in Breast Cancer. Science Advances. 2016.