BCRF duo take next step in determining tumor's "instruction kit"
Answers to why aspirin lowers risk on hormone receptor-positive cancers emerging
About 75 percent of all breast cancers are "estrogen-receptor positive." These tumor cells carry receptors for estrogen. When estrogen binds, or attaches, to these receptors it starts a cascade of biochemical signaling resulting in tumor growth.
Researchers also know that aspirin seems to aid in protecting women from developing estrogen receptor-positive cancers. Now, BCRF researchers Andrew Dannenberg, MD, of Weill Cornell Medical College in New York and Clifford Hudis, MD of Memorial Sloan-Kettering Cancer Center in New York are learning why. They and their colleagues at Weill Cornell have identified two cellular receptors called EP2 and EP4 that can activate estrogen production in fat and breast cancer cells.
The way EP2 and EP4 work involves aromatase, an enzyme that manufactures estrogen. And that gets back to the aspirin connection. Numerous studies, including some by Dannenberg and his colleagues, have shown that non-steroidal anti-inflammatory drugs (NSAIDS), a class of medicines that includes aspirin, hamper aromatase activity. This effect is thought to explain, at least in part, how aspirin lowers risk of breast cancer.
Since not everyone can take aspirin and other NSAIDS, and the side effects of taking them may affect other aspects of health, knowing the role of EP2 and EP4 is important.
"We are always looking for new points of entry in the estrogen pathway that can shield women from breast cancer without raising risk in other areas," says Dannenberg.
"Pinpointing the role of these receptors is like adding two important new parts to the tumor's 'instruction kit'," he says. "You have to understand all the players involved if you hope to uncover weakness to fight or prevent the disease."
What's more, EP2 and EP4 offer new targets for pharmaceutical research. "Drugs that work against EP2 and EP4 could be developed for prevention" says Hudis. "In the end, our goal is to identify safe ways to truly prevent breast cancer and this work provides a clue as to how we might accomplish this."
