New hope for patients with breast cancers resistant to tamoxifen

Researchers have found a new family of therapeutic agents that interferes with the ability of estrogen to stimulate the growth of breast cancer cells. The results of the new study will be presented by Nicole Patterson at The Endocrine Society's 90th Annual Meeting in San Francisco.

The cell-based study suggests that a small-molecule therapeutic called TPBM and related compounds are likely to be effective against breast cancers that depend on estrogen to grow (called estrogen receptor-positive) but that are resistant to current therapies, team leader David Shapiro, PhD, said.

Shapiro, a biochemist at the University of Illinois at Urbana-Champaign, said at detection, about two-thirds of breast cancers are estrogen receptor-positive, and virtually all of these cancers become resistant over time to the breast cancer drug tamoxifen. In some tamoxifen-resistant tumors, tamoxifen begins to act like estrogen and can actually stimulate tumor growth, he explained.

Therefore, researchers are trying to find new ways to block resistance to drugs such as tamoxifen. Shapiro's team developed a technique to screen for chemical compounds that would inhibit the ability of estrogen and the estrogen receptor protein to bind to DNA and turn on gene expression in breast cancer cells.

"We targeted a different step in the pathway of estrogen action, one that is not targeted by current therapeutics," Shapiro said.

They then tested various agents in estrogen receptor-positive breast cancer cells in the laboratory. The team identified a family of compounds related to TPBM that Shapiro said inhibited the estrogen-dependent growth of breast cancer cells.

"TPBM is highly targeted and has little or no toxic effect on other cells-those that don't depend on the estrogen receptor," Shapiro said. "Also important, these compounds are effective in breast cancer cells in which tamoxifen acts like estrogen."

Thus, these compounds might prevent tamoxifen-resistant breast cancer from becoming more aggressive. However, Shapiro cautioned that their research is in the early stage. A future step will be testing the new estrogen receptor inhibitors in animal models of breast cancer.