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New Molecule Discovery Shows Promise Against Tamoxifen-Resistant Breast Cancers

Potential therapy could be the next generation of treatments, researchers say

MONDAY, June 16 (HealthDay News) -- Researchers have identified a new group of compounds that might one day be added to the armamentarium of therapies designed to fight estrogen-fueled breast cancer.

"This is a potential new approach to treating hormonally sensitive tumors," said Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society. "If it proves to work with a lot of further research, then it does have potential as an important part of cancer research."

The study, by researchers from the University of North Carolina, Chapel Hill, the University of Colorado Health Sciences Center, Denver, and the University of Illinois, Urbana-Champaign, was presented Monday at the annual meeting of the Endocrine Society, in San Francisco.

The molecule, called TPBM, and related drugs may have a role in treating patients who have become resistant to other hormone-based therapies, such as tamoxifen.

"We have a large number of people who have estrogen receptor-positive breast cancer who respond wonderfully to hormone therapy. But, sometimes, after one or two years, the hormone therapy stops working," said Dr. Jay Brooks, chairman of hematology/oncology at Ochsner Health System in Baton Rouge, La. "[Then] we'll switch to something else. That works for about a year before the cancer progresses. So what is it that's happening in those cancer cells that they become resistant? Perhaps there is another mechanism in which we can try to keep cells in response, and this would perhaps be one of them."

Some two-thirds of all breast cancers are estrogen receptor-positive and therefore respond to hormonal treatments such as tamoxifen or the newer aromatase inhibitors.

Tamoxifen blocks estrogen receptors on breast cancer cells, while aromatase inhibitors interfere with the body's ability to produce estrogen.

But almost all cancers in this category eventually become resistant to tamoxifen and, in some cases, tamoxifen may even turn the tables and start acting like estrogen, thereby fueling tumor growth.

Through extensive laboratory testing, the study authors identified a group of compounds related to TPBM that interfered with estrogen's effect on breast cancer cells via a different pathway. The molecules work by affecting the way estrogen receptors interact with a woman's DNA, the researchers said.

TPBM has the advantage of being "highly specific" and therefore much less likely to have any unwanted effects on other cells. It also works against tamoxifen when tamoxifen starts fueling tumor growth, the researchers said.

"As we look forward with all of our research and our capabilities, we'll hopefully continue to discover new ways to exploit hormone sensitivity," Lichtenfeld said. "This may be the next pathway, although we can't say that for sure... Hormonal approaches to breast cancer continue to add, literally, years to lives."

More information

For more on treating breast cancer, visit the National Cancer Institute.

SOURCES: Jay Brooks, M.D., chairman of hematology/oncology, Ochsner Health Service, Baton Rouge, La.; Len Lichtenfeld, M.D., deputy chief medical officer, American Cancer Society, Atlanta; June 16, 2008, presentation, The Endrocine Society annual meeting, San Francisco

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