30% of breast cancers currently don't respond to this type of estrogen-linked drug
MONDAY, Feb. 23 (HealthDay News) -- Researchers have found a way to "switch on" estrogen sensitivity in breast tumor cells, thereby making them vulnerable to the breast cancer drug tamoxifen.
If successful, the technique might someday allow breast cancer patients who don't respond to tamoxifen to benefit from the drug.
"We're excited by the results," said study author Caroline Ford, a member of the department of cell and experimental pathology at Lund University in Malmo, Sweden. "This has implications for the 30 percent of breast cancer patients who are estrogen-receptor negative who currently have a poor prognosis."
Not only might these tumors become amenable to tamoxifen, but they may also respond to other "endocrine" treatments such as aromatase inhibitors, which also interfere with estrogen production in the body.
"We are currently investigating this," Ford said.
The findings may also provide alternatives for the group of women who start out estrogen receptor-positive but later become negative and for whom treatments stop working.
The findings are published in this week's issue of the Proceedings of the National Academy of Sciences.
As Ford noted, a large minority of patients have breast cancer tumors that do not express estrogen receptors. Not only does this make them unresponsive to a variety of treatments now available for estrogen receptor-positive malignancies, but it indicates a more aggressive cancer in general.
Tamoxifen, which has been a gold standard of breast cancer treatment for decades, works by binding to the estrogen receptor. If there is no receptor, however, tamoxifen becomes useless.
Any means of allowing the three out of 10 women whose cancers don't respond to tamoxifen and other endrocrine therapies would be a big advance, experts say.
"[Research] groups have been looking to restore positivity, to open the door to treatment with tamoxifen and aromatase inhibitors," said Dr. Minetta Liu, a translational researcher and breast oncologist at Georgetown University's Lombardi Comprehensive Cancer Center in Washington, D.C. The Swedish team now "have a molecule suggested that may, in fact, succeed. The findings are very exciting," he said.
So far, however, these promising results have only been seen in the lab and would need to be confirmed in animal models. If those experiments are successful, human trials would come next.
So how does the new technique work? In prior trials, researchers had noticed an association between cells that didn't express the estrogen receptor and a loss of expression of Wnt-5a, a key signaling protein.
This led to a theory that Wnt-5a might regulate estrogen receptor levels and, in fact, this seemed to be the case. Re-establishing Wnt-5a signaling resulted in higher estrogen receptor levels in estrogen receptor-negative cells.
But, the authors pointed out, Wnt-5a is probably too large a molecule to be administered directly to patients.
But Foxy-5, a smaller molecule and a Wnt-5a analog (look-alike) developed in the laboratory, did the same job as effectively, the team said.
Ford, along with a co-author of the paper, has filed a patent for the effects of the Foxy-5 peptide on estrogen receptors.
In related research, another study in the same issue of PNAS found that a protein called lipocalin 2 can indicate how invasive a breast cancer is likely to be. Better yet, levels of the protein can be measured in urine.
Apparently, lipocalin 2 decreases estrogen receptor levels, which indicates the presence of more aggressive cancer, according to researchers at Children's Hospital Boston.
Testing for the protein could help doctors and patients decide when more aggressive treatments might be appropriate.
There's more on estrogen receptors at the U.S. National Cancer Institute.
SOURCES: Caroline Ford, Ph.D., department of cell and experimental pathology, Lund University, Malmo, Sweden; Minetta Liu, M.D., translational researcher/breast oncologist, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, D.C.; Feb. 23-27, 2009, Proceedings of the National Academy of Sciences
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