Mayo researchers unlock mystery of breast cancer drugby Sea Stachura, Minnesota Public Radio
Researchers at the Mayo Clinic say they've discovered why the breast cancer drug Tamoxifen is effective. And in doing so, they've found why the drug does not work in some women. Tamoxifen is prescribed to tens of thousands of women each year. The researchers say their discovery could allow them to develop drugs for women whose cancers don't respond to tamoxifen.
Rochester, Minn. — Tamoxifen is the most common breast cancer drug around. It's designed to treat one type of the disease -- estrogen-receptor positive breast cancer -- which makes up about 80 percent of all breast cancers.
Tamoxifen doesn't work to treat all cancers, and doctors wanted to understand why.
A few years ago, Mayo Clinic researchers discovered that women whose bodies could metabolize tamoxifen into two substances called metabolites did well on the drug. One of those metabolites is called endoxifen.
Until now, doctors didn't know which metabolite actually treated breast cancer. Now they do.
"Those individuals who produce high levels of endoxifen from their tamoxifen therapy do quite well," said Mayo researcher John Hawse. "Whereas those individuals who produce very low levels of endoxifen do not."
Hawse conducted the lab study that tested each metabolite. Hawse says genetics determine how well a woman can metabolize tamoxifen into endoxifen, and that has implications for treatment.
"So we need to genotype patients to determine if they are going to be able to make endoxifen from their tamoxifen therapy," said Hawse. "If they cannot make endoxifen based on mutations in their gene, they are probably going to be very good candidates for an alternative therapy, because tamoxifen is likely to not work."
Hawse says those patients for whom tamoxifen doesn't work could be given the metabolite endoxifen directly.
Dr. P.J. Flynn treats patients at Minnesota Oncology and Hematology in the Twin Cities?. He says the research is interesting, but at this point, doesn't automatically translate into treatment for breast cancer patients.
"The human body is not the same as what happens in a test tube of cancer cells. There are many other things going on," said Flynn. "Other than it's interesting findings in their lab, it doesn't really tell me how to treat patients."
But the University of Minnesota's Dr. Carolyn Torkelson is excited by the research. She says it works with the medicine already being used by doctors. That means its lab findings are more likely to be borne out in clinical studies.
Torkelson says tamoxifen is a pro-drug, meaning the body has to break it down before it is effective.
"Why give somebody a pro-drug, if it's possible to give the product that is best utilized by the body to fight cancer?" Torkelson said.
The Mayo research is under review by a major scientific journal. Researchers presented it today at the San Antonio Breast Cancer Symposium.
Hawse and other Mayo doctors say this research could lead to many more revolutionary changes in treatments for breast cancer.
- All Things Considered, 12/11/2008, 4:49 p.m.