TUESDAY, June 3, 2003 (HealthDayNews) -- Significantly lower doses of the drug tamoxifen may be just as effective as the standard higher dose in fighting breast cancer, but with fewer side effects.
That's the insight out of a pilot study appearing in the June 4 issue of the Journal of the National Cancer Institute. The study did not measure the actual incidence of breast cancer, but measured a biomarker, a biochemical change, associated with the disease.
"We don't know if that marker means the same thing as preventing breast cancer," says Dr. Jay Brooks, chief of hematology/oncology at the Ochsner Clinic Foundation in Baton Rouge, La., who was not involved with the study.
"Tamoxifen is an incredibly great medicine that has very few side effects and before we start to mess with it, we've got to be sure that we're doing the right thing," Brooks adds.
That opinion seems to represent a consensus: Don't change standard tamoxifen dosing practice, but do initiate some new studies.
Tamoxifen is the standard therapy for premenopausal women who have estrogen receptor (ER) positive breast cancer, is also useful for many postmenopausal women with the same type of breast cancer, and is the only approved drug for healthy women who may be susceptible to the disease.
But the drug, which prevents estrogen from binding with breast cancer cells, does carry side effects, namely an increased risk of uterine cancer and blood clots, experts say.
"Right now, tamoxifen is the most effective drug for the treatment of breast cancer we have. That said, it does have toxicities that people are interested in avoiding," says Dr. Powel Brown, author of an accompanying editorial in the same issue of the journal.
Given those toxicities, there is a "highly concerted effort in trying to find agents that are superior to tamoxifen," adds Brown, an associate professor of medicine and molecular and cellular biology at Baylor College of Medicine in Houston.
One strategy has been to develop a better selective estrogen receptor modulator (SERM) than tamoxifen.
"That means a better drug similar to tamoxifen that doesn't have tamoxifen's bad side effects," Brown says.
A second strategy is to develop drugs that would lower the body's level of estrogen instead of blocking the estrogen receptors' activity.
A class of drugs called aromatase inhibitors does just that. Many drugs within this class have been approved and many are superior to tamoxifen for certain patients. Just this month, researchers announced that the aromatase inhibitor Femara, or letrozole, had higher one- and two-year survival rates than tamoxifen in women with locally advanced breast cancer. Results of the trial were published in the June 1 issue of the Journal of Clinical Oncology.
A third possible strategy would be to use existing tamoxifen in a different way, hence the current pilot trial using reduced levels of the drug.
The authors of the new study randomly assigned 120 women with ER-positive breast cancer to receive either 1 milligram, 5 milligrams or 20 milligrams a day of tamoxifen for four weeks. Then they measured levels of Ki-67, a tumor cell proliferation marker.
At the end of the treatment, production of Ki-67 decreased by an average of 15 percent in all three groups, compared with a reduction of 12.8 percent in control groups.
The results are intriguing, but not conclusive, researchers say.
"In terms of the dosage of tamoxifen, I would not change what doctors do. But this is really the first evidence that there's some suggestion that indeed low-dose tamoxifen might be efficacious and might have reduced side effects," Brown says.
But tamoxifen at its current dose still has a solid place in breast cancer treatment, he says.
"The aromatase inhibitors can only be used in postmenopausal women, not in premenopausal women, so tamoxifen is still our standard of treatment in that group," Brown says. "In addition, tamoxifen is the only approved drug for the reduction of risk of breast cancer in women who don't have it already."
Low-dose tamoxifen theoretically could be used in premenopausal women with breast cancer or for the potential prevention of breast cancer in those who don't have it, Brown adds.
All this points to the continuing individualization of breast cancer treatments, experts say.
"It's very encouraging but you've got to be a little cautious because you want that bottom-line result -- patients living longer or better -- before you wholeheartedly go over to something new," says Dr. Giuseppe Del Priore, an associate professor of obstetrics and gynecology at New York University School of Medicine.
"Most people take standard therapy, but individualization is on the horizon," he adds.
More information
The Susan G. Komen Breast Cancer Foundation and the National Cancer Institute have information on tamoxifen.
