UNC Clinical Trial Focuses on Finding the Right Tamoxifen Dose to Treat Breast Cancer

CHAPEL HILL, N.C. - A clinical trial funded by the University Cancer Research Fund and the Susan G. Komen for the Cure Foundation has enrolled its 500th and final participant. Women from 57 North Carolina counties and four states are taking part in a trial using individual genetic information to determine an effective dose of the drug, tamoxifen, used to treat breast cancer. View map.

Kirsten Rieth, a technical project manager at RTI International, was the 500th enrollee. “I decided to take part in the trial to help move the science forward,” she explains. Rieth has a background in science and at RTI is involved in moving research from the laboratory setting to commercial application.  “I believe that tailored treatment is the right way to go. People are all different, and medicines that work for some may not work for others.  This trial may help move us toward being able to prescribe the right medicine for each individual.”

William Irvin, MD, assistant professor of medicine and trial principal investigator says, “Both Dr. Howard McLeod and I were recruited to UNC with UCRF funding. We are glad to be able to offer this trial, also funded by the UCRF, to women across North Carolina.”

McLeod, PharmD, is the Eshelman Distinguished Professor in the UNC School of Pharmacy, and director of the UNC Institute for Pharmacogenomics and Individualized Therapy (IPIT).

Irvin explains, “With Dr. McLeod’s expertise in pharmacogenomics and Dr. Lisa Carey’s and my expertise in breast cancer, we were able to develop a trial that evaluates the impact of genotype-driven dosing of tamoxifen on drug concentrations in the blood and the impact of this strategy on patients’ quality of life. The UCRF funding allowed us to include a larger number of participants, thus giving more statistical significance to our results.

“The next steps for us to study will be the effect of other genetic differences in the body’s ability to metabolize tamoxifen and the whether genotype-driven dosing of tamoxifen helps improve breast cancer outcomes.”

Lisa Carey, MD, associate professor of medicine and medical director of the UNC Breast Center, and a mentor to Dr. Irvin, says, “The future of medicine lies in individualized therapy, which up to now has focused on characteristics of the tumor.  But we know that much of the time how well our drugs work has as much to do with the makeup of the person as with the makeup of the tumor.  This trial’s focus on matching the right dose to the right patient is how we all want to practice medicine.”

Irvin explains the science behind the study, “Tamoxifen is an excellent drug for personalized medicine, because there are already two FDA-approved doses, and we know a great deal about how it is metabolized.  The body has a gene that is responsible for converting tamoxifen to its active form.  There are several different versions of this gene; some are very active, some are less so.”

The study consisted of a blood draw that will allow UNC scientists to determine which of these genes an individual patient has.  If she has one of the less active versions of the gene, her tamoxifen dose will be increased to the higher FDA approved dose, and the after a few months, the active metabolite concentrations will be checked to see if changing the dose of tamoxifen can overcome having a less active form of the gene.”