Gene Test Might Predict Tamoxifen's Effectiveness

Oct. 7 -- TUESDAY, Oct. 6 (HealthDay News) -- A genetic variant seems to predict resistance to the breast cancer drug tamoxifen, German researchers report.

The findings, which appear in the Oct. 7 issue of the Journal of the American Medical Association, could allow clinicians to predict which women will benefit most from the drug, which has been the gold standard of breast cancer care for the past 25 years. Women who do carry the gene variant may be candidates for alternative treatments.

The gene affects the activity of the CYP2D6 enzyme, which converts tamoxifen into its metabolite, endoxifen. It is this metabolite that allows the drug to work its magic against breast tumors.

"This is really the largest study that's been done in this area," noted V. Craig Jordan, scientific director of Georgetown Lombardi Comprehensive Cancer Center in Washington, D.C. "It's now clear if you don't have the ability to create endoxifen out of tamoxifen, you don't have a good response rate. This is really important because for women who are taking the drug for five years, you better know it's going to work for you."

And for women who won't have the desired therapeutic response to tamoxifen, there are now other options, namely in the form of medicines called aromatase inhibitors, which, like their older cousin tamoxifen, inhibit the effect of estrogen on cancer.

"In postmenopausal women, if you've got this aberration in your metabolism of tamoxifen, you could be offered an aromatase inhibitor, so there is something one could do for a person at this particular point," Jordan said.

Jordan is known as the "father of tamoxifen" because he helped develop the drug.

On the other hand, if your body is able to metabolize tamoxifen effectively, Jordan added, "it's as good a therapy as you can get."

Although tamoxifen has an excellent track record, many women do develop resistance to the drug. And researchers are in the process of calibrating when tamoxifen might be more appropriate to a situation and when aromatase inhibitors would better serve the patient.