Genes Responsible for Cancer Drug Resistance

MINNEAPOLIS, Minn. -- Researchers have discovered a genetic difference that explains why some breast cancer patients don't respond to a drug that otherwise has been effective in keeping cancer from returning.

Tamoxifen has been credited with reducing by one-third the death rates of women with hormone-sensitive breast cancer, the most common type. Typically, premenopausal women take the drug for five years after surgery.

But a study by Mayo Clinic oncologist Dr. Matthew Goetz and James Rae of the University of Michigan showed that women with a key genetic difference were almost twice as likely to experience breast cancer relapse.

In most women, tamoxifen becomes a powerful cancer-fighting agent. The drug interacts, or metabolizes, with a liver enzyme, making it an even more powerful chemical compound "that is nearly 100 times more potent than tamoxifen," Goetz said.

But some women have inherited a genetic change that lowers the levels of the liver enzyme in their bodies.

"We are really looking at the role of inheritance in the individual drug effect," Goetz said.

Goetz and other Mayo researchers hope to uncover more genetic differences to help physicians make more informed choices among treatment options.

Goetz's research suggests that another class of cancer-fighting drugs called aromatase inhibitors might be more effective for women who do not metabolize tamoxifen, an area that merits further research, he said.

The findings, released Friday, appear in the Dec. 20 issue of the Journal of Clinical Oncology.