The anti-hormone therapy tamoxifen can reduce breast cancer recurrence by about half in women with hormone-sensitive breast cancer. But it works better in some women than others. Researchers are not sure why.
"We do know that some tumors are inherently resistant to tamoxifen because of tumor genetic changes," says Daniel L. Hertz, Pharm.D., Ph.D., an assistant professor in the University of Michigan College of Pharmacy and member of the U-M Comprehensive Cancer Center.
"These tumor have found pathways to overcome anti-estrogen treatment. But we also believe some patients may be less likely to benefit from tamoxifen or endocrine therapy because of their genetics," Hertz says.
One theory is that in some patients, tamoxifen is not activated to the more potent estrogen inhibitor endoxifen. Patients with low levels of endoxifen may have worse outcomes on tamoxifen.
A meta-analysis by the International Tamoxifen Pharmacogenetics Consortium points to genetic variants. Researchers found patients with certain variants on the gene CYP2D6 had worse survival. Later analyses of prospective clinical trials, however, did not find the same link.