A number of genetic tests are available for breast cancer-related genes, and recent news suggests another test could predict responses to tamoxifen. More than 210,000 women in the United States will develop breast cancer. Approximately 70 percent of these cancers are fueled by estrogen, many of which are treated with tamoxifen, a drug designed to block the effects of estrogen in breast tissue. Some women take tamoxifen as a preventative measure against breast cancer.
An enzyme known as CYP2D6 is “responsible for activating tamoxifen to a metabolite called endoxifen that is nearly 100 times more potent as an anti-estrogen than tamoxifen itself,” says James Rae, PhD, research assistant professor of internal medicine at the University of Michigan Medical School. A study of 256 women with breast cancer “suggests that women who inherit a genetic variant in the CYP2D6 gene appear to be at higher risk of relapse when treated with five years of tamoxifen.” Women with this genetic variant (about 10 percent of women) were almost twice as likely to see their breast cancer return.
As always, further studies are needed, but researchers hope this finding may lead to a genetic test--not currently offered clinically. Research is being conducted by the members of the Pharmacogenetics Research Network to confirm whether genetic testing can be used to identify patients likely to respond to endocrine therapy, including tamoxifen. This group is led by David A Flockhart, MD, PhD at Indiana University School of Medicine.
One interesting sidenote in the study was that researchers also found that women with the CYP2D6 variant were less likely to have hot flashes. Any hot flashes among this group tended to be less severe, suggesting that this side effect could predict the gene variation. Ironically, Paxil--a selective serotonin reuptake inhibitors or SSRI used to treat hot flashes--can prevent tamoxifen from being activated. Effexor, another SSRI, does not interfere with tamoxifen’s activation. So, women with breast cancer and hot flashes or depression (SSRIs are also used to treat depression) might be well-advised to confer with their physician on possible drug interactions.
Their findings are published in the Dec. 20 issue of The Journal of Clinical Oncology and were reported by Breast Cancer News online (31 Dec 2005).
Marie Godfrey, PhD