Some Women Get Less Benefit from Tamoxifen

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Cytochrome P450 2D6, or more commonly known as CYP2D6, is a metabolic enzyme that affects the breakdown of a wide range of drugs, including tamoxifen. Individual mutations that reduce activity of this certain gene have been shown to reduce the effectiveness of tamoxifen in women with a history of estrogen receptor-positive breast cancer. Interestingly, women with these same polymorphisms have been reported not to experience hot flashes, which are typically experienced by about 20 percent of women with the normal version of the gene.

In a recent letter to the Journal of Clinical Oncology, Bernardo Bonanni, MD, and colleagues reported data that confirmed the correlation of CYP2D6 polymorphism and the lack of response to tamoxifen therapy, although their data did show that women with CYP2D6 do experience hot flashes, contradicting a previous report.

In their presentation on CYP2D6 and breast cancer risk, Dr. Bonanni and colleagues reported on an expanded genotyping analysis of 182 patients taking tamoxifen for breast cancer prevention. The Italian trial results confirmed that there is a poor correlation between the polymorphism and tamoxifen efficacy, as significantly more women with CYP2D6 were diagnosed with breast cancer while receiving tamoxifen than those women who did not have the polymorphism.

These results suggest that CYP2D6 genotyping may be useful in identifying those patients at risk for recurrence who are most likely to benefit from tamoxifen