No Side Effects from Tamoxifen (Nolvadex)? Why It May Not Be Working

Health Professional

Research on the possibility of a drug interaction between tamoxifen (nolvadex) and serotonin reuptake inhibitors (SSRIs) - a class of drugs that includes Paxil (paroxetine) and Prozac (fluoxetine hydrochloride) - has revealed an unexpected wrinkle: A significant number of women possess a genetic trait that inhibits the benefits of tamoxifen, regardless of whether they take Paxil or other drugs.

Women with the trait are unable to produce an enzyme known as CYP2D6, which is needed for the liver to convert tamoxifen into its active form, endoxifen. Endoxifen is far more potent than tamoxifen and is believed to be the key to how tamoxifen prevents the recurrence of breast cancer.

While this genetic trait can be present in women of any ethnicity, the trait is particularly common in women of Caucasian ancestry, with populations of women of German heritage showing prevalence rates as high as 10 percent for the gene. African-Americans and Hispanics appear to have much lower frequency of this gene, with rates around three percent. Interestingly, while the gene is extremely rare in Asians, being present in less than one percent of this group, about a quarter of Asians have a different genetic tendency that leads to reduced levels of CYP2D6 without inhibiting it entirely.

While genetic testing to determine if one has this trait is not yet standard practice, it is becoming increasingly common. At the Mayo Clinic in Rochester, Minn., oncologist Dr. Matthew Goetz routinely tests postmenopausal women who are candidates for tamoxifen. Those who possess the trait are usually put on an alternate course of treatment, such as Arimidex or aromatase inhibitors.

There are fewer alternatives available for premenopausal women, and since tamoxifene therapy may be preferable to none at all, Dr. Goetz does not necessarily recommend testing for women in their younger years.

One indication that a woman may have the trait, ironically, is an absence of negative side effects -- such as hot flashes - while taking tamoxifen. While a complete absence of side effects is generally hailed as good news, it could be an indicator that the treatment is simply not working, and is worth discussing with a physician.

According to Dr. Goetz, an FDA subcommittee has recommended including a discussion of this genetic effect in tamoxifen's labeling information.