New Study Reveals Genotype that Causes SSRI Interference with Tamoxifen
In a follow-up to their late-2003 study showing that the selective serotonin uptake inhibitor (SSRI) paroxetine can decrease the metabolism and efficacy of tamoxifen, researchers have now pinpointed genotypes that are linked with this effect, as well as other SSRIs that cause the same result.
Their findings, published in the January 5 Journal of the National Cancer Institute (JNCI), come from 80 women newly diagnosed with breast cancer and starting tamoxifen treatment. Twenty-four in this group were also taking SSRIs - including paroxetine, fluoxetine, sertraline, citalopram, and venlafaxine.
Previous studies have shown that when tamoxifen is broken down, the resulting molecules are as much as 100 times more powerful at blocking estrogen receptors and thereby exerting a cancer-inhibitive effect. The keys to breaking it down, however, are enzymes in the cytochrome P (CYP) group, including CYP2D6, which can be blocked by some SSRIs.
After genotyping the women in this study, monitoring their medication history, and testing their blood for plasma levels of tamoxifen and its metabolites, the team found that nonfunctional polymorphisms in either one or both copies of CYP2D6 are associated with SSRI use and low tamoxifen activity. Compared with women with two functional copies of the gene, those with one nonfunctional copy showed a 45 percent lower plasma level of tamoxifen metabolites, and those with two nonfunctional copies had levels that were significantly lower. Read more
NCI Leadership: A Model for Success
Last week in this space I provided a general overview of how we are recasting NCI's leadership structure, creating a management team headed by four deputy directors with whom I will work to guide NCI and the national cancer program through the exciting and demanding times ahead. This week I would like to provide a little more detail about NCI's leadership structure, to give further insight into how we make the decisions that will enable researchers to continue to make discoveries that are improving cancer patients' lives every day.
While the deputy directors play a central role in integrating NCI's many components, the institute's division and center directors have full managerial and executive responsibility for their operational units. They manage the resources under their purview and are accountable for all initiatives and activities in their respective areas. Read more