New analyses of data from 2 large trials have found no association between the CYP2D6 genotype and the effectiveness of tamoxifen in preventing breast cancer recurrence, in contrast to several previous positive studies.
The new findings come from retrospective analyses of 2 huge trials — the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial comparing tamoxifen and anastrozole, and the Breast International Group (BIG) 1-98 trial comparing tamoxifen and letrozole.
They were presented at the 33rd Annual San Antonio Breast Cancer Symposium (SABCS): Abstracts S1-7 and S1-8. Presented December 9, 2010.
The fact that both studies were negative led experts to recommend that CYP2D6 testing not be used routinely to decide whether or not to prescribe tamoxifen.
Even the strongest proponent of this approach, Matthew Goetz, MD, from the Mayo Clinic in Rochester, Minnesota, who led the original studies showing an association, concedes.
Although criticizing some aspects of the new analyses in a discussion after the presentation, he concluded that physicians should not routinely test for CYP2D6 status before deciding whether to prescribe tamoxifen or an aromatase inhibitor, an approach that he had been advocating until now.
"We should stop offering these tests outside of clinical trials," Edith Perez, MD, from the Mayo Clinic in Jacksonville, Florida, told Medscape Medical News.
The rationale behind CYP2D6 testing is that women who have an inherited deficiency of this gene are poor metabolizers of tamoxifen, and have lower levels of the active metabolite endoxifen. In previous positive studies, including those by Dr. Goetz and colleagues, these poor metabolizers have shown less benefit from tamoxifen and higher rates of breast cancer recurrence.
This has always been a controversial area. To date, there have been 14 separate studies that have shown this association; however, 15 other studies have not found this effect, Dr. Goetz told the meeting.
http://www.medscape.com/viewarticle/734021?src=ptalk