Early Results Suggest Small Benefit of Longer Tamoxifen Therapy

December 17, 2007

Women with breast cancer who take adjuvant tamoxifen for 10 years have a lower risk of recurrence than their counterparts who take it for 5 years, although the difference is thus far small, according to early results of the ATLAS (Adjuvant Tamoxifen, Longer Against Shorter) trial presented at SABCS (abstract 48).

Women with breast cancer who take adjuvant tamoxifen for 10 years have a lower risk of recurrence than their counterparts who take it for 5 years, although the difference is thus far small, according to early results of the ATLAS (Adjuvant Tamoxifen, Longer Against Shorter) trial presented at SABCS (abstract 48).

Richard Peto, PhD
Photo Courtesy SABCS/Todd Buchanan 2007

"The question of how long to give tamoxifen has been around for more than 25 years now," said presenting author Richard Peto, PhD. The international trial randomized 11,500 women with treated breast cancer who had completed 5 years of tamoxifen therapy to either continue taking the drug for 5 more years or stop taking it. Estrogen receptor (ER) status was positive in 59% of the patients and untested in 41% (therefore, 90% were estimated to be ER-positive). Halfway through the trial, 83% in the longer-duration group were taking tamoxifen as were 4% in the shorter-duration group (therefore, 80% were compliant), Dr. Peto said. "When you combine these factors, ATLAS is getting an estimate of something like 72% of the true effect of 5 extra years of tamoxifen in ER-plus disease," he said. "That will be true for the benefits and for the side effects." With a mean follow-up since randomization of about 4.2 years per woman, Dr. Peto reported the annual rate of recurrence was 2.9% per year in the longer-duration group, compared with 3.4% per year in the shorter-duration group, a significant difference (ratio, 0.87). The respective annual rates of breast cancer mortality were 1.4% and 1.5% per year, a nonsignificant difference (ratio, 0.89). Turning to safety, Dr. Peto noted that endometrial cancer is more common with longer tamoxifen use but is seldom fatal. "We are preventing something like 100 breast cancer recurrences at the same time as causing something like 20 endometrial cancer cases," he said. He commented that earlier concerns that longer tamoxifen use may, in fact, increase the risk of recurrence were based only on interim findings of two smaller trials. Definitive ATLAS results will probably not be available until 2015, but obtaining these long-term outcomes is important, according to Dr. Peto. "The differences aren't enormous, but if there is a difference of a few percent in the 15-year recurrence risk or even the 20-year recurrence risk, then it's worth knowing about," he said. "The world in the future won't always involve tamoxifen. ... There will be ways of getting the therapeutic advantages of tamoxifen without the ... side effect disadvantages."

Disclosures:

The author(s) have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.