TAM-01 Finds Longer Tamoxifen Duration Is Not Better

SAN ANTONIO—Ten-year results from the TAM-01 trial indicate that maximal benefits of tamoxifen are achieved within 5 to 6 years of treatment, Thierry Delozier, MD, of the Centre Francois Baclesse, Caen, France, reported at the 28th Annual San Antonio Breast Cancer Symposium (abstract 14).

Between 1986 and 1995, the TAM-01 trial randomized more than 3,700 women with early breast cancer to either discontinue tamoxifen after 2 to 3 years (short-duration group) or to continue on the drug until recurrence, toxicity, or death (long-duration group). In 1997, the protocol was amended to limit tamoxifen to no more than 10 years after randomization. This provided a comparison between tamoxifen for 2 to 3 years vs 12 to 13 years. The patients were age 75 or younger; 69% were node-positive. Of those with known hormone-receptor status, 87% were positive. Median duration of follow-up was 111 months in the short-term group and 116 months in the long-duration group. Median tamoxifen duration at randomization was 27 months in both groups. Study results were updated in September 2005.

Overall survival did not differ between the two groups, but disease-free survival was significantly better in the long-duration group. Significant risk reductions in disease-free survival were observed in ER-positive and node-positive patients receiving long-term tamoxifen but not in women who were node negative. "The annual hazard ratio for short-term vs long-term showed a significant difference between the two groups," Dr. Delozier said. "But it was limited to the first years and significantly from year 1 to year 4." The annual recurrence rate was higher in the first years for patients who stopped tamoxifen but then decreased rapidly to the level of patients who continued to take the drug. During follow-up, second malignancies arose in 234 women on long-term tamoxifen and in 245 on short-term therapy. The incidence of endometrial cancer was only slightly higher in the long-term group—29 cancers vs 21 cancers. Contralateral breast cancer was slightly less common among women on long-term tamoxifen (51 vs 64).

He concluded that longer treatment is associated with a significant reduction in the risk of recurrence but offers no mortality advantage. Moreover, the recurrence benefit of long-term tamoxifen is transient. "The reduction decreased with time, and continuing tamoxifen after 5 or 6 years does not lead to a better recurrence reduction. So the optimal duration . . . is limited to 5 to 6 years," he said.