Re: Randomized Trial of Two Versus Five Years of Adjuvant Tamoxifen for Postmenopausal Early Stage Breast Cancer

Extract

The Swedish Breast Cancer Cooperative Group ( 1 ) concludes that 5 years of adjuvant tamoxifen is more beneficial than 2 years in postmenopausal women with early stage, invasive breast cancer in the subgroup of patients who were estrogen receptor (ER) positive. However, there are several issues that arise that we would like to highlight.

The authors provide an estimate of the trial size based on 0.01 (two-sided) and a power of 80%. This specification required the observation of 630 “ any first events.” Despite this, a statistically significant survival benefit is claimed (P .03), implying the use of 0.05 here (and elsewhere) and an analysis based on only 464 deaths [Table 2 in ( 1 ) ] [Table 3 in ( 1 ) deaths total 413]. Thus, with so few deaths observed, it is far too early to draw firm conclusions about survival, especially as results at 10 years are quoted. For example, an absolute survival benefit of 6% is claimed at 10 years for patients who had 5 years of adjuvant tamoxifen compared with those who had 2 years of adjuvant tamoxifen, but a confidence interval will, almost certainly, include the possibility of 0% benefit. In any event, such a statement is conditional on being recurrence free after 2 years of therapy and therefore should be adjusted for this probability of surviving those years. Such a calculation may be affected by an imbalance in patient numbers (61 fewer patients who had 5 years of adjuvant tamoxifen compared with those who had 2 years of adjuvant therapy) from those centers that randomized from the start of therapy, and therefore it is essential to report the pattern of recurrencesin this period.