Tamoxifen for Adjuvant Therapy

The largest group of women in the 1995 analysis included almost 37,000 women randomized in 55 trials, all of which were designed to look at whether tamoxifen was an active agent in the postoperative setting. Women who were randomized to tamoxifen were found to have a highly significant reduction in the annual risks of both recurrence and death compared with women who received no adjuvant tamoxifen. This was seen for women who were randomized to tamoxifen for a median duration of 1, 2 or 5 years.

This effect was most pronounced for women who received 5 years of adjuvant tamoxifen, with a reduction in the risk of recurrence of 42% (standard deviation [SD]) and a reduction in the risk of death of 22% (SD 4). A longer duration of tamoxifen is currently being explored; however, at the present time there are no data to suggest an advantage to more than 5 years of tamoxifen.

The dose of tamoxifen that was administered in most of these trials was 20-40 mg each day, and there was no evidence of a dose-response relationship within this range.

Most of the benefit of tamoxifen was noted for women with estrogen-receptor (ER)-positive tumors rather than for patients with ER-poor tumors (Table 8.1). After 5 years of tamoxifen, women with ER-positive tumors had a reduction in the risk of recurrence of 50% (SD 4), compared with a risk reduction of only 6% (SD 11) for women with ER-poor tumors.

Within this "receptor-poor" category, some of the receptors must have been low receptor-positive, which partially accounts for the small positive effect.

The benefits of tamoxifen were most significant in women with the highest estrogen-receptor expression (>100 fmol receptor per mg cytosol protein).

The 1995 analysis was the first overview to provide convincing evidence of a lack of a substantial benefit for the effect of tamoxifen in the ER-poor population, and the hormone-receptor measurement is considered an important determinant of the response to treatment. Although the number of women was small, patients with ER-negative and progesterone-receptor (PR)-positive tumors appeared to benefit from tamoxifen; therefore, this subgroup most likely represents a tamoxifen-responsive population.

The proportional benefits of tamoxifen are similar for women with both lymph node-positive and node-negative disease. The absolute benefits, however, from the use of tamoxifen are related to each woman's risk of recurrence. Women with lymph node-positive disease have a higher annual risk of recurrence and mortality from breast cancer and therefore derive a greater absolute benefit from the use of tamoxifen (Fig. 8.1).

Table 8.1. Benefits of adjuvant tamoxifen by hormone-receptor status and age