The effect of adjuvant tamoxifen: The latest results from the Cancer Research Campaign adjuvant breast trial

Abstract

The CRC Adjuvant Breast Trial, launched in 1980 to repeat both the Nolvadex Adjuvant Trial Organisation tamoxifen trial and the Scandinavian trial of perioperative cyclophosphamide trial, randomised 2230 stage I or II early breast cancer patients in a 2 × 2 factorial design to investigate the benefits of a short course of perioperative cyclophosphamide or tamoxifen daily for 2 years. At a median follow-up of 7.8 years, no significant benefit is noted for perioperative cyclophosphamide, however the main effect analysis for adjuvant tamoxifen demonstrates a significant improvement in disease-free survival which increases with time over the follow-up period. These results are in keeping with the World Overview of Trials of Adjuvant Tamoxifen. However, this study is unique, having a large number of node negative patients and over 500 premenopausal women in a comparison of tamoxifen and control. The relative risk reductions for the node negative patients for disease-free survival are greater than for node positive patients. This might suggest that the absolute benefit for adjuvant tamoxifen is similar in both groups of patients, bearing in mind the increase risk of relapse with node positive patients. No trend for interaction emerges according to age or menopausal status suggesting an identical benefit for pre and postmenopausal women. Similar relative risk reductions are seen when the data are stratified according to tumour size, suggesting a similar positive benefit may be seen for all patients irrespective of tumour size. Of particular interest is the incidence of contralateral breast cancer, the initial overall effect which emerged at the third year of follow-up ceases to be apparent. However subgroup analysis according to menopausal status suggests a trend for interaction with a reduction in the risk of contralateral breast cancer in the postmenopausal women and a marginal increase in the risk of contralateral breast cancer in premenopausal women. Plausible mechanisms exist to explain this difference in outcome and these data need to be confirmed or refuted by other large trials of adjuvant tamoxifen especially at this time when the chemoprophylaxis of breast cancer in high risk premenopausal women by tamoxifen is being considered.