Controlled trial of tamoxifen as adjuvant agent in management of early breast cancer. Interim analysis at four years by Nolvadex Adjuvant Trial Organisation

Abstract

Tamoxifen ('Nolvadex'), an anti-oestrogen, has been evaluated as an adjunct to the local treatment of early breast cancer in a prospective randomised clinical trial. 1285 women (with pathological stage II premenopausal and pathological stage I and II postmenopausal disease) were treated by total mastectomy with either axillary node clearance or axillary node sampling and then randomised to receive either tamoxifen 10 mg twice daily for two years or no further treatment. Treatment failure (recurrent disease or death) at 21 months was reduced in patients receiving tamoxifen (14 X 2%) compared with controls (20 X 5%) (p = 0 X 01). This is equivalent to a prolongation of the disease-free interval from 21 months to 30 months at the mean follow-up time of 21 months. Subgroup analyses by menopausal, axillary lymph node, and oestrogen receptor status did not reveal a significantly different treatment effect in any of these subgroups. There has been no significant effect on mortality at this point in the study. This endocrine adjuvant therapy was well tolerated and treatment was discontinued in only 14 (2 X 2%) patients as a direct result of side-effects. Thus, tamoxifen significantly delays recurrence in early breast cancer. The magnitude of the effect is comparable with that associated with adjuvant cytotoxic chemotherapy at a similar follow-up time, but with minimal toxicity and excellent compliance.