The role of endocrine therapy in primary breast cancer

A recent overview of the results of all trials of adjuvant chemotherapy suggests a clinically and statistically significant advantage for premenopausal women with positive axillary nodes. The results of the same approach for all other women with early breast cancer are very disappointing. These data suggest that contrary to the original hypothetical model, adjuvant chemotherapy is exerting its effect indirectly via chemical castration. In contrast, the results of trials of adjuvant tamoxifen have been more promising and, again, in contrast to the original premises, it would appear that a modest improvement in survival and delay in recurrence can be achieved amongst all groups of women independent of age, nodal status and oestrogen receptor content of the primary tumour. In order to explain these counter-intuitive observations, it is necessary to elaborate an alternative biological model. This paper describes the current thinking on the mode of action of the "anti-oestrogens" and the possible role of inhibitory growth factors activated indirectly by anti-oestrogens. Future trials of adjuvant systemic therapy for early breast cancer should include studies on the duration of tamoxifen, comparing 2 yr with longer, and a comparison of tamoxifen alone with polychemotherapy for premenopausal node positive patients.