Interferon plus tamoxifen treatment for advanced breast cancer: in vivo biologic effects of two growth modulators

Abstract

The effects of interferon-alpha (IFN) plus tamoxifen (TMX) in the treatment of advanced breast cancer were assessed. Changes of in vivo biologic determinants including hormone receptors, P24 protein, Ki-67 and growth factor expression were evaluated. Seven patients with advanced, heavily pretreated, breast cancer with accessible disease, underwent biopsy prior to and after sequential treatment with IFN and IFN plus TMX. Clinically 4/7 patients responded to treatment with one complete and three partial remissions. Apart from the favourable response rate the sequential in vivo changes in expression of tumour variables were of considerable interest. IFN treatment consistently increased the expression of the estrogen receptor (ER) and of the estrogen regulated protein P24 while decreasing the expression of the proliferation associated antigen Ki-67. Addition of TMX on the other hand resulted in a reduction of ER expression to pre-IFN levels and a rise in progesterone receptor (PR) expression. When the effect of either IFN or IFN plus TMX on the expression of two growth factors was assessed they were found to be somewhat variable. While PDGF expression tended to be suppressed, there was no clinical correlation with response to therapy. TGF beta expression was found in all patients prior to treatment and while all non-responders showed reduction of TGF beta following treatment, the alterations were variable amongst responders (including two patients with increased expression, one with no change, and one with decreased expression). It is concluded that both IFN and TMX exert multiple effects on the expression of tumour biologic variables and that while the study confirmed some of the predictions from in vitro models, the in vivo effect are more complex than has been appreciated from the models. From the clinical point of view, it might be expected that treatment which enhances the expression of ER in tumours should have a positive effect on the response to TMX.