Cytokines in the Management of High Risk or Advanced Breast Cancer: An Update and Expectation

A.      Carpi; A.      Nicolini; A.      Antonelli; P.      Ferrari; G.      Rossi

doi:10.2174/156800909790192392

Abstract

Some cytokines (interleukin (IL)-2, IL-11, transforming growth factor(TGF)β) stimulate, while others (IL-12, IL-18, Interferons (IFNs)) inhibit breast cancer proliferation and/or invasion. So far IL-2, IFNα, IFNβ and occasionally IFNγ, IL-6, IL-12 have been used for the treatment of advanced breast cancer either to induce or increase hormone sensitivity and/or to stimulate cellular immunity. Only two long term pilot studies suggest that IL-2 and IFNβ can improve clinical benefit and/or overall survival of metastatic breast cancer patients with minimal residual disease after chemotherapy or with disseminate disease non progressing during endocrine therapy. These results have been interpreted assuming that tumour microenvironment impairs the immune system of the host. Consequently, minimal disease or intense cytostatic effects following chemo or endocrine therapy, respectively, permit the patients immune system to respond to the stimulatory effect of the cytokines. Therefore a prospective, phase III, randomised, simple blind trial has been planned. The aim is to assess whether the addition of IFNβ and IL-2 to standard hormone therapy in postmenopausal patients with metastatic breast cancer and positive or unknown positive receptors prolongs the clinical benefit and survival since the metastatic diagnosis and the beginning of first line salvage antiestrogen therapy, compared with the results achieved with standard hormone therapy alone. If this immunotherapy prolongs survival of endocrine dependent metastatic breast cancer patients, IL-2 and IFNβ can also be evaluated as adjuvant treatment of patients with positive estrogen receptors.

Keywords: Cytokines, advanced breast cancer