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

Abstract

Some cytokines (interleukin (IL)-2, IL-11, transforming growth factor(TGF)beta) stimulate, while others (IL-12, IL-18, Interferons (IFNs)) inhibit breast cancer proliferation and/or invasion. So far IL-2, IFNalpha, IFNbeta and occasionally IFNgamma, 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 IFNbeta 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 patient's 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 IFNbeta 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 IFNbeta can also be evaluated as adjuvant treatment of patients with positive estrogen receptors.

A new pharmacological approach to gastrointestinal cancer at high risk of relapse based on maintenance of the cytostatic effect

“…Recently, many studies have described different mechanisms promoting tumor growth and/or immune escape [8]. In advanced breast cancer, consistent with these mechanisms, we have recently proposed an interpretative model of the relationship between the immune system and tumor cell biology [8,9]. Accordingly, in this model, in metastatic endocrine-dependent breast cancers, the autocrine loops and paracrine actions of cancer cells in the tumor microenvironment are downregulated with subsequent arrested tumor progression and immune inhibition due to the cytostatic action of the antiestrogens.…”

Role of interleukin-10 in breast cancer

“…Immunoregulatory cytokines are an important component of biological milieu associated with breast cancer [6]. Several cytokines including Interferon (IFN)-a, b, and c; Interleukin-2 (IL-2), IL-6, IL-8, IL-10, and tumor necrosis factor-a (TNF-a) are known to play important role in coordinated manner in breast carcinogenesis [7,8].…”

Multiple sclerosis and breast cancer

“…For example, an Israeli study reports that interferon beta (IFNβ), which has been approved for the treatment of MS since 1993 (and thus it was likely used by MS patients in our study) lowers the risk of BC in female patients [29]. Furthermore, recent studies also demonstrate that IFNβ has an import role in the BC pathology [30], and IFNβ is now considered as a possible intervention for BC [31]. Despite evident clinical relevance, epidemiological studies addressing the effect of MS treatments on BC are scarce and inconclusive [32].…”