Andrea Nicolini*, Vivian Barak, Piermario Biava, Paola Ferrari, Giuseppe Rossi and Angelo Carpi Pages 941 - 962 ( 22 )
This article reviews the principal attempts of immune-modulation or immune therapy in metastatic breast cancer. It considers their rationale and reports on results from the relevant key clinical trials. Immune-modulatory or immune-stimulating cytokines used alone or combined with conventional therapies is among the principal approaches of immune manipulation in breast cancer. As this issue has recently been reviewed by us, the aim of the current article is to discuss our updated and unpublished data on this topic. Overall survival in luminal (28 patients) and non-luminal (9 patients) molecular subtypes is 91 and 59 months respectively that is about two and half or three times longer than expected. Thereafter, we focus on monoclonal antibodies (mAb) based-therapies including novel strategies to overcome resistance to anti-HER2 mAb. The main vaccine platforms in different molecular subtypes and immune therapies in triple negative metastatic breast cancer (m-TNBC) are discussed in the last sections. Some phase III investigations have already changed the current clinical practice. In fact, pertuzumab plus trastuzumab and docetaxel is the recommended first line regimen in HER2 positive locally recurrent or metastatic breast cancer and bevacizumab plus paclitaxel or docetaxel is a reasonable option for m-TNBC. In some other observational or phase I/II studies on first-line trastuzumab plus chemotherapy and hormonal therapy and in that on HER2 peptide/protein vaccines promising although preliminary findings have been reported to be further validated. In the remaining studies, results were disappointing. In the future, finding new predictive biomarkers and exploring more suitable synergizing combinations, time and dose-dependent-scheduled sequences of currently and further investigated immunological approaches are main challenges.
Immunotherapy, breast cancer, cytokines, mAb, m-TNBC, interferons.
Department of Oncology, Transplantations and New Technologies in Medicine, University of Pisa, Immunology Lab for tumor diagnosis, Hadassah University, Jerusalem, Scientific Institute of Research and Care Multimedica, Milan, Department of Oncology, Transplantations and New Technologies in Medicine, University of Pisa, Unit of Epidemiology and Biostatistics, Institute of Clinical Physiology, National Council of Research, Pisa, Department of Clinical and Experimental Medicine, University of Pisa