Breast cancer, in the stage with distant metastases, is an incurable disease with a 5 years survival rate of about 5-10% (1). Immunotherapy has recently improved survival in metastatic breast cancer patients with breast cancer harbouring the expression of HER 2 receptor. Particularly in HER 2 positive patients pertuzumab plus trastuzumab and docetaxel is the recommended first line regimen and in triple negative breast cancer patients (TNBC) bevacizumab plus paclitaxel or docetaxel is a reasonable option. In the metastatic breast cancer patients responding to conventional antiestrogens without or with HER 2 receptor, the addition of interferon beta-interleukin 2 sequence importantly prolongs quality and length of survival in a pilot study of 42 patients. In fact, in all patients median progression-free survival (PFS) from the beginning of hormone-therapy was 33 months, (Fig.1) and median OS 82 months (Fig 2); cumulative survival at 5 and 10 years±SE were 0.69±0.07 and 0.15±0.06 respectively. In the overall population these data confirm the previously reported findings (2-4). In the luminal sub-type, median PFS was 33 months (Fig.3) and median OS was 91 months (Fig 4). In the non-luminal sub-type, median PFS was 32 months and median OS was 59 months. Therefore, a relevant PFS and OS improvement occurred both in luminal and in non-luminal molecular subtypes compared with that expected in similar populations. In fact, equal or less than 10 months [5-6] is the reported median PFS in non-luminal breast cancer patients and it ranges from 11.2 months  to 15.6 months  in luminal patients. Moreover, 30.6 and 24.4 months have been reported as the best median OS in luminal and non-luminal breast cancer patients respectively . In some observational or phase I/II studies on HER 2 peptide/protein vaccines promising although preliminary findings have been reported.
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 Nicolini, A.; Carpi, A.; Ferrari, P.; Biava, P.M.; Rossi, G. Immunotherapy and Hormone-therapy in Metastatic Breast Cancer: A Review and an Update. Curr Drug Targets, 2016, 17 (10), 1127-1139.
 Nicolini, A.; Carpi, A. Beta-interferon and interleukin-2 prolong more than three times the survival of 26 consecutive endocrine dependent breast cancer patients with distant metastases: an exploratory trial. Biomed Pharmacother, 2005, 59 (5), 253-263.
 Nicolini, A.; Rossi, G.; Ferrari, P.; Carpi, A. Clinical and laboratory patterns during immune stimulation in hormone responsive metastatic breast cancer. Biomed Pharmacother, 2014, 68 (2), 171-178.
 Zhang, J.; Fan, M.; Xie, J.; Wang, Z.; Wang, B.; Zhang, S.; Wang, L.; Cao, J.; Tao, Z.; Li, T.; Hu, X. Chemotherapy of metastatic triple negative breast cancer: Experience of using platinum-based chemotherapy. Oncotarget, 2015, 6 (40),43135-43143.
 Fan, Y.; Xu, B.H.; Yuan, P.; Ma, F.; Wang, J.Y.; Ding, X.Y.; Zhang, P.; Li, Q.; Cai, R.G. Docetaxel-cisplatin might be superior to docetaxel-capecitabine in the first-line treatment of metastatic triple-negative breast cancer. Ann Oncol, 2013, 24 (5), 1219-1225.
 Lam, SW.; de Groot, S.M.; Honkoop, A.H.; Jager, A.; ten Tije, A.J.; Bos, M.M.; Linn, S.C.; van den Bosch, J.; Kroep, J.R.; Braun, J.J.; van Tinteren, H.; Boven, E.; Dutch Breast Cancer Research Group.. Paclitaxel and bevacizumab with or without capecitabine as first-line treatment for HER2-negative locally recurrent or metastatic breast cancer: a multicentre, open-label, randomised phase 2 trial. Eur J Cancer, 2014, 50 (18), 3077-3088.
 Dickler, M.N.; Barry, W.T.; Cirrincione, C.T.; Ellis, M.J.; Moynahan, M.E.; Innocenti, F.; Hurria, A.; Rugo, H.S.; Lake, D.E.; Hahn, O.; Schneider, B.P.; Tripathy, D.; Carey, L.A.; Winer, E.P.; Hudis, C.A. Phase III Trial Evaluating Letrozole As First-Line Endocrine Therapy With or Without Bevacizumab for the Treatment of Postmenopausal Women With Hormone Receptor-Positive Advanced-Stage Breast Cancer: CALGB 40503 (Alliance). J Clin Oncol, 2016, 34 (22), 2602-2609.
 Zielinski, C.; Láng, I.; Inbar, M.; Kahán, Z.; Greil, R.; Beslija, S.; Stemmer, S.M.; Zvirbule, Z.; Steger, G.G.; Melichar, B.; Pienkowski T.; Sirbu, D.; Petruzelka, L.; Eniu, A.; Nisenbaum, B.; Dank, M.; Anghel R.; Messinger, D.; Brodowicz, T; TURANDOT investigators. Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer (TURANDOT): primary endpoint results of a randomised, open-label, non-inferiority, phase 3 trial. Lancet Oncol, 2016, 17 (9), 1230-1239.