The use of immunotherapy to treat metastatic breast cancer

March 19, 2018

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 (Fig 4). 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 [7] to 15.6 months [8] 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 [9]. 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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[1] Cheng Y. C.,Ueno N.T. Improvement of survival and prospect of cure in patients with metastatic breast cancer. Breast Cancer,2012, doi:10.1007/s12282-011-0276-3.

[2] 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.

[3] 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.

[4] 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.

[5] 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.

[6] 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.

[7] 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.

[8] 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.

[9] 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.

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