Abstract P1-14-19: Clinical and morphological results of neoadjuvant treatment with tumor necrosis factor-alpha-thymosin-alpha1 (TNF-T) of triple-negative locally advanced breast cancer patients
Authors: Vladimirova LY , Podzorova NA , Zlatnik EY , Nepomnyaschaya EM , Zakharova NP 
Published: May 2016

Abstract
Background. There is a few data on tumor necrosis factor drugs used in neoadjuvant treatment in locally advanced breast cancer (LABC) patients but there is a clinical need to increase the efficiency of standard therapy and to gain complete regression which is of great importance for survival. The aim of the study was to evaluate the efficacy of recombinant hybrid protein of tumor necrosis factor-alpha-thymosin-alpha1 (TNF-T) in neoadjuvant treatment of triple-negative LABC (TN LABC).
Methods. Eligibility criteria included TN LABC of IIB-IIIB stages, ECOG≤1, adequate liver, kidney and bone marrow function, no brain metastases. Recombinant hybrid protein of TNF-T 200000 IU was used peritumorally (injected around the tumor) on D1-5 (30 min before cytostatics injection), combined with standard FAC or PA regimens.
Results. 52 women were recruited between April 2012 – October 2013 (mean age 53.3±1.1 years). Group A (20 pts) received recombinant hybrid protein of TNF-T combined to PA (11) and FAC (9) up to 6 courses. Group B (32pts) received standard PA (18) and FAC (14). Tumor response (TR) in Group A was 80% and in Group B 71.9% (p&lt;0.05), including CR 15% and 6.25% correspondingly (p&lt;0.05). After neoadjuvant chemotherapy quantity of CD3+CD8+ cells in group A (PA) was significantly higher than in group B (PA) (31.5±2.8% and 21.7±2.25% correspondingly, p&lt;0.05). Content of B-lymphocytes (CD20) decreased during the treatment in group B (from 15.5±0.53% to 13.7±0.55% (FAC) and from 16.7±0.97% to 12.7±1.0% (PA) correspondingly, p&lt;0.05). CD20 level in group A after the treatment PA+TNF-T was 15,0±1,0%, after FAC+TNF-T was 15,4±1,4% which were different significantly from those in group B (p&lt;0.05). Common toxicities in Group A were: neutropenia Gr1 – 15.9% courses, nausea and vomiting Gr2– 27.2%, polyneuropathy Gr1/2 – 9%. TNF-T-specified toxicities were: hyperthermia Gr1 – 45.4%; local reaction (aula, pain) Gr1 lasted for 24-48 hrs – 90.9%. Group B: neutropenia Gr 1/2 – 21.2%, nausea and vomiting Gr2– 32.5%, polyneuropathy Gr1/2 – 10,6%, diarrhea Gr1 – 4,5. All patients in Group A were operated successfully, no postoperative complications connected with recombinant hybrid protein of TNF-T use were observed. By the time of abstract submission OS in Group A was 28.4±1.1mos, in Group B was 26.1±1.4mos; EFS in Group A was 26.9±1.3mos, in Group B was 22.9±1.2mos (p&lt;0.05).
Conclusions. TNF-T injected peritumorally is well-tolerated and allows to enhance an antitumor effect of cytostatics (pCR) which is of great importance for survival in TN LABC. The proposed method of the locally application of recombinant hybrid protein of TNF-T has mainly immunostimulant effect on CD3+CD8+ in patients with PA regimen. Recombinant TNF-T with PA and FAC has protected B-cell component of the immune system from immunosuppressive effect as well.
Citation Format: Vladimirova LY, Podzorova NA, Zlatnik EY, Nepomnyaschaya EM, Zakharova NP. Clinical and morphological results of neoadjuvant treatment with tumor necrosis factor-alpha-thymosin-alpha1 (TNF-T) of triple-negative locally advanced breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-14-19.