Abstract PO4-01-12: Efficacy of neoadjuvant dose-dense versus standard chemotherapy regimens in ER+ HER2-negative breast cancer: a single-center matched-cohort study. Exploratory analysis of immune markers
Authors: Elena Kovalenko, Elena Artamonova, Yaroslav Zhulikov, Maxim Khoroshilov, Alexander Petrovskiy, Igor Vorotnikov, Tatiana Zabotina, Zaira Kadagidze
Journal: Cancer Research (2024)

Abstract Introduction: Dose-dense adjuvant CT improves long-term outcomes, which has been proved in clinical trials and meta-analysis. However, the efficiency of thе modern dose dence (dd) anthracycline-taxane (A-T) sequential regimens in the neoadjuvant (NA) setting of ER+HER2- breast cancer (BC) has not been assessed. Tumour-infiltrating lymphocytes (TILs) play a key role in the formation of anti-tumor immunity and can be one of the markers of treatment efficacy and prognosis. Studies evaluating TILs in ER+ BC have mixed results. Materials and methods. The aim of the study was to assess the rate of RCB 0-I of 4xddAC (doxorubicine/cyclophosphamide)–T (4xdocetaxel once every 3 weeks or 12xpaclitaxel weekly) NA chemo compared to standart regimen and to study the subpopulation composition of the lymphoid infiltrate and its effect on achieving RCB 0-I. RCB 0-I as a primary end point was chosen due comparable long-term results in ER+HER2- BC as per meta-analisys. Results: The study included pts with stage II-III ER+(ER≥10%) HER2- BC who received NA A-T chemo in a single center from Jan 2017 to Aug 2022. The majority of patients (85,2%) had stage III disease. Statistical hypothesis: NA ddAC–T chemo would increase the rate of RCB 0-1 to 32% from 22% with ACq3w (once every 3 weeks)-T, with a study power of 80%, ά = 0.05, 138 patients should be included in the study. A total of 315 patients were included, 147 received ddAC-T and 168 - ACq3w-T. After propensity matching analysis 138 patients in each group were included in the final analysis. TILs were studied in core-biopsy samples before NA chemo in 79 patients by flow cytometry. The following 8 subpopulations of lymphocytes were assessed as percentage in the cell pool: CD3+, CD3+CD4+, CD3+CD8+, CD4+CD127+CD25+, CD3-CD19+, CD3-CD16+CD56+, CD3+CD16+CD5+, CD8+CD279+(PD-1). The results are presented in medians (Me) due to abnormal distribution. The RCB 0 rate was 18.8% in the ddAC-T group vs 14.5% in the ACq3w-T group (p=0.379), RCB 0-1 - 33.3% vs 21.7% respectively (p=0.04). According to subgroup analysis, significant benefit of ddAC regimen found in patients ≤ 50 y.o., cN0, with PR ≥20%. For the following populations of TILs significant differences in Me for RCB0-I vs RCB II-III were observed: CD3+CD8+, CD3–CD19+, CD3–CD19+, CD8+CD279+. In multivariative analisys CD8+CD279+(PD-1)≤Me proved to be an independent predictive factor for RCB 0-I (p=0,048). Immunological signature CD8+CD279+ ≤ Me, CD3+CD8+ ≤ Me, CD4+CD25+ &amp;gt; Me, CD3-CD19+ &amp;gt; Me was associated with the rate of 66,7% of RCB 0-I vs 0% with the signature with the opposite values. Conclusion: ddAC-T NA chemo compared to standart regimen in ER+HER2- BC increases RCB0-1 rate. CD8+CD279+(PD-1)≤Me is an independent predictive factor for RCB 0-I. Citation Format: Elena Kovalenko, Elena Artamonova, Yaroslav Zhulikov, Maxim Khoroshilov, Alexander Petrovskiy, Igor Vorotnikov, Tatiana Zabotina, Zaira Kadagidze. Efficacy of neoadjuvant dose-dense versus standard chemotherapy regimens in ER+ HER2-negative breast cancer: a single-center matched-cohort study. Exploratory analysis of immune markers [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-01-12.