Abstract 1766P
Background
Inflammation of a tumor microenvironment comprises infiltrating immune cells and activated fibroblasts, which secrete cytokines, chemokines, and growth factors to which the tumor responds, especially in triple-negative phenotype in breast cancer. We have focused on the longitudinal analysis of cytokine profile in the peripheral blood in patients with operable triple-negative breast cancer and identified correlations between distinct immune phenotypes and clinical response.
Methods
Peripheral blood samples were collected from the JBCRG-22 trial, consisted of 4 arms of neoadjuvant chemotherapy: paclitaxel (A1) or eribulin (A2) plus carboplatin, followed by anthracycline, eribulin plus cyclophosphamide (B1), and eribulin plus capecitabine (B2). The cytokines in serum samples, IL-1β, IL-1γα, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-16 IL-17, IL-18, G-MCSF, IFN-γ, MCP-1, MIP-1α, MIP-1β, SCGF-β, PDGF-BB, RANTES, VEGF, bFGF and TNF-α were measured. Comprehensive statistical analysis was performed in order to evaluate the measured cytokine data using Python and the Jupyter notebook version 6.1.4.
Results
A total of 294 samples from 4 treatment groups and five-time points, before neoadjuvant chemotherapy, day 15 of cycle 1, during cycle 4, before surgery, and one year after surgery were analyzed. Longitudinal comprehensive correlation analysis of cytokines revealed responder group has a specific signature pattern, especially in IL-1β, IL-2, IL-16, IL-18, M-CFS, MIP1, and TNF-α at the baseline measurement and IL-12, FGF, IL-2, HGF, and SCGF-β in time series data. The correlation of each cytokine before chemotherapy was much stronger in the responder group than in the non-responder group (median correlation coefficient: 0.52 vs. 0.12, 95% CI: -0.43 to -0.37, p<0.0001).
Conclusions
Longitudinal analyses of cytokine profiles revealed systemic immune profile might be significant in predicting response to neoadjuvant chemotherapy in TNBC. Immune profiling using liquid biopsy should be required to predict and monitor the efficacy of chemotherapy, and further omics analysis is needed.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Japan Breast Cancer Research Group (JBCRG).
Funding
Eisai Co., Ltd.
Disclosure
K. Kawaguchi: Financial Interests, Institutional, Research Grant: Eli Lilly; Financial Interests, Institutional, Research Grant: KBCRN; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical; Financial Interests, Institutional, Research Grant: Astellas. N. Masuda: Financial Interests, Personal, Speaker’s Bureau: Chugai; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Eli-Lilly; Financial Interests, Institutional, Funding: Eisai; Financial Interests, Institutional, Funding: Takeda; Financial Interests, Institutional, Funding: Chugai; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: MSD; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: Eli-Lilly; Financial Interests, Institutional, Funding: Kyowa-Kirin; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Eisai,; Financial Interests, Institutional, Funding: Sanofi; Financial Interests, Institutional, Funding: Nihon-Kayaku ; Financial Interests, Institutional, Funding: Daiichi Sankyo; Financial Interests, Personal, Member of the Board of Directors: Japanese Breast Cancer Society (JBCS); Financial Interests, Personal, Member of the Board of Directors: Japan Breast Cancer Research Group Association (JBCRG). H. Bando: Financial Interests, Personal, Invited Speaker: Eisai Co., Ltd; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd. T. Yamanaka: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Eizai; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Kyowa-Kirin; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pfizer. S. Imoto: Financial Interests, Institutional, Research Grant: Eizai; Financial Interests, Institutional, Research Grant: Taiho; Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: KyowaKirin. N. Tamura: Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical; Financial Interests, Institutional, Research Grant: Eisai. T. Aruga: Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: AstraZeneca. M. Takada: Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Institutional, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Nippon Kayaku; Financial Interests, Personal, Invited Speaker: Kyowa Kirin; Financial Interests, Institutional, Invited Speaker: Yakult. T. Ueno: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd.; Financial Interests, Personal, Invited Speaker: Eisai Co., Ltd.; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Novartis Pharma K.K.; Financial Interests, Personal, Invited Speaker: Taiho. S. Ogawa: Financial Interests, Personal and Institutional, Advisory Role: Kan Research Institute, Inc.; Financial Interests, Personal and Institutional, Advisory Role: ChordiaTherapeutics, Inc.; Financial Interests, Personal, Stocks/Shares: Asahi Genomics Co., Ltd.; Financial Interests, Personal and Institutional, Funding: Sumitomo Dainippon Pharma Co., Ltd.; Financial Interests, Personal and Institutional, Funding: Otsuka Pharmaceutical Co., Ltd.; Financial Interests, Personal and Institutional, Funding: Eisai Co., Ltd.. S. Ohno: Financial Interests, Personal, Speaker’s Bureau: Chugai; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly; Financial Interests, Institutional, Sponsor/Funding: Taiho; Financial Interests, Institutional, Sponsor/Funding: Eisai. S. Morita: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca K.K.; Financial Interests, Personal, Speaker’s Bureau: Bristol-Myers Squibb Company; Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceutical Co. Ltd.; Financial Interests, Personal, Speaker’s Bureau: Eisai Co., Ltd.; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly Japan K.K; Financial Interests, Personal, Speaker’s Bureau: MSD K.K; Financial Interests, Personal, Speaker’s Bureau: Pfizer Japan Inc.; Financial Interests, Personal, Speaker’s Bureau: Taiho Pharmaceutical Co. Ltd. M. Toi: Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical Co., Ltd; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Institutional, Principal Investigator: Pfizer; Financial Interests, Institutional, Funding: Pfizer Japan Inc.; Financial Interests, Personal, Invited Speaker: Kyowa-Kirin; Financial Interests, Personal, Advisory Board: Kyowa-Kirin; Financial Interests, Institutional, Research Grant: Kyowa-Kirin; Financial Interests, Personal, Invited Speaker: Taiho; Financial Interests, Institutional, Research Grant: Taiho; Non-Financial Interests, Personal, Member of the Board of Directors: JBCRG Association; Financial Interests, Institutional, Research Grant: JBCRG Association; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Exact Science; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Konica Minolta; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Invited Speaker: Shimadzu; Financial Interests, Institutional, Research Grant: Shimadzu; Non-Financial Interests, Institutional, Member of the Board of Directors: KBCRN; Non-Financial Interests, Institutional, Member of the Board of Directors: OOTR; Financial Interests, Personal, Invited Speaker: Yakult; Financial Interests, Institutional, Research Grant: Yakult; Financial Interests, Personal, Invited Speaker: Nippon Kayaku; Financial Interests, Institutional, Research Grant: Nippon Kayaku; Financial Interests, Institutional, Research Grant: AFI technologies; Financial Interests, Personal, Advisory Board: Athenex Oncology; Financial Interests, Personal, Advisory Board: Bertis; Financial Interests, Personal, Advisory Board: Terumo; Financial Interests, Personal, Advisory Board: Luxonus; Financial Interests, Institutional, Research Grant: Luxonus; Financial Interests, Institutional, Research Grant: Shionogi; Financial Interests, Institutional, Research Grant: GL Science; Financial Interests, Personal, Advisory Board: Kansai Medical Net. All other authors have declared no conflicts of interest.