Abstract 1776P
Background
Triple-negative breast cancer (TNBC) consists of biologically diverse subsets of cancer. Homologous recombination deficiency (HRD) and immune reactions are implicated in TNBC biology. JBCRG22 is a multicenter trial to examine response to neoadjuvant chemotherapy (NAC) according to HRD status in TNBC. The translational research investigated the clinical significance of immune microenvironment of TNBC in association with HRD, germline BRCA1/2 mutation (gBRCAm) and response to NAC.
Methods
Patients aged < 65 years with high HRD (Myriad) or gBRCAm were randomized to weekly paclitaxel + carboplatin (group A1) or eribulin (ERI) + carboplatin (group A2) followed by anthracycline. Patients aged < 65 years with low HRD, or aged ≥ 65 years without gBRCAm were randomized to ERI + cyclophosphamide (group B1) or ERI + capecitabine (group B2); non-responders to the first 4 cycles of the therapy received anthracycline. Pre-treatment biopsy specimens were stained by multiplexed fluorescent immunohistochemistry using antibodies against CD3 (clone SP7), CD4 (4B12), CD8 (4B11), CD204 (SRA-E5) and Foxp3 (D608R). Immune cells with specific phenotypes were counted per mm2 in cancer cell nests (CN) and stromal regions surrounding cancer nests (ST). Statistical analyses included t-test and logistic regression analysis.
Results
A total of 67 samples from 4 treatment groups were analyzed. The density of CD8+ cells was significantly higher in gBRCAm+ tissues than in gBRCAm- tissues in both CN and ST while no difference was observed by HRD status in any type of immune cells. Patients with pCR showed a higher density of CD4+ cells in ST in the whole population. Patients with pCR showed a trend toward a higher density of CD8+ or Foxp3+ cells in CN and ST in group A1 but a trend toward a lower density in group A2. In a multivariate analysis, the density of CD4+ cells in CN and ST was a significant predictor of pCR independent of age, chemotherapy dose, HRD status and treatment groups (p = 0.0057 for ST and 0.009 for CN).
Conclusions
gBRCAm was associated with a higher density of CD8+ cells. The density of CD4+ cells in CN and ST was a significant predictor of pCR independent of treatment groups.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Japan Breast Cancer Research Group.
Funding
Eisai Co., Ltd.
Disclosure
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. Kitano: Financial Interests, Personal and Institutional, Principal Investigator, Joint research fund, Contract research expanses (clinical trial), lecture fee, advisory board: Ono Pharmaceutical Company; Financial Interests, Personal and Institutional, Principal Investigator, Joint research fund, Contract research expanses (clinical trial), lecture fee, advisory board: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant, Joint research fund, advisory board: Daiichi Sankyo; Financial Interests, Personal and Institutional, Principal Investigator, Joint research fund, Contract research expanses (clinical trial), lecture fee, advisory board: Eisai; Financial Interests, Personal and Institutional, Principal Investigator, Joint research fund, Contract research expanses (clinical trial), lecture fee: Astellas; Financial Interests, Personal and Institutional, Research Grant, Joint research fund: Gilead Sciences; Financial Interests, Personal and Institutional, Principal Investigator, Joint research fund, advisory board: Regeneron; Financial Interests, Institutional, Research Grant: Takara Bio Inc.; Financial Interests, Personal and Institutional, Principal Investigator, Joint research fund, Contract research expanses (clinical trial), lecture fee, advisory board: MSD; Financial Interests, Personal and Institutional, Principal Investigator, Joint research fund, Contract research expanses (clinical trial), lecture fee, advisory board: Chugai; Financial Interests, Institutional, Research Grant, Joint research fund: PACT Pharma; Financial Interests, Personal, Advisory Board, Lecture fee, advisory board: AstraZeneca; Financial Interests, Personal, Invited Speaker, Lecture fee, advisory board: Pfizer; Financial Interests, Personal, Invited Speaker, Lecture fee: Sanofi; Financial Interests, Personal, Invited Speaker, Lecture fee: Taiho; Financial Interests, Personal, Invited Speaker, Lecture fee, advisory board: Novartis; Financial Interests, Personal, Advisory Board, Lecture fee, advisory board: Sumitomo Dainippon Pharma; Financial Interests, Personal, Invited Speaker, Lecture fee: Ayumi Pharmaceutical Corporation; Financial Interests, Personal, Advisory Board, Advisory board: Rakuten Medical; Financial Interests, Personal, Advisory Board, Lecture fee, Advisory Board: GSK; Financial Interests, Personal, Expert Testimony, Comment fee: PMDA (Pharmaceuticals and Medical Devices Agency); Financial Interests, Personal, Advisory Board, Scientific Advisor: ImmuniT research Inc. 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; Non-Financial Interests, Personal, Member of the Board of Directors: Japanese Breast Cancer Society (JBCS); Non-Financial Interests, Personal, Member of the Board of Directors: Japan Breast Cancer Research Group Association (JBCRG). H. Bando: Financial Interests, Personal, Invited Speaker: Eizai 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; Financial Interests, Personal, Invited Speaker: DaiichiSankyo; 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. Ohtani: Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Pfizer. S. Nagai: Financial Interests, Personal and Institutional, Invited Speaker: Lilly; Financial Interests, Personal and Institutional, Invited Speaker: pfizer; Financial Interests, Personal and Institutional, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: Eisai. T. Nakayama: Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Pfizer. M. Takahashi: Financial Interests, Personal, Speaker’s Bureau: Eisai; Financial Interests, Personal, Speaker’s Bureau: Chugai. S. Saji: Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: Astra Zeneca; Financial Interests, Personal, Invited Speaker: Kyowa Kirin; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Taiho; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Institutional, Research Grant: Taiho; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Chugai; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Principal Investigator: MSD; Financial Interests, Institutional, Principal Investigator: Daiichi Sankyo; Financial Interests, Institutional, Principal Investigator: Chugai; Financial Interests, Institutional, Principal Investigator: AstraZeneca; Non-Financial Interests, Personal, Member of the Board of Directors: Japanese Breast Cancer Society; Non-Financial Interests, Personal, Member of the Board of Directors: Japanse Society of Medical Oncology; Non-Financial Interests, Personal, Member of the Board of Directors: Japan Breast Cancer Research Group. K. Aogi: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical; Financial Interests, Personal, Invited Speaker: Eisai Co., Ltd.; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical; Financial Interests, Personal, Invited Speaker: Novartis Pharma; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Mochida Pharmaceutical; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker: Eli Lilly Japan; Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Takeda Pharmaceutical. K. Kawaguchi: Financial Interests, Institutional, Research Grant: Eli Lilly; Financial Interests, Institutional, Research Grant: KBCRN; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical. 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. 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. M. Toi: Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Institutional, Research Grant: Chugai; 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; 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, Advisory Board: 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.