Abstract 129P
Background
We evaluated the impact of PAM50 molecular subtypes and gene expression signatures on the pathological response to neoadjuvant chemotherapy followed by Nivolumab for patients with Luminal B-like breast cancer.
Methods
The GIADA trial enrolled 43 premenopausal patients with stage II-IIIA Luminal B-like breast cancer (HR+/HER2- and G3 or Ki67>20%) to receive 3 cycles of epirubicin/cyclophosphamide followed by 8 cycles of nivolumab and exemestane (+ triptorelin). The rate of pCR was 16.3%; baseline TILs were significantly associated with pCR (Dieci MV, ESMO 2020). PAM50 subtypes and gene expression signatures were analyzed by nCounter® (Breast Cancer 360® panel).
Results
PAM50 subtypes were as follows: LumB 56%, LumA 25%, Basal 19%. pCR rate was significantly higher for Basal (50%) as compared to other subtypes (LumA 9%, LumB 8%, p=0.017). Inflammatory and immune-related gene signatures were significantly increased in pCR patients, including signatures tracking cytotoxic cells, macrophages, IDO1, IFNγ, inflammatory chemokines, macrophages, PD-L1, PD-L2, TIGIT, and tumor inflammation signature (adjusted p<0.05 for all). There was a weak to moderate positive significant correlation of Basal subtype with each of these immune signatures and TILs (Pearson coefficients ranging from 0.319 to 0.606), suggesting a partial biological overlap only. In bivariate logistic regression analysis, TILs and Basal subtype were independently associated with pCR (p=0.010 and p=0.049). An integrated score of TILs and Basal subtype had an AUC of 0.95 (95%CI 0.89-1.00) to predict pCR. According to the optimal cut-off derived by ROC analysis, pCR rate was 58.3% vs 0% for high vs low score (p<0.001).
Conclusions
Molecular subtype and immunity contribute to determining the sensitivity of Luminal B-like tumors to neoadjuvant sequential chemotherapy and anti-PD-1. Integrated assessment of these biomarkers should be incorporated in clinical trials of combined immuno-chemotherapy for Luminal-like breast cancer patients.
Clinical trial identification
NCT04659551.
Editorial acknowledgement
Legal entity responsible for the study
Department of Surgery, Oncology and Gastroenterology - University of Padua (PI: Prof. PF Conte).
Funding
Bristol Myers Squibb funded the study and provided nivolumab for the study. The translational research was funded by Veneto Institute of Oncology IOV-IRCCS (5x per Mille grant to MVD); Fondazione AIRC under IG 2018 –ID. 21354 project – P.I. Rosato Antonio; 5 per Mille 2019 - ID. 22759 program – P.I. Piccolo Stefano, G.L. Rosato Antonio and Pierfranco Conte; BIOV19ROSATO from 5 per Mille 2019, Veneto Institute of Oncology IOV-IRCCS to AR, and the Ministry of Health-Alliance Against Cancer (MoH-ACC) project “Research project on CAR T cells for hematological malignancies and solid tumors” to AR.
Disclosure
M.V. Dieci: Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Other, Training: Pfizer; Financial Interests, Personal, Advisory Board: Eli Lilly. G. Griguolo: Financial Interests, Personal, Other, travel support: Pfizer; Financial Interests, Personal, Other, travel support: Amgen; Financial Interests, Personal, Other, travel support: Daiichi; Financial Interests, Personal, Other, travel support: Novartis. A. Musolino: Financial Interests, Personal, Other, travel support: Roche; Financial Interests, Personal, Other, travel support: Eisai; Financial Interests, Personal, Other, travel support: Eli Lilly; Financial Interests, Personal, Other, travel support: Macrogenics. S. Spazzapan: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Other, travel support: Pfizer; Financial Interests, Personal, Other, registration to congresses: Pfizer; Financial Interests, Personal, Invited Speaker: Gentili; Financial Interests, Personal, Other, travel support: Gentili; Financial Interests, Personal, Other, travel support: Roche; Financial Interests, Personal, Other, registration to congresses: Roche; Financial Interests, Personal, Other, travel support: Tesaro; Financial Interests, Personal, Other, registration to congresses: Tesaro; Financial Interests, Personal, Invited Speaker: Celgene; Financial Interests, Personal, Other, registration to congresses: Celgene; Financial Interests, Personal, Other, travel support: Celgene; Financial Interests, Personal, Invited Speaker: Pierre-Fabre; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: MSD. G. Magni: Financial Interests, Personal, Other, Consultant: Labomar. G.L. De Salvo: Financial Interests, Institutional, Other, grant supporting the activity of the data centre for GIADA trial: DiSCOG, University of Padua. V. Guarneri: Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Principal Investigator, Local PI: AstraZeneca; Financial Interests, Institutional, Principal Investigator, Local PI: BMS; Financial Interests, Institutional, Principal Investigator, Local PI: Eli Lilly; Financial Interests, Institutional, Principal Investigator, Local PI: MSD; Financial Interests, Institutional, Principal Investigator, Local PI: Novartis; Financial Interests, Institutional, Principal Investigator, Local PI: Roche; Financial Interests, Institutional, Principal Investigator, Local PI: Synton Biopharmaceuticals. P.F. Conte: Financial Interests, Personal, Advisory Board, outside this work: Novartis; Financial Interests, Personal, Advisory Board, outside this work: Eli Lilly; Financial Interests, Personal, Advisory Board, outside this work: AstraZeneca; Financial Interests, Personal, Advisory Board, outside this work: Tesaro; Financial Interests, Personal, Other, Honoraria: BMS; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Eli Lilly; Financial Interests, Institutional, Research Grant, outside this work: Novartis; Financial Interests, Institutional, Research Grant, outside this work: Roche; Financial Interests, Institutional, Research Grant, for the conduction of the GIADA trial: BMS; Financial Interests, Institutional, Research Grant, outside this work: erck-KGaA; Financial Interests, Institutional, Research Grant, outside this work: Italian Ministry of Health; Financial Interests, Institutional, Research Grant, outside this work: Veneto secretary; Financial Interests, Institutional, Research Grant: University of Padua. All other authors have declared no conflicts of interest.