242MO - Association of tumor-infiltrating lymphocytes (TILs) with recurrence score (RS) in patients with hormone receptor-positive (HR+)/HER2-negative (HER2-) early breast cancer (BC): A translational analysis of four prospective multicentric studies

Background

Oncotype DX represents one of the genomic assays associated with the highest quality of evidence driving a strong recommendation for its use to guide decisions on adjuvant therapy for HR+/HER2- early BC patients. The clinical value of TILs in HR+/HER2- BC may be unearthed by focusing on patients whose tumors exhibit features of higher biological aggressiveness. Here we deepen and describe the correlation between RS and TILs, proposing an immuno-genomic model for HR+/HER2- BC.

Methods

We enrolled T1-T3, N0-N1 BC patients with available RS and TILs in the context of four multicenter, prospective studies primarily aimed at assessing the impact of the Oncotype DX® test on adjuvant treatment decisions in a clinical practice scenario. RS was categorized into: 0-10 (low risk), 11-25 (intermediate risk) and 26-100 (high risk); TILs were categorized into: low (0-10%), intermediate (11-59%) and high (60-100%).

Results

811 patients were included. RS distribution was (n=810): low risk 22.0%, intermediate risk 61.2%, high risk 16.8%. TIL distribution was (n=455): low TILs 84.6%, intermediate TILs 13.6% and high TILs 1.8%. A significant, weak positive, linear correlation was found between continuous TILs and RS (Pearson coefficient=0.223, p<0.001). When considering RS and TILs categories, tumors with intermediate/high TIL levels significantly enriched the high RS subgroup (p=0.006). This was confirmed both within Luminal A (Ki67<20% and PgR ≥20%) and Luminal B cohorts (ki67≥20% and/or PgR <20%). Among high-RS patients, 16.7% of Luminal A and 26.7% of Luminal B tumors had intermediate/high TILs.

Conclusions

We observed that RS and TILs capture only slightly overlapping information on the biology of HR+/HER2- tumor microenvironment. We demonstrated the feasibility of combining RS and TILs into a composite immuno-genomic model, which may identify patients simultaneously showing features of high biological/clinical risk and enhanced immunogenicity and may serve the purpose of guiding and focalizing patient selection in the further development of immunotherapy strategies for Luminal-like disease.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Fondazione AIRC under 5 per mille 2019 - ID. 22759 program to VG and IG20583 to EB; Institutional funds from UniPD (FM, MVD, VG).

Disclosure

F. Miglietta: Financial Interests, Personal, Speaker, Consultant, Advisor, outside the submitted work: Roche, Novartis, Gilead, Pfizer, Seagen. M.V. Dieci: Financial Interests, Personal, Invited Speaker: Eli Lilly, Exact sciences, Gilead, Seagen, Daiichi Sankyo, Novartis; Financial Interests, Personal, Advisory Board: Novartis, Eli Lilly, Seagen, Exact Science, Daiichi Sankyo, Gilead; Financial Interests, Personal, Other, Consultancy: Pfizer; Financial Interests, Personal, Other, Consultancy on educational project: Roche. T. Giarratano: Financial Interests, Personal, Speaker, Consultant, Advisor, outside the submitted work: Roche. E. Bria: Financial Interests, Personal, Advisory Board: AZ, Roche, BMS, MSD, Eli-Lilly, Amgen, Pfizer, Novartis; Financial Interests, Personal, Invited Speaker: AZ, Roche, BMS, MSD, Eli-Lilly, Pfizer, Novartis; Financial Interests, Institutional, Research Grant: AZ, Roche. A. Zambelli: Financial Interests, Personal, Advisory Board, outside the submitted work: Pfizer, Roche, Novartis, Lilly, Daiichi Sankyo, Seagen, AstraZeneca, MSD, ExactSciences. V. Guarneri: Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis, Amgen, GSK; Financial Interests, Personal, Advisory Board: Eli Lilly, Novartis, MSD, Gilead, Eli Lilly, Sanofi, Merck Serono, Exact Sciences, Eisai, Olema Oncology; Financial Interests, Institutional, Local PI: Eli Lilly, Roche, BMS, Novartis, AstraZeneca, MSD, Synton Biopharmaceuticals, Merck, GSK, Daiichi Sankyo, Nerviano; Non-Financial Interests, Member: ASCO. All other authors have declared no conflicts of interest.