HR+/HER2- BC is less immunogenic compared to triple-negative BC in the early setting. Lower levels of stromal tumor infiltrating lymphocytes (sTIL) are observed in BC metastases compared to the primary tumor. sTIL have not yet been investigated extensively in metastatic HR+/HER2- BC. Here, we aimed at evaluating sTIL in multiple metastatic lesions from patients with primary HR+/HER2- BC who participated in our institutional post-mortem tissue donation program UPTIDER (NCT04531696).
16 patients with HR+ (ER+ and/or PR+)/HER2- primary BC, enrolled between 01/01/2021 and 08/01/2023 were considered. sTIL were assessed according to international guidelines (PMID:28777142) and scored at the invasive margin on a total of 542 samples (481 metastatic (M) and 46 primary untreated (P)). A median of 25.5 M lesions were evaluated per patient (IQR: 20.5-38.75). M lymph nodes were only scored if there was extra nodal extension into the surrounding tissue. Central pathology evaluation was performed for histology and ER-status (EP1 clone, RTU, CE IVD). Associations between sample status (outcome: M vs P/ER+ vs ER- for M) and sTIL levels (co-variate) were assessed by logistic linear regression with data clustering by patient using the generalized estimating equation method.
A median of 4 (range:1-13, IQR:2-7) and 2 metastases (range:1-4, IQR:1-2.5) per patient had a sTIL score >5% and 10%, respectively. M sTIL scores were heterogeneous within patients (range of 16 sTIL ranges:2.34-40, median of 16 sTIL IQR’s:1.68, range of 16 sTIL IQR’s:0.34-6.34). P had higher sTIL scores compared to M (OR:0.94, 95% CI:0.89-1.00, p:0.05). 50/316 (16%) metastases lost ER expression in 12 patients with ER+ primary BC. No significant difference was detected in sTIL scores between ER+ and ER- M (OR:1.06, 95% CI:0.98-1.14, p:0.15) while higher sTIL scores were observed in NST M (n=230) compared to ILC M (n=209) (Estimate:1.1, 95% CI: -0.07-2.3, p:0.06).
This study highlights the intra-patient inter-metastasis heterogeneity in sTIL scores, differences between P and M, as well as differences according to histology in HR+/HER2- BC patients.
Laboratory for Translational Breast Cancer Research.
KU Leuven, Leuven, Belgium.
K. Punie: Financial Interests, Institutional, Advisory Board: AstraZeneca, Novartis, Roche, Vifor Pharma, Eli Lilly, Pierre Fabre, McCann Health, Roularta, Teva, Gilead Sciences, Pfizer, Gilead, MSD; Financial Interests, Institutional, Invited Speaker: Pfizer, Roche, Novartis, Eli Lilly, Mundi Pharma, MSD, Medscape, MSD; Financial Interests, Institutional, Other, Consultancy: Roche; Financial Interests, Personal, Other, Consultancy: Gilead, Novartis, MSD, Roche; Financial Interests, Personal, Invited Speaker: Sanofi, AstraZeneca; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Institutional, Funding: Sanofi; Non-Financial Interests, Principal Investigator: EORTC 1745-ETF-BCG trial; Non-Financial Interests, Other, Committee member: ESMO Young Oncologists Committee; Non-Financial Interests, Invited Speaker: BSMO; Non-Financial Interests, Other, Committee Member: ESMO Resilience Task Force; Non-Financial Interests, Advisory Role: Commission personalized medecine Federal Government Belgium; Non-Financial Interests, Advisory Role, External Scientific Advisor: European Medicine Agency. H. Wildiers: Financial Interests, Institutional, Advisory Board: Roche, Lilly, AstraZeneca, Daiichi Sankyo, PSI Cro AG, KCE, MSD, MSD, E Squared Communications LLC; Financial Interests, Institutional, Invited Speaker: Eisai, AstraZeneca; Financial Interests, Institutional, Other, Consultancy fee: AbbVie, Immutep Pty; Financial Interests, Institutional, Expert Testimony: Daiichi Sankyo; Financial Interests, Institutional, Other, Consultancy: Daiichi Sankyo; Financial Interests, Institutional, Research Grant, Grant to the Leuven Breast Center to support the research database: Roche; Financial Interests, Institutional, Research Grant, Grant to institute to perform a multicentric national academic trial: Novartis; Other, Travel & accomodations: Pfizer; Other, Travel & accomodation: Roche; Other, Subscription fee: Gilead. G. Floris: Financial Interests, Institutional, Advisory Board: AstraZeneca. All other authors have declared no conflicts of interest.