1MO Tumor immune microenvironment in ER-negative vs ER-low, HER2-neg breast cancer

The recommended cut-off of <1% positive cells to define estrogen receptor (ER) negative status in breast cancer (BC) is highly debated. We compared the tumor immune microenvironment (TME) HER2-neg BC according ER (ER-neg: 0% vs ER-low: 1-9%). This multicentric study included patients with stage I-III from centers across Italy and France: Istituto Oncologico Veneto IOV; Montpellier Cancer Institute MCI; Nazionale Tumori Milano; Europeo di Oncologia. Tumor samples were reviewed for ER: ER-neg ER-low pts eligible, intermediate expression (ER-int: 10-50%) a control cohort. Tumor-infiltrating lymphocytes (TILs) evaluated on full-face H&E slides. CD8, FOXP3 PD-L1 (SP142) was assessed by IHC quantified digital pathology IOV (full-face slides) MCI (tissue-microarray). Of 753 included, 613 had BC, 80 60 ER-int disease. TME characterization these specimens summarized table. TILs levels similar tumors, both subgroups significantly higher than samples. Compared ER-neg, CD8+ FOXP3+ cells, CD8/FOXP3 ratio. rate -positive tumors between pts. At validated ≥30% cut-off, associated better relapse-free survival (5-yr rates: 89% 71%, p<0.001) (93% 58%, p=0.047), but not group, where we found an opposite trend (43% 69%, p=0.114).Tabled 1Table: 1MOTILsER-neg (n=613)ER-low (n=80)ER-int (n=60)PTILs median (Q1:Q3)6% (3:20)10% (5:20)5% (2:10)ER-neg ER- low: 0.093ER-neg ER-int: 0.026ER-low 0.003CD8 FOXP3ER-negER-lowP(n=219 IOV, n=248 MCI)(n=30 n=19 MCI)CD8 cells/mm2IOV (Q1:Q3)227 (103:562)343 (201:545)0.040MCI (Q1:Q3)341 (86:760)1100 (168-1596)0.071FOXP3 (Q1:Q3)53 (19:122)91 (44:168)0.011MCI (Q1:Q3)2 (0:22)38 (1:91)0.036CD8/FOXP3 ratioIOV (Q1:Q3)4 (2:8)4 (2:7)0.495MCI (Q1:Q3)29 (6:98)15 (5:33)0.464PD-L1ER-negER-lowP(n=77 n=249 MCI)(n=13 n=17 MCI)PDL1 ≥1%IOV (%)64.9%69.2%0.091MCI (%)73.9%94.1%0.062 Open table new tab composition have prognostic role cohorts. Our results support claim that HER2-neg/ER-low should be granted access drugs developed triple-negative including checkpoint inhibitors. Gene analysis will presented at meeting.