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

Background

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) of HER2-neg BC according to ER status (ER-neg: 0% vs ER-low: 1-9%).

Methods

This multicentric study included patients with stage I-III HER2-neg BC from centers across Italy and France: Istituto Oncologico Veneto IOV; Montpellier Cancer Institute MCI; Istituto Nazionale Tumori Milano; Istituto Europeo di Oncologia. Tumor samples were reviewed for ER: ER-neg and ER-low pts were eligible, pts with ER intermediate expression (ER-int: 10-50%) were included in a control cohort. Tumor-infiltrating lymphocytes (TILs) were evaluated on full-face H&E slides. CD8, FOXP3 and PD-L1 (SP142) status was assessed by IHC and quantified by digital pathology in samples from IOV (full-face slides) and MCI (tissue-microarray).

Results

Of 753 pts included, 613 had ER-neg BC, 80 had ER-low BC, and 60 had ER-int disease. TME characterization in these tumor specimens is summarized in the table. TILs levels were similar in ER-neg and ER-low tumors, and in both subgroups significantly higher than in ER-int samples. Compared to ER-neg, ER-low BC had significantly higher levels of CD8+ and FOXP3+ cells, with a similar CD8/FOXP3 ratio. The rate of PD-L1 -positive tumors was similar between ER-neg and ER-low BC pts. At the validated ≥30% cut-off, higher TILs were associated with better relapse-free survival in ER-neg (5-yr rates: 89% vs 71%, p<0.001) and ER-low BC pts (93% vs 58%, p=0.047), but not in the ER-int group, where we found an opposite trend (43% vs 69%, p=0.114). Table: 1MO

Table: 1MO

Conclusions

TME composition is similar in ER-neg vs ER-low HER2-neg BC tumors and TILs have a similar prognostic role in these cohorts. Our results support the claim that HER2-neg/ER-low BC pts should be granted access to drugs developed for triple-negative BC, including immune checkpoint inhibitors. Gene expression analysis will be presented at the meeting.

Legal entity responsible for the study

The authors.

Funding

Funding from Merck KGaA, Darmstadt, Germany and Institutional funding from Istituto Oncologico Veneto - Ricerca Corrente.

Disclosure

D. Massa: Financial Interests, Personal, Sponsor/Funding, Travel Support: Eli Lilly. C. Vernieri: Financial Interests, Personal, Advisory Role: Novartis, Daiichi Sankyo, Pfizer; Financial Interests, Personal, Invited Speaker: Novartis, Eli Lilly, Istituto Gentili; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Other, Travel Grant: Novartis, Daiichi Sankyo, Pfizer, Eli Lilly, Istituto Gentili. C. Criscitiello: Financial Interests, Personal, Invited Speaker: Pfizer, Novartis, Eli Lilly, Roche, Gilead; Financial Interests, Personal, Advisory Board: MSD, Seagen, AstraZeneca, Daiichi Sankyo. G. Griguolo: Financial Interests, Personal, Advisory Board: Gilead; Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis; Financial Interests, Personal, Other, Travel Support: Gilead, Eli Lilly, Pfizer, Novartis, Daiichi Sankyo, Amgen. F. Miglietta: Financial Interests, Personal, Sponsor/Funding: Roche, Novartis, Gilead. A. Vingiani: Financial Interests, Personal, Invited Speaker: Roche, Eli Lilly. R. Lobefaro: Financial Interests, Personal, Advisory Role: Pfizer, Lilly, Daiichi Sankyo, AstraZeneca. G. Pruneri: Financial Interests, Personal, Advisory Board: ADS Biotec; Financial Interests, Personal, Other, Honoraria: Exact Sciences, Novartis, Eli Lilly, AstraZeneca; Financial Interests, Personal, Research Grant: Roche. M. Fassan: Financial Interests, Personal, Advisory Role: Astellas Pharma, Pierre Fabre, MSD, AstraZeneca, Janssen, GlaxoSmithKline, Amgen, Novartis , Roche; Financial Interests, Personal, Research Grant: Astellas Pharma, QED Therapeutics, Diaceutics and Macrophage Pharma. G. Curigliano: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Daiichi Sankyo, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Daiichi Sankyo, Lilly, Pfizer, Veracyte, BMS, Merck, Exact Sciences, Celcuity; Financial Interests, Personal, Other, Advisory Board: Ellipsis; Financial Interests, Institutional, Research Grant, Investigator Initiated Trial: Merck; Financial Interests, Institutional, Funding, Phase I studies: BMS, Novartis, AstraZeneca, Daiichi Sankyo, Roche, Blueprint Medicine, Kymab, Astellas, Sanofi, Philogen; Financial Interests, Institutional, Invited Speaker, Phase I clinical basket trial: Relay Therapeutics; Non-Financial Interests, Officer, Italian National Health Council as Advisor for Ministry of Health: Consiglio Superiore di Sanità; Non-Financial Interests, Advisory Role, Member of the Scientific Council. Patient advocacy association: Europa Donna; Non-Financial Interests, Advisory Role, Cancer Research Foundation: Fondazione Beretta; Non-Financial Interests, Invited Speaker, No compensation for this role. This a public national company for cancer prevention: Lega Italiana Lotta ai Tumori; Non-Financial Interests, Officer, Member of the Advisory Council: EUSOMA; Non-Financial Interests, Officer, ESMO Clinical Practice Guidelines Chair: ESMO. V. Guarneri: Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis, Amgen, GSK; Financial Interests, Personal, Advisory Board: Eli Lilly, Novartis, MSD, Gilead, Sanofi, Merck Serono, Exact Sciences, Eisai, Olema Oncology; Financial Interests, Personal, Expert Testimony: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Eli Lilly, Roche, BMS, Novartis, AstraZeneca, MSD, Synton Biopharmaceuticals, Merck, Glaxo Smith Kline, Daiichi Sankyo, Nerviano; Non-Financial Interests, Member: ASCO. W. Jacot: Financial Interests, Personal, Advisory Board: AstraZeneca, Eisai, Novartis, Roche, Pfizer, Eli Lilly, MSD, BMS, Chugai, Seagen, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Seagen, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: AstraZeneca, Daiichi Sankyo; Financial Interests, Invited Speaker: Roche, Novartis, Daiichi Sankyo, Daiichi Sankyo. M.V. Dieci: Financial Interests, Personal, Advisory Role: Eli Lilly, Pfizer, Novartis, Seagen, Gilead, MSD, Exact Sciences, AstraZeneca, Roche, Daiichi Sankyo. All other authors have declared no conflicts of interest.