1499 Molecular and immune profiling of lobular-enriched versus non-lobular invasive breast cancers

• Published in: Journal for immunotherapy of cancer 2023-11, Vol.11 (Suppl 1), p.A1663-A1663
• Main Authors: Strickland, Kyle C, Pabla, Sarabjot, Ko, Heidi, Previs, Rebecca A, Wallen, Zachary D, Nesline, Mary K, Zhang, Shengle, Conroy, Jeffrey M, Jackson, Jennifer B, Saini, Kamal S, Jensen, Taylor J, Caveney, Brian, Eisenberg, Marcia, Reddy, Prasanth, Severson, Eric A, Ramkissoon, Shakti
• Format: Article
• Language: English
• Subjects: Antigens; Breast cancer; Gene expression; Immunotherapy; Tumors
• ISSN: 2051-1426
• DOI: 10.1136/jitc-2023-SITC2023.1499

BackgroundInvasive lobular carcinoma (ILC) is a morphologically distinct endocrine-sensitive sub-type of invasive breast cancer. Invasive ductal carcinoma has been extensively characterized, however, the genomic and immune characteristics of ILC are relatively understudied. It is known that the vast majority of ILCs harbor alterations in CDH1, the gene encoding E-cadherin, but a more thorough understanding of the genomic and immune profiles of lobular-type carcinomas may provide insight into the underlying molecular mechanisms of tumorigenesis, metastasis, and potential therapeutic strategies to counter resistance mechanisms.MethodsWe performed comprehensive genomic and immune profiling on 528 invasive breast cancers using panel-based next-generation DNA (523 genes) and RNA sequencing (55 genes for fusions/splice site variants, 395 for immune gene expression). PD-L1 expression was assessed by combined positive score (CPS) following 22C3 immunohistochemistry. Diagnostic and molecular pathology reports were reviewed by a board-certified anatomic pathologist for all tumors that harbored mutations in CDH1 or had a diagnosis of ILC from the test order to create a ’lobular-enriched’ (LE) cohort, which was compared to other non-lobular (NL) breast carcinomas, which included CDH1-mutated tumors diagnosed as ductal-type carcinomas. For each tumor, we determined immune-related expression signatures, including a tumor immunogenicity score (TIGS, 161 genes), a cellular proliferation signature (CP, 10 genes including Ki-67), and a cancer testis antigen burden score (CTAB, 21 genes). Differences between cohorts were assessed using the Mann-Whitney test.ResultsThe LE cohort contained 52 tumors (including 30 ILCs, 20 mammary carcinomas not otherwise specified, and 2 mammary carcinomas with lobular features), and the non-lobular (NL) cohort contained 476 cases (including 14 cases of CHD1-mutated ductal carcinomas). Compared to NL tumors, LE tumors were sequenced at advanced age (68.95 vs. 62.30 y, p