Abstract P3-07-47: Comprehensive profiling of metaplastic breast carcinoma reveals frequent over-expression of PD-L1

Abstract

Abstract Background: Metaplastic breast carcinoma (MBC) is a rare subtype of breast carcinoma less responsive to conventional chemotherapy relative to usual breast carcinomas (UBCs) such as ductal and lobular subtype. In molecular terms MBC usually clusters with triple negative breast cancer (TNBC), but MBCs portray a worse prognosis in comparison to TNBCs. Published studies investigating MBCs for specific biomarkers of therapy response are rare and limited by the methodological approaches. Methods: This study included 132 patients with 38 histologically confirmed MBCs and 94 UBCs. Amongst the 94 UBCSs, 44 were estrogen receptor positive, 33 were triple negative and 17 were HER2 positive. Direct sequencing analysis was performed on genomic DNA isolated from formalin-fixed paraffin-embedded tissue (FFPE) using the Illumina MiSeq Next Generation Sequencing platform (NGS). Immunohistochemistry for PD-L1 (SP142, Spring Bioscience), PD-1 (NAT105, Ventana) and EGFR (31G7, Life Technologies) was performed using automated procedures. Additionally, mutation analysis for EGFRvIII was performed on RNA extracted from FFPE tissue. Results: At the genomic level, numerous cases of MBC had multiple genomic alterations with the most frequent genetic mutation in TP53 gene (14/24), similar to the TNBC controls (17/33). BRCA1 mutations were detected in 2/10 cases. Potentially actionable mutations were rare and included PIK3CA gene. Importantly, PD-L1 expression on cancer cells was detected in significantly higher proportion of MBCs (37%) than in the UBC cohort (6%) or TNBC control (14%) (p=3.7x10-5 and p=0.03, respectively). PD-1 positive tumors infiltrating lymphocytes (TILS) varied greatly in MBC (0 to >50/mm2). Over-expression of EGFR was frequent in MBCs (62%); however no mutations in the gene including EGFRvIII were detected. Conclusion: Comprehensive profiling of a large cohort of this rare carcinoma highlighted predominance of TP53 mutations, wild type EGFR gene expression, a distinct increase in proportion of PD-L1 expression in carcinoma cells, and PD-1 expression in TILS. The latter properties can be exploited in clinical trials utilizing immune check point inhibitors. Citation Format: Gatalica Z, Joneja U, Ghazalpour A, Swensen J, Feldman R, Cai F, Chen W, Xiao N, Reddy S, Palazzo J. Comprehensive profiling of metaplastic breast carcinoma reveals frequent over-expression of PD-L1. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-47.