Abstract 981: Lymphocytic inflammation is a distinct feature of squamous metaplastic breast carcinomas and is associated with metastasis

Metaplastic breast carcinoma (MBC) is a rare subtype of triple negative breast carcinoma with frequent metastasis and poor response to chemotherapy. MBCs are defined by the presence of “metaplastic” components of spindle, squamous, or sarcomatoid histology (e.g. chondroid, osseous). To elucidate the molecular determinants of MBC, our lab analyzed the proteomics landscape of MBC which revealed that squamous MBC are significantly enriched for proteins that mediate inflammation and leukocyte activation, compared to spindle and sarcomatoid MBC. The presence and the significance of inflammation in MBC has not been investigated. To evaluate this, we retrieved 36 MBCs resected from 1988-2015 at our institution. Tumor sections were reviewed by three pathologists, and used to develop a tissue microarray (TMA) in duplicate. H&E whole sections were reviewed for MBC subtype and inflammation. The inflammatory infiltrate was assessed for type (lymphocytes, plasma cells, neutrophils, macrophages), localization (peripheral and/or intratumoral), and degree (0, 1, 2, 3). When the combined degree of inflammation at the periphery and intratumoral was ≥ 4, the degree was considered high. TMAs were immunostained for CD3/CD20 and CD4/CD8 double stains for further characterization. Of the 36 MBCs, 9 (25%) were chondroid, 7 (20%) were spindled, and 20 (55%) were squamous. When present, inflammation was predominantly lymphoid or lymphoplasmacytic (94%). Seventy-five % (15/20) of squamous MBC demonstrated significantly higher intratumoral inflammation (score ≥2) compared to 43% (3/7) and 11% (1/9) of spindle and chondroid, respectively (p=0.005). Squamous MBCs had a significantly higher degree (peripheral and intratumoral) of inflammation (15/20, 75%) compared to spindled (3/7, 43%) and chondroid (1/9, 11%) MBC's (p=0.004). The inflammatory infiltrate consisted of a mixture of B and T lymphocytes. Ninety-five % of cases with a T-cell infiltrate showed a predominance of CD4+ over CD8+ T-cells. Lymph node metastasis was seen in 11/30 MBC, and 9/11 (81%) demonstrated squamous morphology and a high degree of inflammation (p=0.017). Our results demonstrate that squamous MBC have a higher degree of inflammation within and at the periphery of the tumor compared to other MBC subtypes. A high degree of inflammation consisting of B and T lymphocytes in squamous MBC correlates with lymph node metastasis. The inflammatory infiltrate may contribute to the aggressive clinical behavior of squamous MBC, which warrants further investigation. Citation Format: Emily McMullen, Stephanie L. Skala, Sabra Djomehri, May P. Chan, Celina G. Kleer. Lymphocytic inflammation is a distinct feature of squamous metaplastic breast carcinomas and is associated with metastasis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 981.