<b><i>Introduction:</i></b> Inflammatory breast cancer (IBC) is an aggressive form of breast cancer with a poorly characterized immune microenvironment. <b><i>Methods:</i></b> We used a five-colour multiplex immunofluorescence panel, including CD68, CD4, CD8, CD20, and FOXP3 for immune microenvironment profiling in 93 treatment-naïve IBC samples. <b><i>Results:</i></b> Lower grade tumours were characterized by decreased CD4+ cells but increased accumulation of FOXP3+ cells. Increased CD20+ cells correlated with better response to neoadjuvant chemotherapy and increased CD4+ cells infiltration correlated with better overall survival. Pairwise analysis revealed that both ER+ and triple-negative breast cancer were characterized by co-infiltration of CD20 + cells with CD68+ and CD4+ cells, whereas co-infiltration of CD8+ and CD68+ cells was only observed in HER2+ IBC. Co-infiltration of CD20+, CD8+, CD4+, and FOXP3+ cells, and co-existence of CD68+ with FOXP3+ cells correlated with better therapeutic responses, while resistant tumours were characterized by co-accumulation of CD4+, CD8+, FOXP3+, and CD68+ cells and co-expression of CD68+ and CD20+ cells. In a Cox regression model, response to therapy was the most significant factor associated with improved patient survival. <b><i>Conclusion:</i></b> Those results reveal a complex unique pattern of distribution of immune cell subtypes in IBC and provide an important basis for detailed characterization of molecular pathways that govern the formation of IBC immune landscape and potential for immunotherapy.

F, The presentation, management and outcome of inflammatory breast cancer cases in the UK: Data from a multi-centre retrospective review,

Introduction: Historically, multiple synchronous breast cancers are defined as multifocal (MF) when they aoccur in the same quadrant of the breast, and multicentric (MC) they are in different quadrants; a number of authors continue to use this distinction. Multifocality has been reported to be an independent prognostic factor for survival and local recurrence. The molecular implications of MF and MC versus univocal breast cancers remain to be defined. We sought to investigate the incidence and molecular basis for this phenomenon. Materials and methods: Following a systematic review of the literature, breast cancer excisions reported by three specialist centers between 2005 and 2014 were investigated (n=4409 cases). Within this cohort, cases identified radiologically and confirmed histologically as mutifocal/multicentric were identified. Data on age at presentation, histological features and molecular profile were collected and compared between MF/MC breast cancer and the unifocal disease. Chi square test was used to compare categorical groups for ER, PR, HER2 and student t-test for mean age comparison. A p-values of ≤ 0.05 was considered significant. Results: 446 cases (10.12%) were reported as MF/MC invasive breast cancer. Most cases were treated by mastectomy. The majority of these were early breast cancer (Stage 1, 59.1% pT1(m), 72.2% pN0-1). Compared with unifocal breast cancer, patients with multifocal breast cancer were significantly younger (56.6 vs 59 years old, p=0.004) and more likely to have lymph node metastasis on presentation (50% vs 32%, p=0.001). There were differences, some significant, in the molecular profiles of unifocal cancers vs the largest focus of multifocals (ER positive: 80% vs 84% p=0.239, PR positive: 72% vs 76% p=0.301, HER2+ negative: 89% vs 76% p=0.002). Discussion: A significant proportion (one tenth) of breast cancer presented as multifocal disease. Differences in the immunohistochemical profile, in particular HER2 status, between MF and unifocal breast carcinomas are identified. Both the literature review and analysis of our available cases demonstrated a paucity of data on the incidence, degree of intratumor heterogeneity of multifocal breast cancers and its appropriate management. There are important questions unanswered about the molecular classification of multifocal breast cancer. Future genomic testing of those cases may highlight more pronounced differences. The findings form basis of a biomarker driven trial in set up comparing conservative surgery and mastectomy (MIAMI). Citation Format: Shaaban AM, Kaptanis S, Danial I, Smith S, Bradley S, Fernandez S, Mitsopoulos G, Ryan D, Winters Z, Jones L. Incidence and molecular phenotype of multifocal invasive breast carcinomas; A UK multi institutional series. [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 P6-05-06.