Immune and molecular determinants of response to neoadjuvant chemotherapy in inflammatory breast cancer.

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11501 Background: Inflammatory breast cancer (IBC) is the most aggressive form of primary breast cancer and has poor responses to standard of care neoadjuvant chemotherapy (NAC). Given there is a limited understanding of the immune microenvironment of IBC, this study aims to characterize the immune and molecular profiles of stage III and IV IBC and to identify biomarkers of response to treatment and targets for future therapies. Methods: IBC patients with available pre-treatment tumor samples and with intent to take to mastectomy were identified in the IBC tumor registry and tissue bank. Tumor infiltrating lymphocyte (TIL) infiltration in the tumor stroma was quantified on H&E slides per consensus guidelines (n = 91). On a subset of patients with available samples, deeper immune profiling was performed, including quantification of CD8 T cells by immunohistochemistry (IHC) (n = 33), PD-L1 tumor expression by IHC (n = 14), myeloid cells by multiplex IHC (n = 15), T cell clonality by T cell receptor sequencing (n = 22), and total mutational load (TML) by whole exome sequencing (n = 20). Results: Mean TIL were higher in tumors from patients that achieved a pathological complete response (pCR) to NAC than from those that did not (13.79 vs 7.24%, p = 0.019) and in patients with stage III compared to stage IV disease (11.90 vs 4.79%, p < 0.001). Though no statistically significant differences in CD8 infiltrate by response, stage, or receptor status were seen, the presence of a more clonal T cell population was predictive of pCR (13.27 vs 5.70% top 5 clone frequency, p = 0.042 among stage III patients). Myeloid cell staining revealed that tryptase staining, indicative of mast cells, was inversely associated with pCR (28.26 vs 108.0 counts/mm2, p = 0.011). Three of fourteen patient tumors displayed low PD-L1 tumor positivity (range 1-2%, 1+-2+) with the others being negative. Genomic profiling showed no statistically significant differences in TML by stage, receptor status, response, or immune infiltrate. Conclusions: Higher TIL, more clonal T cells, and lower mast cell infiltration are predictive of response to NAC in IBC. Comprehensive immune characterization of a larger cohort of pre- and post-treatment samples is currently underway.