Treatment response, tumor infiltrating lymphocytes and clinical outcomes in inflammatory breast cancer treated with neoadjuvant systemic therapy.

Inflammatory breast cancer (IBC) is a rare (1-5%), aggressive form of BC, accounting for ~10% of BC mortality. In the localized setting, standard of care is neoadjuvant chemotherapy (NACT) +/- anti-Human Epidermal growth factor receptor 2 (HER2) therapy, followed by surgery. Here we investigated associations between clinicopathological variables, stromal tumor-infiltrating lymphocytes (sTIL), and pathological complete response (pCR), and the prognostic value of pCR. We included 494 localized IBC patients treated with NACT from 10/1996 to 10/2021 in eight European hospitals. Standard clinicopathological variables were collected and central pathological review was performed, including sTIL. Associations were assessed using Firth's logistic regression models. Cox regressions were used to evaluate the role of pCR and residual cancer burden (RCB) on disease-free survival (DFS), distant recurrence-free survival (DRFS) and overall survival (OS). Distribution according to receptor status was as follows: 26.4% estrogen receptor-negative (ER-)/HER2-; 22.0% ER-/HER2+; 37.4% ER+/HER2- and 14.1% ER+/HER2+. Overall pCR rate was 26.3%, being highest in the HER2+ groups (45.9% for ER-/HER2+ and 42.9% for ER+/HER2+). sTIL were low (median: 5.3%), being highest in the ER-/HER2- group (median: 10%). High tumor grade, ER-negativity, HER2-positivity, higher sTIL, and taxane-based NACT were significantly associated with pCR. pCR was associated with improved DFS, DRFS, and OS in multivariable analyses. RCB-score in patients not achieving pCR was independently associated with survival. In conclusion, sTIL were low in IBC, but were predictive of pCR. Both pCR and RCB have an independent prognostic role in IBC treated with NACT.