Prognostic Impact of Stromal Immune Infiltration before and after Neoadjuvant Chemotherapy (NAC) in Triple Negative Inflammatory Breast Cancers (TNIBC) Treated with Dose-Dense Dose-Intense NAC

SIMPLE SUMMARY: Inflammatory breast cancers (IBC) are very aggressive especially the triple negative ones, highlighting the importance of prognostic and predictive factors determination. The evaluation of tumor infiltrating lymphocytes (TIL) is advised in breast cancers but little is known in inflammatory breast cancers, especially the TIL variation, before and after neoadjuvant chemotherapy (NAC). We reported a series of 31 triple negative IBC treated with dose-dense dose-intense NAC and investigated post NAC TIL and TILs variation. We showed that pre-NAC immune infiltration was lower than in the non-inflammatory breast cancer and that TIL increase after NAC is associated with a decrease in EFS. These results suggest that patients whose tumors have TIL enrichment after NAC are at high risk of relapse and could be candidates for adjuvant treatment after NAC. ABSTRACT: Inflammatory breast cancers are very aggressive, and among them, triple negative breast cancer (TNBC) has the worst prognosis. While many studies have investigated the association between tumor-infiltrating lymphocytes (TIL) before neoadjuvant chemotherapy (NAC) and outcome in TNBC, the impact of post-NAC TIL and TIL variation in triple negative inflammatory breast cancer (TNIBC) outcome is unknown. Between January 2010 to December 2018, all patients with TNIBC seen at the breast disease unit (Saint-Louis Hospital) were treated with dose-dense dose-intense NAC. The main objective of the study was to determine factors associated with event-free survival (EFS), particularly pathological complete response (pCR), pre- and post-NAC TIL, delta TIL and post-NAC lymphovascular invasion (LVI). After univariate analysis, post-NAC LVI (HR 2.06; CI 1.13–3.74; p = 0.02), high post-NAC TIL (HR 1.81; CI 1.07–3.06; p = 0.03) and positive delta TIL (HR 2.20; CI 1.36–3.52; p = 0.001) were significantly associated with impaired EFS. After multivariate analysis, only a positive TIL variation remained negatively associated with EFS (HR 1.88; CI 1.05–3.35; p = 0.01). TNIBC patients treated with intensive NAC who present TIL enrichment after NAC have a high risk of relapse, which could be used as a prognostic marker in TNIBC and could help to choose adjuvant post-NAC treatment.