Introduction: Inflammatory breast cancer (IBC) is a rare, but aggressive form of breast cancer. Increasing evidence indicates that immune cells in the tumor micro-environment play an important role in IBC progression: infiltration with stromal Tumor Infiltrating Lymphocytes (sTIL) is associated with a better response to neo-adjuvant chemotherapy (NACT) and longer overall survival in IBC patients. However, the prognostic role of sTIL in patients without a complete pathological response (pCR) after NACT remains unclear. In this study we evaluated the effect of NACT on sTIL in IBC and locally advanced non-inflammatory breast cancer (LABC) and the prognostic impact of sTIL in IBC.

Methodology: In this retrospective case-control study we evaluated sTIL in patients with IBC (n=60) and LABC (n= 134) that received anthracyclin-taxane based NACT. Tumor tissue was sampled as part of the routine work-up, before (diagnostic biopsy) and after (resection specimen) NACT. sTIL scoring was performed on Haematoxylin & Eosin stained 5-µm sections of formalin-fixed paraffin-embedded tumor tissue by two different researchers according to the recommendations by the International TILs Working Group. In case of discrepancy, the sample was scored by a third observer in order to obtain a consensus score. sTIL difference between pre-treatment and post-treatment specimen was called δsTIL. Cellularity of the residual cancer after NACT was evaluated according to the MD Anderson Residual Cancer Burden (RCB) method.

Results: Most of the IBC patients presented with a hormone receptor (HR) positive carcinoma (n=35/60, 58.3%) and 25 patients had pCR after NACT (42%); the latter patients had less than 1% sTIL in the tumor bed area. Besides having histologically more poorly differentiated tumors (P= 0.033), no significant clinicopathological differences between the IBC and LABC cohort were observed. There was no significant difference in the pre-treatment median sTIL score between IBC (12.5%, range: 1% - 80%) and LABC (10%, range: 1% - 85%). Furthermore, both in the IBC (median δsTIL: -4.5%, P= 0.01) and in the LABC (median δsTIL: -1%, P= 0.06) cohort the number of sTIL was lower after NACT. This decrease was significantly greater in the IBC cohort (P= 0.04). In a multivariate model - including HR and HER2 status, histological differentiation grade, nodal status and IBC/LABC phenotype - IBC disease correlated with a stronger decrease of sTILs after NACT (OR: 0.31, 95% CI 0.10 - 0.89, P= 0.04).

As we previously demonstrated, higher sTIL score before NACT was associated with better overall survival (OS) (P= 0.006) in IBC. IBC patients without pCR, but with a stronger decrease (> 4.5 %) of the number of sTIL after NACT had a better OS (P= 0.04) and disease-free survival (DFS) (P= 0.04). There was a significant correlation between δsTIL and both higher sTIL score before NACT (P< .001) and lower residual cancer cellularity (P= 0.02). However, in a multivariate model - including sTIL before NACT, δsTIL and residual cancer cellularity - both a strong decrease of sTIL (HR: 0.32; 95% CI 0.10 - 1.00; P= 0.05) and a low residual cancer cellularity (HR: 0.22; 95% CI 0.07 - 0.68; P= 0.009) were independent predictors of a better DFS.

Conclusion: Both the IBC and LABC cohort had the same number of sTIL before NACT. However, the IBC phenotype was associated with a stronger decrease of sTIL after NACT independent of molecular subtype and nodal stage. Furthermore, a strong decrease in sTIL was an independent predictor of better prognosis in IBC.

Citation Format: Christophe Van Berckelaer, Leonie Vercauteren, Iris Vermeiren, Glenn Broeckx, Steven Van Laere, Luc Dirix, Cecile Colpaert, Peter Van Dam. The prognostic role of tumor-infiltrating lymphocytes after treatment with neo-adjuvant chemotherapy in inflammatory breast cancer patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS17-13.