Abstract P6-01-47: Stromal tumor infiltrating lymphocytes and pathological complete response in patients with inflammatory breast cancer treated with neoadjuvant chemotherapy
Authors: De Schepper Maxim , Nguyen Ha-Linh , Richard François , Lerebours Florence , Vion Roman , Clatot Florian , Berghian Anca , Maetens Marion , Leduc Sophia , Isnaldi Edoardo , Molinelli Chiara , Lambertini Matteo , Grillo Frederica , Zoppoli Gabriele , Dirix Luc , Wuyts Hilde , Punie Kevin , Wildiers Hans , Remmerie Chantal , Smeets Ann , Nevelsteen Ines , Neven Patrick , Salomon Anne , Larsimont Denis , Duhem Caroline , Viens Patrice , BERTUCCI François , Biganzoli Elia , Vermeulen Peter , Floris Giuseppe , Desmedt Christine 
Published: March 2023

Abstract
Background: Inflammatory breast cancer (IBC) is a rare (1-5%), but aggressive form of breast cancer (BC), accounting for ~10% of BC mortality. In early setting (M0), standard of care is neoadjuvant chemotherapy (NACT), followed by surgery. Nevertheless, outcome is still relatively poor. Pathological complete response (pCR) after NACT is prognostic in BC in general, and can be predicted by a high percentage of stromal tumor infiltrating lymphocytes (sTIL) in the primary tumor. The predictive value of sTIL in IBC has only been sporadically investigated, often in smaller series. Our aim was to determine which variables, including sTIL, are associated with pCR and to determine the prognostic value of pCR in IBC in a large multicentric, retrospective cohort. Patients & Methods: We included patients with IBC treated with NACT+/- anti-Human Epidermal growth factor Receptor 2 (HER2) therapy, followed by surgery from 10/1996 to 10/2021 in 7 different European hospitals. Clinicopathological variables were collected and central pathological review was performed, including sTIL scoring. This study focused on M0 cases. Considered clinicopathological variables were: age, histology, tumor grade, estrogen receptor status (ER), HER2 status, focality (unifocal vs not), and baseline locoregional nodal status (Table 1). Associations between pCR, clinicopathological variables and sTIL were assessed using Firth’s logistic regression models: Model 1 was adjusted for center, Model 2 additionally included all variables of interest. Similarly, linear regression was used to investigate the association between sTIL and clinicopathological features. Univariable and multivariable Cox regression was used to evaluate the role of pCR on disease free survival (DFS), distant recurrence free survival (DRFS) and overall survival (OS). DFS and DRFS were analyzed considering death without the respective event as competing risk. Results: 494 patients were included. The distribution according to receptor status was: ER-/HER2- (24.3%), ER+/HER2- (34.4%), ER+/HER2+ (13%) and ER-/HER2+ (20.2%). pCR rate was 26% and per receptor status: ER-/HER2- (28%), ER+/HER2- (10%), ER+/HER2+ (42%) and ER-/HER2+ (45%). pCR was associated with grade (G3 vs G1/2, OR =2.79 (1.70 − 4.74), p &lt; .001), ER-status (positive vs negative, OR = 0.39 (0.26 − 0.60), p &lt; .001) and HER2 status (positive vs negative, OR = 3.74 (2.43 − 5.81), p &lt; .001) in Model 1. Only the association with HER2 status remained significant in Model 2 (OR = 5.34 (2.83 − 10.47), p &lt; .001). sTIL was scored for 385 patients. Median sTIL was 5.3% [IQR 2.0%;16.7%] and according to receptor status: ER-/HER2- (10%), ER+/HER2- (2.5%), ER+/HER2+ (6.7%) and ER-/HER2+ (8.3%). Higher sTIL was associated with NST (p = .032), grade 3 (p = .015), and ER-negativity (p = .007) in Model 1. This was no longer significant in Model 2, but the direction of the trends was preserved. sTIL was associated with pCR (5% increment, OR = 1.13 (1.05 − 1.22), p = .002), but no longer after adjustment. No association between pCR and sTIL was found stratifying by receptor status. The median FU was 9.4 years and multivariable Cox regression models revealed that ER+ and HER2+ status and achieving pCR were significantly associated with better DFS, DRFS, and OS (Table 1). Conclusion: Our results indicate that patients with HER2+ tumors have a higher probability of achieving pCR and that pCR has an independent prognostic role in IBC. This is the largest IBC study with centrally scored sTIL, demonstrating that sTIL is associated with pCR but its role as an independent predictor of pCR is still not certain.
Citation Format: Maxim De Schepper, Ha-Linh Nguyen, François Richard, Florence Lerebours, Roman Vion, Florian Clatot, Anca Berghian, Marion Maetens, Sophia Leduc, Edoardo Isnaldi, Chiara Molinelli, Matteo Lambertini, Frederica Grillo, Gabriele Zoppoli, Luc Dirix, Hilde Wuyts, Kevin Punie, Hans Wildiers, Chantal Remmerie, Ann Smeets, Ines Nevelsteen, Patrick Neven, Anne Salomon, Denis Larsimont, Caroline Duhem, Patrice Viens, François BERTUCCI, Elia Biganzoli, Peter Vermeulen, Giuseppe Floris, Christine Desmedt. Stromal tumor infiltrating lymphocytes and pathological complete response in patients with inflammatory breast cancer treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-47.