Abstract P3-05-10: Impact of neoadjuvant systemic therapy on sTIL in breast cancer
Authors: Armaghani A , Asirvatham R , Mramba L , Daily K 
Published: February 2018

Abstract
Background
Multiple studies have shown a correlation between the presence of stromal tumor infiltrating lymphocytes (sTIL) and breast cancer outcomes. Higher sTIL are associated with higher rates of pCR, DFS, and OS. These findings have been primarily observed in TNBC and in HER2+ rather than in HR+, which overall has lower sTIL. Despite this growing body of prognostic evidence, there is little data comparing sTIL at diagnosis to sTIL after neoadjuvant systemic treatment. Understanding the impact of treatment on sTIL may lead to novel techniques to increase host immune response in the tumor microenvironment. The objective of this study was to correlate sTIL in paired samples before and after standard neoadjuvant systemic therapy, and then to identify the direction and magnitude of change in sTIL along with any associated features.
Methods
Institutional pathology database was queried for invasive breast carcinoma with “yp” in staging designation. From July 2013 to September 2016, there were 122 cases identified. When cases were excluded due to unavailable biopsy slides, there were 61 cases remaining. Needle biopsy and finalsurgical specimens were evaluated using International TIL Working Group 2014 guidelines and reported as a whole number percentage. In specimens with pCR, where there are no applicable guidelines, sTIL were determined by estimating the lymphoplasmacytic infiltrate in the tumor bed. Additional information gathered from the electronic medical record included patient age, clinical TNM stage, breast cancer subtype (HR+, HER2+, TNBC), neoadjuvant systemic therapy regimen (anthracycline, nonanthracycline, Trastuzumab-containing, endocrine), and response to treatment (pCR, residual invasive disease). A negative binomial generalized linear mixed model was used for analysis.
Results
Overall the sTIL declined from biopsy to surgery by about 36% (β = -0.448, S.E. = 0.223, pvalue = 0.045). However, there were 19/61 patients who had an increase in sTIL with neoadjuvant systemic therapy. For this group, the mean biopsy sTIL was 9.7% while the mean surgery sTIL was 28.7%, significantly higher than the mean biopsy (p-value &lt; 0.001). This group was not associated with age, stage, breast cancer subtype, or regimen. We examined our results in the 37/61 patients who did not achieve pCR. In all breast cancer subtypes, this group had an increase from biopsy to surgery in sTIL, with no significant difference between treatment regimens. Increasing age was significantly associated with lower sTIL in both biopsy and surgery specimens (p-value = 0.033). For every decade increase in age, sTIL decreased by about 37%.
Discussion
Overall the sTIL declined from biopsy to surgery. In the group of patients with an increase in sTIL, there was no significant correlation with systemic treatment regimen. There was a nonsignificant trend towards increasing sTIL and residual disease at surgery. We hypothesize that the host immune response declined after tumor eradication in pCR and remained active when residual disease was present. Increasing age was significantly associated with lower sTIL. Further work to identify additional factors associated with sTIL is needed to guide efforts to alter the immune response for improved breast cancer outcomes.
Citation Format: Armaghani A, Asirvatham R, Mramba L, Daily K. Impact of neoadjuvant systemic therapy on sTIL in breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-05-10.