Association of tumor infiltrating lymphocytes with pathological response after neoadjuvant therapy in breast cancer: A retrospective study.

Abstract

e12621 Background: Tumor infiltrating lymphocytes (TILs) are thought to represent favorable host anti-tumor immunity and play an important role in mediating response to chemotherapy in breast cancer. TILs are heterogenous across breast cancer subtypes and are increasingly being studied as prognostic and predictive biomarkers. We undertook a retrospective study to establish the relationship between pre-treatment density of TILs and subsequent quality of response to neoadjuvant chemotherapy in patients with early-stage breast cancer. Methods: We retrospectively identified women with breast cancer who had received neoadjuvant therapy (NAT) at the University of Cincinnati from 2012-2018. Clinical and pathological variables were extracted from medical records. Pre-treatment core biopsies were assessed for intra-tumoral TILs through independent pathology review and were graded as mild (grade 1), moderate (grade 2) or severe (grade 3). Post-treatment resection samples were assessed for pathological complete response (pathCR). Univariate analysis was done to determine the association between TILs and pathCR. Results: We identified 148 patients with breast cancer who received NAT, median age 53 years (25-90), 77 were Caucasian. 32 patients had stage I disease at diagnosis, 87 stage II and 29 stage III. Most patients had tumor grade 2 (n=50) or 3 (n=91). 50 patients were HER2+, 65 ER/PR+ HER2- (HR+) and 33 had triple negative breast cancer (TNBC). 69 patients received anthracycline based NAT, 29 non-anthracycline based NAT and all HER2+ patients received anti-HER2 therapy. 72 patients had TILs grade 1, 54 grade 2 and 22 had grade 3. 50 patients achieved pathCR. On univariate analysis grade 2 and 3 TILs were associated with higher likelihood of pathCR compared to grade 1 (42.1% vs 25%, OR 2.18, [1.08 – 4.4], p = 0.029). There was no difference in pathCR between grade 2 and grade 3 TILs (40.7% vs 45.5%, OR 1.21 [0.45-3.29], p=0.12). Tumor grade 3 was associated with higher pathCR than grade 1 or 2 (41.8 vs 21.1%, OR 2.69 [1.26-5.75], p=0.01). Amongst breast cancer subtypes, pathCR was lower in HR+(13.8%) compared to TNBC (45.5%) or HER2+ (52%) with OR 0.15 (0.06-0.36), p<0.01. Age, race, stage and type of chemotherapy were not associated with pathCR. On multivariate analysis, none of the variables retained significance. Conclusions: Our analysis shows that increased TILs density (grade 2 or 3) and higher tumor grade are associated with pathCR whereas HR+ breast cancer have a lower rate of pathCR after NAT. Immune characterization of TILs might be helpful in further refining the prognostic impact of TILs.[Table: see text]