Prognostic and predictive impacts of tumor-infiltrating lymphocytes differ between Triple-negative and HER2-positive breast cancers treated with standard systemic therapies

Abstract

Tumor-infiltrating lymphocytes (TILs) have potential value for stratifying the treatment of breast cancer (BC), though their precise use remains unclear. We aimed to investigate the utility of TILs using an alternative approach in different settings. We reviewed patients with triple-negative (TN) or human epithelial growth factor receptor 2 (HER2)-positive invasive ductal carcinomas from a single institutional cohort and classified archived hematoxylin–eosin-stained samples in terms of TIL score as low (<10 %), intermediate, and high (>50 %). The prognostic and predictive values of TILs were analyzed retrospectively in both adjuvant and neo-adjuvant settings. In the adjuvant setting, the presence of TILs at primary surgery was a significant favorable prognostic factor among 154 TNBCs [relapse-free survival (RFS): p = 0.015], but not among 183 HER2+ BCs (RFS: p = 0.097). The TNBC low-TIL group tended to relapse earlier. In the neo-adjuvant setting, detection of TILs on biopsy before primary systemic therapy was associated with the ratio of patients achieving pathological complete response among 48 TNBCs (p = 0.024), but not among 58 HER2+ BCs (p = 0.30). The presence of TILs in surgical specimens after systemic therapy had prognostic value in HER2+ BC (RFS: p = 0.007). The impact of TILs differs between patients with TN and HER2+ BC treated with standard therapies. Our three-grade scale for TILs may contribute to our understanding of the importance of the tumor microenvironment in routine practice. TILs after primary systemic therapy may be useful for the further stratification of treatment of HER2+ BC.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-016-3848-2) contains supplementary material, which is available to authorized users.

Heterogeneity of tumour‐infiltrating lymphocytes in breast cancer and its prognostic significance

“…Intraobserver agreement was determined by use of the Pearson correlation coefficient, and interobserver agreement was determined by use of an intraclass correlation coefficient. TILs scores were categorised with a 10% cut‐off; cases with scores of <10% were defined as negative/low, and cases with scores of ≥10% were defined as positive/high . In recurrent tumours, the median percentage of TILs scores (5%) was used.…”

“…TILs scores were categorised with a 10% cut-off; cases with scores of <10% were defined as negative/low, and cases with scores of ≥10% were defined as positive/high. 4 In recurrent tumours, the median percentage of TILs scores (5%) was used. Positive immunoreactivity for CD3, CD8, CD20, FOXP3 and CD68 was defined as previously described.…”

Immune Blockade Inhibition in Breast Cancer

“…In contrast, high post-treatment TILs had a good prognostic implication after neo-adjuvant treatment in Her2-positive cancers but displayed no statistically significant prognostic value in triple-negative ones. Nevertheless, the four triple-negative patients in the high TILs tier had all remained relapse-free, while eleven of 24 patients in the intermediate and low TILs tiers had relapsed within about 3 years of follow-up (33).…”

“…In a study of TILs in localized triple-negative and Her2-positive breast cancers that used a three tier evaluation system in pathologic slides (high TILs >50%, intermediate 10-50% and low TILs <10%), a high TILs infiltration was associated with a better prognosis in triple-negative patients treated with adjuvant chemotherapy but not in Her2-positive patients (33). In contrast, high post-treatment TILs had a good prognostic implication after neo-adjuvant treatment in Her2-positive cancers but displayed no statistically significant prognostic value in triple-negative ones.…”

Prediction Role of Tumor-Infiltrating Lymphocytes in Triple Negative Breast Cancer Patients Received the Neoadjuvant Chemotherapy: A Meta-Analysis

“…However, the different subtype of breast cancer may own differ impact by TIL and is still complex. We searched studies research the value of TIL for pCR in TNBC who underwent NAC treatment [5][6][7][8][9][10]. Analysis was conducted to find out whether the TIL can be a predictive index for triple negative breast cancer.…”