Prognostic significance of tumour-infiltrating lymphocytes for oestrogen receptor-negative breast cancer without lymph node metastasis

Abstract

Tumour-infiltrating lymphocytes (TILs) are regarded as significant prognostic markers in patients with breast cancer. However, the prognostic utility of TIL expression based on the intrinsic subtypes has just been identified. The present study investigated the relationship between TIL grades and prognosis in 294 Japanese paitents with breast cancer stratified based on the intrinsic subtypes and clinicopathological characteristics. Stromal TIL status was evaluated using haematoxylin and eosin staining, and TIL grades were categorised into low (<10%), intermediate (≥10 and ≤40%) and high (>40%) groups. The relationship between TIL expression and the intrinsic subtypes, clinicopathological characteristics and patient prognosis was analyzed. It was revealed that high TIL expression was correlated with negative oestrogen receptor (ER) expression and high histological grade (P<0.001). Among the ER-negative patients, the relapse-free survival (RFS) rate of the high-grade TIL group was significantly higher than that of the low-grade TIL group (P=0.04). Among the ER-negative patients without lymph node metastasis, RFS and cancer-specific survival (CSS) rates of patients with high-grade TILs were significantly higher than the RFS and CSS rates of patients with low-grade TILs (P=0.01). However, among ER-positive patients, RFS was significantly higher in the low-grade TIL group than in the high-grade TIL group (P=0.02). In conclusion, TIL expression correlated with ER status and tumour proliferation. High TIL expression was a poor prognostic marker in ER-positive patients but was a good prognostic marker in ER-negative patients. Therefore, the biological association between TILs and primary breast tumours may differ between ER-positive and ER-negative breast cancer.

Keywords: breast cancer; lymph node metastasis; oestrogen receptor; prognosis; tumour-infiltrating lymphocytes.

Figure 1.

Classification of tumour-infiltrating lymphocytes (TILs) using the criteria of the International TILs Working Group. (A) Low-grade TILs: A few lymphocytes are present in tissue surrounding the cancer nests. (B) Intermediate-grade TILs. (C) High-grade TILs: Numerous lymphocytes are distributed adjacent to the cancer nests.

Figure 2.

Survival curves of breast cancer subtypes stratified by TIL expression. (A) RFS and (B) CSS curves stratified by TIL expression in HER2-positive patients. (C) RFS and (D) CSS curves stratified by TIL expression in HR-positive and HER2-negative patients. (E) RFS and (F) CSS curves stratified by TIL expression in triple-negative patients. TIL, tumour-infiltrating lymphocyte; RFS, relapse-free survival; CSS, cancer-specific survival; HER2, human epidermal growth factor receptor type 2; HR, hormonal receptor.

Figure 3.

Survival curves stratified by TIL expression and ER status. Comparisons of (A) RFS and (B) CSS between high-grade and low-grade TILs groups in ER-negative patients. The relationship between TIL expression and (C) RFS and (D) CSS in ER-positive breast cancer patients. TIL, tumour-infiltrating lymphocyte; ER, oestrogen receptor; RFS, relapse-free survival; CSS, cancer-specific survival.

Figure 4.

Survival curves stratified by TIL expression and pathological nodal status. Comparisons of (A) RFS and (B) CSS between high-grade and low-grade TIL groups in pathological node-negative patients. The relationship between TIL expression and (C) RFS and (D) CSS in pathological node-positive patients. TIL, tumour-infiltrating lymphocyte; RFS, relapse-free survival; CSS, cancer-specific survival.

Figure 5.

Survival curves stratified by TIL expression and pathological nodal status in ER-negative patients. Comparisons of (A) RFS and (B) CSS between high-grade and low-grade TIL groups in ER-negative and pathological node-negative patients. The relationship between TIL expression and (C) RFS and (D) CSS in ER-negative and pathological node-positive patients. TIL, tumour-infiltrating lymphocyte; ER, oestrogen receptor; RFS, relapse-free survival; CSS, cancer-specific survival.