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High tumor-infiltrating lymphocyte levels (>40%) predicted improved survival in triple-negative breast cancer, emphasizing TILs as a key prognostic biomarker.
Triple-negative breast cancer is an aggressive subtype of breast cancer characterized by the absence of estrogen and progesterone receptor expression and lack of HER2 amplification. Tumor-infiltrating lymphocytes (TILs) have emerged as a biomarker with prognostic and predictive value in triple-negative breast cancer, according to authors of an abstract presented at the 2024 San Antonio Breast Cancer Symposium.
“TILs are promising, inexpensive biomarker with prognostic and predictive potential in triple-negative breast cancer. There is no consensus on the appropriate cutoff point to define high and low TILs,” wrote Petr Krivorotko, MD, PhD, and colleagues. “Therefore, we aimed to evaluate the prognostic value of TILs in an independent triple-negative breast cancer cohort and to determine an appropriate cut-off point by which to stratify TILs scores into prognostically significant categories.”
Stratifying Patients by TIL Levels
The researchers analyzed 140 patients with stage 1-3 triple-negative breast cancer and estrogen receptor expression below 10%. The investigators assessed baseline tumor tissue samples for histological type, HER2 expression, estrogen receptor levels, Ki-67 index, and TIL levels.
The researchers evaluated pathological response with the ypTNM, Miller-Payne, and Residual Cancer Burden classifications. TIL levels were categorized into low (<10%), intermediate (10% to 40%), and high (>40%) groups based on the International Working Group’s guidelines. For further analysis, the researchers used a binary system to classify TILs as low (≤40%) or high (>40%).
Event-free survival (EFS) rates were compared using the Kaplan-Meier method and Cox regression.
Evaluating the Link With Prognosis
The average baseline TIL level in the cohort was 29.3%. The researchers found low TIL levels in 21% of cases, intermediate levels in 55%, and high levels in 24%. When the binary classification was applied, low TIL levels accounted for 76%, while high levels represented 24%.
Correlation analysis revealed a significant association between TIL levels and histological grade (R, 0.187; P=0.027) as well as estrogen receptor expression (R, 0.211; P=0.012). However, the researchers found no significant correlations between TIL levels and other pathological parameters.
The prognostic impact of TIL levels on EFS was significant in the binary classification. Patients with high TIL levels demonstrated a 3-year EFS rate of 95%, compared with 65% in those with low TIL levels (HR, 0.119; 95% CI, 0.02–0.88; P=0.037). When categorized into three groups, the 3-year EFS rates were 64% for low, 65% for intermediate, and 95% for high TIL levels. However, the differences in EFS between low and intermediate TIL groups did not reach statistical significance (HR, 0.386; 95% CI, 0.10–1.44; P=0.156).
The authors concluded that patients with high TIL levels experienced significantly better 3-year EFS rates compared with those with low TIL levels.
“Stromal TILs are an important prognostic biomarker in triple-negative breast cancer. Using a cutoff of 40%, high TILs are significantly associated with longer EFS,” Petr Krivorotko and colleagues said.