Tumor-Infiltrating Lymphocytes and Prognosis in Breast Cancer Subtypes

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In a study reported in The Lancet Oncology by Denkert and colleagues, increased levels of tumor-infiltrating lymphocytes (TILs) in women receiving neoadjuvant chemotherapy were associated with improved prognosis in HER2-positive and triple-negative breast cancers but poorer outcome in luminal HER2-negative breast cancer. Carsten Denkert, MD, of Institut fur Pathologie, Charité Universitätsmedizin Berlin, is the corresponding author of The Lancet Oncology article. 

The study involved 3,771 women from 6 German Breast Cancer Group randomized trials with pretherapeutic core biopsies. TILs were analyzed both as a continuous parameter and in three predefined groups of low (0%–10% immune cells in stromal tissue within the tumor), intermediate (11%–59%), and high TILs (≥ 60%). Survival data came from 2,560 patients in 5 of the 6 trials. 

Association With Outcomes 

According to low, intermediate, and high TIL groups, pathologic complete response was observed in 6%, 11%, and 28% of patients with the luminal HER2-negative subtype; 32%, 39%, and 48% of those with the HER2-positive subtype; and 31%, 31%, and 50% of those with triple-negative breast cancer (P < .0001 for trend in each subtype). 

A 10% increase in TILs was associated with longer disease-free survival in triple-negative breast cancer (hazard ratio [HR] = 0.93, P = .011) and HER2-positive breast cancer (HR = 0.94, P = .017) but not in luminal HER2-negative disease (HR = 1.02, P = .46). A 10% increase was associated with longer overall survival in triple-negative breast cancer (HR = 0.92, P = .032), nonsignificantly longer survival in HER2-positive breast cancer (HR = 0.94, P = .11), and shorter survival in luminal HER2-negative disease (HR = 1.10, P = .011). 

The investigators concluded: “Increased TIL concentration predicted response to neoadjuvant chemotherapy in all molecular subtypes assessed and was also associated with a survival benefit in HER2-positive breast cancer and triple-negative breast cancer. By contrast, increased TILs were an adverse prognostic factor for survival in luminal HER2-negative breast cancer, suggesting a different biology of the immunological infiltrate in this subtype. Our data support the hypothesis that breast cancer is immunogenic and might be targetable by immune-modulating therapies. In light of the results in luminal breast cancer, further research investigating the interaction of the immune system with different types of endocrine therapy is warranted.” ■

Denkert C, et al: Lancet Oncol 19:40-50, 2018. 




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