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Association of Tumor-Infiltrating Lymphocytes With Prognosis in Breast Cancer Subtypes

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Key Points

  • Increased TILs were associated with increased likelihood of pathologic complete response in all subtypes examined.
  • Increased TILs were associated with better prognosis in triple-negative breast cancer and HER2-positive breast cancer but poorer outcome in luminal HER2-negative disease.

In a study reported in The Lancet Oncology by Denkert et al, increased levels of tumor-infiltrating lymphocytes (TILs) in women receiving neoadjuvant chemotherapy were associated with improved prognosis in HER2-positive breast cancer and triple-negative breast cancer, but poorer outcome in luminal HER2-negative breast cancer.

Study Details

The study involved 3,771 women from six 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 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.”

The study was funded by Deutsche Krebshilfe and the European Commission.

Carsten Denkert, MD, of Institut fur Pathologie, Charité Universitätsmedizin Berlin, is the corresponding author for The Lancet Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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