Stromal Tumor–Infiltrating Lymphocytes and Outcomes in Early-Stage HER2-Positive Breast Cancer


Key Points

  • Higher sTILs were associated with improved disease-free survival in the combined trastuzumab plus chemotherapy and chemotherapy groups.
  • Higher sTILs were not associated with degree of trastuzumab benefit in the trial.  

In a study reported in the Journal of the National Cancer Institute, Kim and colleagues found that higher levels of stromal tumor–infiltrating lymphocytes (TILs) were associated with better outcomes in patients receiving adjuvant chemotherapy or trastuzumab plus chemotherapy for early-stage HER2-positive breast cancer in the NRG Oncology/NSABP B-31 trial, but were not associated with the degree of trastuzumab benefit in the trial.

The study involved the assessment of stromal TILs in 1,581 eligible cases from the NSABP B-31 trial (n = 2,130) using all evaluable hematoxylin-and-eosin slides. The effect of stromal TILs on outcome was assessed as a semicontinuous variable and as lymphocyte-predominant breast cancer with > 50% stromal TILs. The mean concordance on stromal TIL levels between a main reviewer and 6 other pathologists was 90.8% in 100 cases.

Stromal TILs and Outcome

For the combined trastuzumab-plus-chemotherapy and chemotherapy groups, increases in stromal TILs were associated with significantly improved disease-free survival both as a semicontinuous variable (hazard ratio [HR] = 0.42, P < .001) or as lymphocyte-predominant disease with > 50% stromal TILs (HR= 0.65, P = .003). However, there was no association of stromal TILs with the degree of trastuzumab benefit in analysis as a semicontinuous variable (interaction P = .65) or when dichotomized by level > 50% (interaction P = .50).

Despite the absence of association with stromal TIL levels alone and trastuzumab benefit, higher stromal TIL levels were significantly associated with predicted trastuzumab-benefit groups on the 8-gene trastuzumab-benefit prediction model; higher levels of stromal TILs were associated with high- and medium-benefit groups on the 8-gene model (P < .001). No association of stromal TILs with PIK3CA mutation or Fc-gamma receptor polymorphisms was observed.

The investigators concluded, “[Stromal] TILs may have utility as a prognostic biomarker identifying HER2-positive early [breast cancer] at low recurrence risk.”

Katherine L. Pogue-Geile, PhD, of NSABP/NRG Oncology, Department of Pathology, Pittsburgh, is the corresponding author for the Journal of the National Cancer Institute article.

Disclosure: The study was supported by grants from the National Cancer Institute, Pennsylvania Department of Health, and Breast Cancer Research Foundation. The study authors’ full disclosures can be found at

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