Higher Stromal Tumor-Infiltrating Lymphocyte Level Associated With Improved Outcome in Triple-Negative Breast Cancer
In an analysis of patients with operable triple-negative breast cancer in two Eastern Cooperative Oncology Group (ECOG) adjuvant trials, Adams and colleagues found that higher stromal compartment tumor-infiltrating lymphocyte levels were associated with significantly improved disease-free survival, distant recurrence–free interval, and overall survival. The findings of the study, reported in the Journal of Clinical Oncology, suggest that trials in this setting should include stratification for stromal lymphocyte infiltration.
Study Details
In the study, hematoxylin and eosin–stained sections of 506 tumors from patients in the randomized ECOG E2197 and E1199 trials were assessed for density of tumor-infiltrating lymphocytes in intraepithelial and stromal compartments. Patients with triple-negative disease were randomly selected from the trial populations based on availability of sections.
Intraepithelial tumor-infiltrating lymphocytes were defined as the percentage of lymphocytes in direct contact with tumor cells and stromal tumor-infiltrating lymphocytes were defined as the percentage of tumor stroma containing infiltrating lymphocytes. In tumor-infiltrating lymphocyte scoring, estimates were rounded up to the next highest decile—eg, a tumor-infiltrating lymphocyte score of 20 was given to a sample with 11% to 20% lymphocytes. The primary outcome measure was association of tumor-infiltrating lymphocyte score with disease-free survival.
Better Outcomes With Higher Stromal Tumor-Infiltrating Lymphocytes
Of 481 evaluable cancers, 80% contained stromal tumor-infiltrating lymphocytes and 15% contained intraepithelial tumor-infiltrating lymphocytes. Median follow-up was 10.6 years. Higher stromal tumor-infiltrating lymphocyte scores were associated with significantly improved outcomes. On univariate analysis, for every 10% increase in stromal tumor-infiltrating lymphocytes, there was a 14% reduction of risk of recurrence or death (hazard ratio [HR] = 0.86, P = .02), 18% reduction of risk of distant recurrence (HR = 0.82, P = .04), and 19% reduction of risk of death (HR = P = .01). The hazard ratio for disease-free survival for presence vs absence of stromal tumor-infiltrating lymphocytes was 0.69 (P = .04).
Improvements in disease-free survival (HR = 0.72, P = .06), distant recurrence–free interval (HR = 0.53, P = .08), and overall survival (HR = 0.64, P = .08) with each 10% increase in intraepithelial tumor-infiltrating lymphocytes and in disease-free survival for presence vs absence of intraepithelial tumor-infiltrating lymphocytes (HR = 0.69, P = .09) did not reach statistical significance.
On multivariate analysis including tumor size, lymph node status, and age, stromal tumor-infiltrating lymphocytes remained an independent predictor of disease-free survival (HR = 0.84, P = .005), distant recurrence–free interval (HR = 0.81, P = .02), and overall survival (HR = 0.79, P = .003).
The investigators concluded, “In two national randomized clinical trials using contemporary adjuvant chemotherapy, we confirm that stromal lymphocytic infiltration constitutes a robust prognostic factor in [triple-negative breast cancers]. Studies assessing outcomes and therapeutic efficacies should consider stratification for this parameter.”
Sylvia Adams, MD, of New York University Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported in part by grants from the National Cancer Institute, sanofi-aventis, and the Breast Cancer Research Foundation. The authors reported no conflicts of interest.
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®.
