Stromal Tumor-infiltrating Lymphocytes in NRG Oncology/NSABP B-31 Adjuvant Trial for Early-Stage HER2-Positive Breast Cancer

J Natl Cancer Inst. 2019 Aug 1;111(8):867-871. doi: 10.1093/jnci/djz032.

Abstract

We retrospectively assessed association of stromal tumor-infiltrating lymphocytes (sTILs) with clinical outcomes and molecular variables reportedly predictive of trastuzumab-benefit in National Surgical Adjuvant Breast and Bowel Project B-31 (N = 2130). sTILs were assessed in 1581 eligible B-31 cases utilizing all available hematoxylin and eosin slides. Mean concordance between main reviewer and six other pathologists was 90.8% in 100 cases. Cox regressions were used to calculate hazard ratios (HRs). In chemotherapy and trastuzumab added to chemotherapy arms, increases in sTILs, as a semicontinuous variable (combined arms HR = 0.42, 95% confidence interval = 0.27 to 0.64, two-sided P < .001) or as lymphocyte-predominant breast cancer with more than 50% sTILs (combined arms HR = 0.65, 95% confidence interval = 0.49 to 0.86, two-sided P = .003) were statistically significantly associated with improved disease-free survival. There was no association of sTILs with trastuzumab benefit. However, higher sTILs were statistically significantly associated with higher trastuzumab benefit groups by 8-gene prediction model (two-sided P < .001). Neither PIK3CA mutations nor Fc-gamma-receptor polymorphisms were associated with sTILs. sTILs may have utility as a prognostic biomarker identifying HER2-positive early breast cancer at low recurrence risk.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / genetics
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Chemotherapy, Adjuvant / adverse effects
  • Class I Phosphatidylinositol 3-Kinases / genetics*
  • Disease-Free Survival
  • Female
  • Humans
  • Lymphocytes, Tumor-Infiltrating / drug effects
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / pathology
  • Proportional Hazards Models
  • Pyrimidines / therapeutic use
  • Receptor, ErbB-2 / genetics*
  • Receptors, IgG / genetics*
  • Stromal Cells / drug effects
  • Stromal Cells / pathology
  • Trastuzumab / adverse effects
  • Trastuzumab / therapeutic use

Substances

  • Biomarkers, Tumor
  • Pyrimidines
  • Receptors, IgG
  • B 31
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab