Association of Stromal Tumor-Infiltrating Lymphocytes With Recurrence-Free Survival in the N9831 Adjuvant Trial in Patients With Early-Stage HER2-Positive Breast Cancer

Abstract

The presence of dense lymphocytic infiltrates in breast carcinoma has long been recognized by breast histopathologists.¹ The term medullary carcinoma was first used in 1949 to describe a high-grade breast carcinoma growing in anastomosing sheets composed of large cells with numerous mitoses and an “intimate” stromal lymphoid infiltrate that was associated with a better-than-average prognosis.¹ The association of dense stromal lymphocytic infiltrates characteristic of medullary carcinoma and a good prognosis continued to be documented throughout the 20th century; however, the etiology of this better prognosis remained uncertain.^2-4 Medullary carcinomas are by definition estrogen receptor negative. Microarray-based comparative genomic hybridization studies examining the enriched tumor DNA of medullary carcinoma show that medullary breast carcinomas share common genomic alterations with basal-like carcinomas, the most frequent being 1q and 8q gains and X losses. However, medullary breast carcinomas appear to be a distinct entity within the basal-like spectrum characterized by higher proportions of genome copy number aberrations than basal carcinomas and recurrent 10p, 9p, and 16q gains, 4p losses, and 1q, 8p, 10p, and 12p amplicons and, most importantly, are associated with better prognosis.^5,6