Immune microenvironment and intrinsic subtyping in hormone receptor-positive/HER2-negative breast cancer

Gaia Griguolo,Pierfranco Conte,Giancarlo Bisagni,Enrico Tagliafico,Guido Ficarra,Luigi Cavanna,Maria Vittoria Dieci,Laia Paré,Katia Cagossi,Antonio Frassoldati,Aleix Prat,Federica Miglietta,Valentina Guarneri,Federico Piacentini,Daniele Giulio Generali

doi:10.1038/s41523-021-00223-x

Abstract

Little is known regarding the interaction between immune microenvironment and tumor biology in hormone receptor (HR)+/HER2− breast cancer (BC). We here assess pretreatment gene-expression data from 66 HR+/HER2− early BCs from the LETLOB trial and show that non-luminal tumors (HER2-enriched, Basal-like) present higher tumor-infiltrating lymphocyte levels than luminal tumors. Moreover, significant differences in immune infiltrate composition, assessed by CIBERSORT, were observed: non-luminal tumors showed a more proinflammatory antitumor immune infiltrate composition than luminal ones.

Highlights

Little is known regarding the interaction between immune microenvironment and tumor biology in hormone receptor (HR)+/HER2 − breast cancer (BC)
HR+/HER2− BCs are generally described as immunologically cold tumors, presenting lower levels of tumor-infiltrating lymphocytes (TILs, as evaluated on H&E stained slides4) and PD-L1 (Programmed cell Death protein-Ligand 1)[5,6,7]
In a metanalysis including over 1300 HR+/HER2− BC patients treated with neoadjuvant chemotherapy, high TIL levels were associated with significantly higher rates of pathological complete response and paradoxically with significantly shorter overall survival[5]

Summary

Introduction

Little is known regarding the interaction between immune microenvironment and tumor biology in hormone receptor (HR)+/HER2 − breast cancer (BC). Basal-like) represent a non-negligible fraction (5–30%) of HR +/HER2− BCs and are associated with specific clinical characteristics, such as reduced endocrine sensitivity, increased chemo sensitivity, and poorer outcome, as compared to Luminal-A or Luminal-B counterparts[2,3]. We here assess TIL levels and immune infiltrate composition according to intrinsic subtyping in postmenopausal HR+/HER2− BC patients enrolled in a phase-II randomized neoadjuvant trial of letrozole ± lapatinib (LETLOB trial)[8].

Results

Conclusion