Gene Expression Profiling in Early Breast Cancer-Patient Stratification Based on Molecular and Tumor Microenvironment Features

Gyöngyi Munkácsy; Libero Santarpia; Balázs Győrffy

doi:10.3390/biomedicines10020248

Gene Expression Profiling in Early Breast Cancer-Patient Stratification Based on Molecular and Tumor Microenvironment Features

Biomedicines. 2022 Jan 24;10(2):248. doi: 10.3390/biomedicines10020248.

Authors

Gyöngyi Munkácsy^{1

2}, Libero Santarpia³, Balázs Győrffy^{1

4}

Affiliations

¹ TTK Cancer Biomarker Research Group, Institute of Enzymology, Magyar Tudósok Körútja 2, 1117 Budapest, Hungary.
² 2nd Department of Pediatrics, Semmelweis University, Tűzoltó Utca 7-9, 1094 Budapest, Hungary.
³ Seagen, Dammstrasse 23, 6300 Zug, Switzerland.
⁴ Department of Bioinformatics, Semmelweis University, Tűzoltó Utca 7-9, 1094 Budapest, Hungary.

Abstract

Patients with early-stage hormone receptor-positive, human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) are typically treated with surgery, followed by adjuvant systemic endocrine therapy with or without adjuvant chemotherapy and radiation therapy. Current guidelines regarding the use of adjuvant systemic therapy depend on clinical and pathological factors, such as the morphological assessment of tumor subtype; histological grade; tumor size; lymphovascular invasion; and lymph node status combined with estrogen receptor, progesterone receptor, and HER2 biomarker profiles assessed using immunohistochemistry and in situ hybridization. Additionally, the prognostic and predictive value of tumor-infiltrating lymphocytes and their composition is emerging as a key marker in triple negative (TNBC) and HER2-enriched molecular breast tumor subtypes. However, all these factors do not necessarily reflect the molecular heterogeneity and complexity of breast cancer. In the last two decades, gene expression signatures or profiling (GEP) tests have been developed to predict the risk of disease recurrence and estimate the potential benefit of receiving adjuvant systemic chemotherapy in patients with luminal breast cancer. GEPs have been utilized to help physicians to refine decision-making process, complementing clinicopathological parameters, and can now be used to classify the risk of recurrence and tailoring personalized treatments. Several clinical trials using GEPs validate the increasing value of such assays in different clinical settings, addressing relevant clinical endpoints. Finally, the recent approval of immune checkpoint inhibitors in TNBC and the increasing use of immunotherapy in different molecular BC populations highlight the opportunity to refine current GEPs by including a variety of immune-related genes that may help to improve predicting drug response and finetune prognosis.

Keywords: adjuvant chemotherapy; classification; early breast cancer; gene expression profiling; immune-related genes; predictive; prognosis.

Publication types

Review