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.
Highlights
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
Early-stage breast cancer (BC) patients with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2−) disease are classically treated with surgery, followed by adjuvant endocrine therapies with or without adjuvant chemotherapy (CT) and radiation treatment
A different study reported the presence of 293 overexpressed genes in stroma-enriched core biopsies, including five highly co-expressed metagenes corresponding to different immune functions and extracellular matrix features demonstrating that a B-cell/plasma cell metagene involving the expression of several immunoglobulin genes was associated with prognosis in Estrogen receptor (ER)+ tumors with high proliferative rates, but had lower prognostic impact in ER−, and no prognostic value in patients with ER+ tumor with low proliferation activity [47]
Summary
Early-stage breast cancer (BC) patients with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2−) disease are classically treated with surgery, followed by adjuvant endocrine therapies with or without adjuvant chemotherapy (CT) and radiation treatment. For HR+/HER2−/luminal B-like tumors, the use of CT is contingent on the expression of hormonal receptors (estrogen/progesterone), proliferative markers (Ki67 expression), tumor burden, genomically-assessed risk, and/or patient preference [1]. The additional information provided by multi-gene profiling tests has the capability to advance the accuracy of prognosis and improve risk stratification, identifying patients with a low risk of tumor recurrence, for whom the use of adjuvant CT is not reasonable [4]. GEP assays tend to correlate with other pathologic features of ER+ tumors like proliferation and grade but providing a more robust reproducible test and independent evidence [6]. We evaluate the current evidence of using GEP in clinic and explore and discuss the increasing importance of immune parameters and the possibility to refine current tools with additional immune-GEPs that may help to refine prognosis and provide better predictive tools for early-stage breast cancer
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