SUV39H1 Expression as a Guideline for Omitting Radiotherapy in Lymph Node-positive Triple-negative Breast Cancer Patients

Abstract

Background/Aim: The role of postoperative radiotherapy (RT) combined with chemotherapy (CT) for lymph node-positive (LN+) triple-negative breast cancer (TNBC) remains controversial. SUV39H1-mediated epigenetic regulation is associated with cancer cell migration, invasion, metastasis, and treatment resistance. This study aims to identify the role of SUV39H1 in TNBCs. Materials and Methods: Overall, 498 TNBCs with SUV39H1 RNA-seq profiles were retrieved from TCGA-BRCA and analyzed; the X-tile algorithm was used to stratify the population into low, intermediate, and high SUV39H1. Furthermore, we performed an in vitro clonogenic cell survival assay using the MDA-MB-231 cell line to assess the effects of SUV39H1 on cellular responses. Results: The results showed that SUV39H1 was significantly higher in TNBC than normal tissue and luminal subtype breast cancer. Notably, SUV39H1 is significantly expressed in the basallike 1 (BL1) and immunomodulatory (IM) subgroups, compared to other subtypes. Compared to patients with a low or medium expression of SUV39H1, omitting RT only worsens disease-free survival (DFS) in those with high SUV39H1 expression. The experimental results showed SUV39H1 was suppressed by si-SUV39H1, and SUV39H1 knockdown in MDA-MB-231-IV2-1 cells enhanced the cellular toxicity of doxorubicin and paclitaxel. Conclusion:Targeting SUV39H1 may provide a potential guiding indication of omitting RT to avoid over-treatment and chemosensitivity for TNBC.Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and is characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. Because these three receptors are lacking, TNBC is resistant to hormone therapy and HER2-targeted therapy, significantly reducing treatment options. Studies have shown that TNBCs have high local recurrence and distant metastasis rates (1, 2). TNBC also accounts for ~67% of all breast cancer deaths while present in 10-20% of cases only (3). The specific pathophysiology of TNBC remains poorly explored. Hence, studies are focused on identifying suitable targets to predict outcomes for clinical decision-making and enhance the effect of therapies on TNBC.The standard care for TNBC is a multidisciplinary approach involving surgery, chemotherapy (CT), and 582