The therapeutic potential of circular RNA in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is among the most aggressive subtypes of the disease that does not express estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Circular RNAs (circRNAs) are a type of non-coding RNA with a circular shape formed by non-standard splicing or reverse splicing. Numerous circRNAs exhibit abnormal expression in various malignancies, showing their critical role in the emergence and growth of tumors. Recent studies have shown evidence supporting the idea that certain circRNAs regulate the proliferation and metastasis of TNBC. In addition, circRNAs alter metabolism and the immune microenvironment to promote or inhibit the development of TNBC. Notably, circRNAs may affect the efficacy of clinical drug therapy, serve as therapeutic targets, and be used as molecular biomarkers in the future. Herein, we will first summarize the biogenesis and function of circRNAs. Then, we will explain current research on circRNAs related to TNBC and their potential to serve as therapeutic targets or biomarkers for future drug development, providing a new direction and idea for TNBC therapy.

Survival differences between HER2-0 and HER2-low-expressing breast cancer - A meta-analysis of early breast cancer patients.

BACKGROUND: HER2-low (human epidermal growth factor receptor 2) breast cancer takes up 40-50% in all breast cancer subtypes. The survival difference between HER2-low and HER2-zero breast cancers remain uncertain. Therefore, the aim of this study was to compare survival outcome of the two subtypes and to explore the impact of hormone receptor status. METHODS: A comprehensive medical literature search was performed by searching PubMed, EMBASE, and the Cochrane Libraries up to August 2022. We included observational studies reporting hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). The results of individual studies were pooled by random-effects models using Stata 16.0. Seventeen articles with a total of 78984 breast cancer patients were included in the meta-analysis. RESULTS: We observed a statistically significant association between low HER2 expression and better breast cancer survival outcomes (OS: HR: 0.83; 95% confidence interval: 0.75, 0.90; DFS/RFS: HR: 0.83; 95% confidence interval: 0.75, 0.91). In a subgroup analysis, we found that HER2-low patients had better survival outcomes relative to hormone receptor-positive breast cancer patients (OS: HR: 0.87; 95% confidence interval: 0.81, 0.93; DFS/RFS: HR: 0.91; 95% confidence interval: 0.85, 0.96). Similarly, in triple-negative breast cancer patients, we also observed a positive association between HER2 low expression and better survival (OS: HR: 0.85; 95% confidence interval: 0.71, 0.98; DFS/RFS: HR: 0.85; 95% confidence interval: 0.74, 0.95). CONCLUSIONS: Our study showed that HER2-low breast cancer had better survival outcomes compared to HER2 negative breast cancer in patients with early stage breast cancer, regardless of hormone receptor status. REGISTRATION: This meta-analysis was registered with PROSPERO (CRD42022335704) on June 10, 2022. AVAILABILITY OF DATA AND MATERIALS: All data generated or analysed during this study are included in this published article [and its supplementary information files].

Tumor Microenvironment Characterization in Breast Cancer Identifies Prognostic and Neoadjuvant Chemotherapy Relevant Signatures.

Immune response which involves distinct immune cells is associated with prognosis of breast cancer. Nonetheless, less study have determined the associations of different types of immune cells with patient survival and treatment response. In this study, A total of 1,502 estrogen receptor(ER)-negative breast cancers from public databases were used to infer the proportions of 22 subsets of immune cells. Another 320 ER-negative breast cancer patients from Guangdong Provincial People's Hospital were also included and divided into the testing and validation cohorts. CD8+ T cells, CD4+ T cells, B cells, and M1 macrophages were associated with favourable outcome (all p <0.01), whereas Treg cells were strongly associated with poor outcome (p = 0.005). Using the LASSO model, we classified patients into the stromal immunotype A and B subgroups according to immunoscores. The 10 years OS and DFS rates were significantly higher in the immunotype A subgroup than immunotype B subgroup. Stromal immunotype was identified as an independent prognostic indicator in multivariate analysis in all cohorts and was also related to pathological complete response(pCR) after neoadjuvant chemotherapy. The nomogram that integrated the immunotype and clinicopathologic features showed good predictive accuracy for pCR and discriminatory power. The stromal immunotype A subgroup had higher expression levels of immune checkpoint molecules (PD-L1, PD-1, and CTLA-4) and cytokines (IL-2, INF-γ, and TGF-ß). In addition, patients with immunotype A and B diseases had distinct mutation signatures. Therefore, The stromal immunotypes could predict survival and responses of ER-negative breast cancer patients to neoadjuvant chemotherapy.