Breast cancer is the most frequently diagnosed cancer in women, accounting for 30% of new diagnosing female cancers. Emerging evidence suggests that ubiquitin and ubiquitination played a role in a number of breast cancer etiology and progression processes. As the primary deubiquitinases in the family, ubiquitin-specific peptidases (USPs) are thought to represent potential therapeutic targets. The role of ubiquitin and ubiquitination in breast cancer, as well as the classification and involvement of USPs are discussed in this review, such as USP1, USP4, USP7, USP9X, USP14, USP18, USP20, USP22, USP25, USP37, and USP39. The reported USPs inhibitors investigated in breast cancer were also summarized, along with the signaling pathways involved in the investigation and its study phase. Despite no USP inhibitor has yet been approved for clinical use, the biological efficacy indicated their potential in breast cancer treatment. With the improvements in phenotypic discovery, we will know more about USPs and USPs inhibitors, developing more potent and selective clinical candidates for breast cancer.

Background: The most frequent malignant tumor in women is breast cancer (BRCA). It has been discovered that T-cell exhaustion and macrophages play significant roles in BRCA. It was necessary to explore prognostic genes associated with T-cell exhaustion and macrophage polarization in BRCA.Methods: The following data were included: 35 macrophage polarization-related genes (MPRGs), 683 T-cell exhaustion-related genes (TEXRGs), GSE20685, as well as TCGA-BRCA. Initially, candidate genes were identified through crossing differentially expressed genes (DEGs) obtained by differential expression analysis, key module genes associated with MPRGs, as well as TEXRGs. Next, 101 combinations of 10 machine learning algorithms and univariate Cox analysis were utilized to screen for prognostic genes. Concurrently, a risk model was built for validation in TCGA-BRCA and GSE20685. Next, we conducted immune infiltration, immunotherapy, mutation analysis, molecular regulatory network, as well as drug sensitivity between the two risk groups. Ultimately, we did the reverse transcription-quantitative polymerase chain reaction (RT-qPCR).Results: According to random survival forest (RSF) algorithm (the best combination with the greatest C-index of 0.799), 7 prognostic genes were selected, which are PGK1, BTG2, TANK, CFB, EIF4E3, TNFRSF18, and BATF. After that, we created a risk model, and in the low-risk samples, there was a relatively high survival rate. Next, between two risk parts, the 7 differential immune cells were found. There was a significant difference in 25 immunological checkpoint (ICI) genes between the two risk parts. Next, a lncRNAs-miRNA-mRNA network with 65 nodes and 70 edges was built. Additionally, 84 medications were shown to differ significantly between the two risk groups. Finally, the expression of BTG2, TANK, and EIF4E3 was verified by RT-PCR, which was consistent with the bioinformatics analysis.Conclusion: The 7 prognostic genes (PGK1, BTG2, TANK, CFB, EIF4E3, TNFRSF18, and BATF) were screened, providing new insights into potential treatments for BRCA.

Background: Real-world data of Palbociclib are insufficient in China. This study aimed to investigate the treatment pattern and real-world outcomes in hormone receptor positive and human epidermal growth factor 2 receptor negative (HR+/HER2-) metastatic breast cancer (MBC) patients treated with Palbociclib in the northwest of China. Methods: HR+/HER2- MBC patients who received Palbociclib in 8 centers from July 2017 to September 2019 were retrospectively included in this study. Real-world objective response rate (ORR), progression-free survival (PFS) and safety profiles were analyzed. The survival curves were plotted by the Kaplan-Meier method to analyze PFS, which was verified by the log-rank test. Results: In total, 211 women were eligible for the analysis. A total of 85 patients (40.3%), 78 (37.0%), and 48 (22.7%) received Palbociclib in the first-, second-, third- or later-line setting, respectively. 46 patients achieved partial response and 145 patients experienced stable disease, with an ORR of 21.8% and a disease control rate of 90.5%. Following a median follow-up period of 14.2 months, the median PFS was 12.2 months (95% confidence interval, 10.1-14.3 m), and the median overall survival was not reached. Early Palbociclib initiation, sensitivity or acquired resistance to endocrine therapy, estrogen receptor and progesterone receptor double positivity, less than 3 metastatic sites, without visceral metastasis, bone metastasis only, without prior chemotherapy or endocrine therapy were associated with a prolonged PFS in MBC (All P < 0.05). The most common grade 3 or 4 adverse events (AE) was neutropenia (36.5%), and the most common nonhematologic AE was fatigue (10.9%). No patient experienced AE leading to treatment discontinuation. Conclusion: Palbociclib plus endocrine therapy exhibited favorable effectiveness and manageable toxicities in the real-world setting, supporting their use in Chinese patients with HR+/HER2 − MBC.