Breast cancer (BC) incidence and mortality vary significantly across countries, highlighting the need to update the global burden of female BC, including current trends and future projections. Data were sourced from GLOBOCAN 2022, including estimated new cases and deaths from BC across 21 United Nation (UN) regions and 185 countries, the age-standardized incidence rate (ASIR) and mortality rate (ASMR), the estimated annual percentage changes (EAPC), and demographic projections through 2050. The region-specific and country-specific BC burden for women of all ages and for young women (< 40 years old) was reorganized and re-plotted to highlight subgroup differences. Linear regression was used to explore the link between ASIR/ASMR and the human development index (HDI). Transitioning countries referred to those with low or medium HDI, while transitioned countries were those with high or very high HDI. In 2022, an estimated 2.3 million new BC cases and 666,000 BC-related deaths occurred globally, accounting for 23.8 % and 15.4 % of all cancer cases and deaths in women, respectively. Regionally, Eastern Asia reported the highest number of cases (480,019, ASIR: 37.54/100,000), while South-Central Asia had the highest number of deaths (135,348, ASMR: 13.41/100,000). At the country level, China had the highest number of cases due to its large population, whereas India reported the highest number of deaths. ASIR for both overall and early-onset BC increased with HDI, while ASMR for early-onset BC decreased with HDI (P < 0.05). Overall BC showed an increasing trend in ASIR during 2003–2015 (EAPC: 0.92 %) and a decreasing trend in ASMR during 2006–2016 (EAPC:-1.06 %). Early-onset BC showed a more significant rise in ASIR (EAPCs: 1.4 %) and a slight increase in ASMR (EAPCs: 0.16 %). If national rates remain stable, BC cases and deaths will increase by 54.7 % and 70.9 %, respectively, by 2050. Notably, increased early-onset BC cases are only observed in transitioning countries, while decreased cases are seen in transitioned countries. Breast cancer remains the leading cancer burden in women, particularly in transitioning countries. Addressing this growing burden requires urgent integration of primary prevention, early detection and high-quality treatment through multi-sectoral collaboration.

The impact of breast carcinoma and genital tract malignancy on the physical and mental health, especially reproductive function, of women aged 15-39 years in the adolescent and young adult (AYA) group is significant. This research aims to analyze the burden of AYA female cancer in various regions and countries globally from 1990 to 2021. Epidemiological data were sourced from the Global Burden of Disease (GBD) study 2021. The study analyzed data on female cancers (breast, ovarian, uterine, and cervical) to assess disease burden across different ages, years, and locations, encompassing 21 GBD regions, 195 countries, and five sociodemographic index (SDI) regions. In 2021, AYA female cancer saw 383 241 new cases and 81 679 deaths globally, with 2 975 183 prevalent cases and 4 855 780 disability-adjusted life years. In 2021, Central Latin America recorded the highest age-standardized incidence (ASIR) and prevalence rates (ASPR), whereas South sub-Saharan Africa had the highest age-standardized mortality (ASMR) and disability rates (ASDR). Nations with high SDI typically exhibited elevated ASIR and ASPR, whereas ASMR and ASDR demonstrated inverse patterns. Over the past three decades, ASIR and ASPR of female cancers among AYA women have increased globally. In contrast, the ASMR and ASDR have demonstrated a declining trend. Notably, breast cancer emerged as the most prevalent malignancy among AYA women. Over the past three decades, the ASIR and ASPR of AYA female cancers have consistently increased, significantly burdening this demographic. Additionally, pronounced disparities are evident across different regions and countries, with AYA women in low SDI environments experiencing poorer prognoses compared to their counterparts in high SDI environments. Consequently, it is imperative to enhance interregional collaboration and communication to optimize the overall prognosis of AYA female cancers.

TNBC is characterized by high incidence of visceral metastasis and lacks effective clinical targets. This study aims to delineate the molecular mechanisms of SENP1 in TNBC invasion and metastasis. By using IHC to test the SENP1 expression in TNBC tissues, we analyzed the relationship between SENP1 expression and TNBC prognosis. We showed that SENP1 expression was higher in TNBC tumor tissues and related to TNBC prognosis, supporting SENP1 as an independent risk factor. High expression of SENP1 was significantly associated with histologic grade and tumor lymph node invasion. Intriguingly, the expression levels of SENP1 in TNBC tumors were significantly correlated with that of CSN5, GATA1 and ZEB1. Importantly, SENP1 promoted TNBC cell migration and invasion by regulating ZEB1 deubiquitination and expression through CSN5. Further studies showed that deSUMOylation at lysine residue K137 of GATA1 enhanced the binding of GATA1 to the CSN5 promoter and transactivated CSN5 expression. In addition, we showed that ZEB1 is deubiquitinated at lysine residue K1108. Our in vivo studies also indicated that reduction in SENP1 expression upregulated GATA1 SUMOylation, and thus resulted in decreased expression of CSN5 and ZEB1 in the tumor microenvironment, which decelerated TNBC progression and metastasis. SENP1 promoted CSN5-mediated ZEB1 protein degradation via deSUMOylation of GATA1, and thus influenced TNBC progression. These findings suggest that SENP1 could be utilized as a potential target for blockade of TNBC development and thus provide a totally new approach for TNBC treatment.

Triple-negative breast cancer (TNBC) is a type of breast cancer with poor prognosis, which is prone to distant metastasis and therapy resistance. The presence of neutrophil extracellular traps (NETs) contributes to the progression of breast cancer and is an efficient predictor of TNBC. We obtained the bulk and single-cell RNA sequencing data from public databases. Firstly, we identified five NET-related genes and constructed NET-related subgroups. Then, we constructed a risk index with three pivotal genes based on the differentially expressed genes between subgroups. Patients in the high-risk group had worse prognosis, clinicopathological features, and therapy response than low-risk group. Functional enrichment analysis revealed that the low-risk group was enriched in Wnt signaling pathway, and surprisingly, the drug sensitivity prediction showed that Wnt signaling pathway inhibitors had higher drug sensitivity in the low-risk group. Finally, verification experiments in vitro based on MDA-MB-231 and BT-549 cells showed that tumor cells with low-risk scores had less migration, invasion, and proliferative abilities and high drug sensitivity to Wnt signaling pathway inhibitors. In this study, multi-omics analysis revealed that genes associated with NETs may influence the occurrence, progression, and treatment of TNBC. Moreover, the bioinformatics analysis and cell experiments demonstrated that the risk index could predict the population of TNBC likely to benefit from treatment with Wnt signaling pathway inhibitors.

Breast cancer is one of the most prevalent and diverse malignancies, and, with global cases increasing, the need for biomarkers to inform individual sensitivity to chemotherapeutics has never been greater. Our retrospective clinical analysis predicted that the expression of the fragile site-associated tumor suppressor (FATS) gene was associated with the sensitivity of breast cancer to neoadjuvant chemotherapy with paclitaxel. In vitro experiments subsequently demonstrated that FATS significantly increased the inhibitory effects of paclitaxel on breast cancer cells’ migration, growth, and survival. An interaction screen revealed that FATS interacted with MYH9 and promoted its degradation via the ubiquitin-proteasome pathway, thereby downregulating Wnt signaling. By overexpressing FATS and MYH9, we demonstrated that FATS enhanced paclitaxel-induced apoptosis in breast cancer cells by degrading MYH9 to downregulate the Wnt pathway. We also demonstrated in a mouse xenograft model that FATS significantly increased the chemosensitivity of breast cancer cells to paclitaxel in vivo. This study presents a new mechanism by which FATS interacts with MYH9 to suppress the Wnt/β-catenin signaling pathway and induce apoptosis, thus enhancing the sensitivity of breast cancer cells to paclitaxel chemotherapy. The results also propose novel biomarkers for predicting breast cancer sensitivity to neoadjuvant chemotherapy with paclitaxel. Finally, we provide in vivo evidence that the combination of paclitaxel with IWR-1, a novel Wnt pathway inhibitor, synergistically suppresses breast cancer growth, laying the foundation for future trials with this drug combination. These results therefore provide a number of potential solutions for more precise treatment of patients with breast cancer in the future.

Basal breast cancer subtype is the worst prognosis subtypes among all breast cancer subtypes. Recently, a new tumor stemness index-mRNAsi is found to be able to measure the degree of oncogenic differentiation of tissues. The mRNAsi involved in a variety of cancer processes is derived from the innovative application of one-class logistic regression (OCLR) machine learning algorithm to the whole genome expression of various stem cells and tumor cells. However, it is largely unknown about mRNAsi in basal breast cancer. Here, we find that basal breast cancer carries the highest mRNAsi among all four subtypes of breast cancer, especially 385 mRNAsi-related genes are positively related to the high mRNAsi value in basal breast cancer. This high mRNAsi is also closely related to active cell cycle, DNA replication, and metabolic reprogramming in basal breast cancer. Intriguingly, in the 385 genes, TRIM59, SEPT3, RAD51AP1, and EXO1 can act as independent protective prognostic factors, but CTSF and ABHD4B can serve as independent bad prognostic factors in patients with basal breast cancer. Remarkably, we establish a robust prognostic model containing the 6 mRNAsi-related genes that can effectively predict the survival rate of patients with the basal breast cancer subtype. Finally, the drug sensitivity analysis reveals that some drug combinations may be effectively against basal breast cancer via targeting the mRNAsi-related genes. Taken together, our study not only identifies novel prognostic biomarkers for basal breast cancers but also provides the drug sensitivity data by establishing an mRNAsi-related prognostic model.