Aerobic glycolysis has been recognized as a hallmark of human cancer. G protein pathway suppressor 2 (GPS2) is a negative regulator of the G protein-MAPK pathway and a core subunit of the NCoR/SMRT transcriptional co-repressor complex. However, how its biological properties intersect with cellular metabolism in breast cancer (BC) development remains poorly elucidated. Here, we report that GPS2 is low expressed in BC tissues and negatively correlated with poor prognosis. Both in vitro and in vivo studies demonstrate that GPS2 suppresses malignant progression of BC. Moreover, GPS2 suppresses aerobic glycolysis in BC cells. Mechanistically, GPS2 destabilizes HIF-1α to reduce the transcription of its downstream glycolytic regulators (PGK1, PGAM1, ENO1, PKM2, LDHA, PDK1, PDK2, and PDK4), and then suppresses cellular aerobic glycolysis. Notably, receptor for activated C kinase 1 (RACK1) is identified as a key ubiquitin ligase for GPS2 to promote HIF-1α degradation. GPS2 stabilizes the binding of HIF-1α to RACK1 by directly binding to RACK1, resulting in polyubiquitination and instability of HIF-1α. Furthermore, amino acid residues 70-92 aa of the GPS2 N-terminus bind RACK1. A 23-amino-acid-long GPS2-derived peptide was developed based on this N-terminal region, which promotes the interaction of RACK1 with HIF-1α, downregulates HIF-1α expression and significantly suppresses BC tumorigenesis in vitro and in vivo. In conclusion, our findings indicate that GPS2 decreases the stability of HIF-1α, which in turn suppresses aerobic glycolysis and tumorigenesis in BC, suggesting that targeting HIF-1α degradation and treating with peptides may be a promising approach to treat BC.

Concurrent infection in breast cancer patients is the direct cause of the high mortality rate of the disease. However, there is no available method to increase the survival rate until now. To address the problem, we propose one drug with two target strategy to treat the refractory disease. A small chemical, ph-ph+, was attempted to be used in the study to explore the feasibility of the approach in anticancer and antifungus at the same time. The results showed that ph-ph+ could prevent the proliferation and metastasis of breast cancer cells, and kill C. albicans simultaneously. The molecular mechanism was associated with the activation of an evolutionarily conserved protease CLpP in the cancer and C. albicans cells. Also, the signaling pathway mediated by PLAGL2 that highly expressed in cancer cells participated in preventing cell metastasis and inducing apoptosis of ph-ph+. The one drug with dual targets inhibited the growth and metastasis of the cancer cells, and meanwhile eliminated C. albicans in tissues in the experimental animals. The results suggested that ph-ph+ with dual targets of CLpP and PLAGL2 would be a feasible approach to prolong the survival rate in patients with metastatic breast cancer and pathogenic infection.

Aims/Background Breast leukaemia (BL) is a rare breast malignancy that is treated differently from other malignant conditions. However, it is easily confused with other conditions; therefore, how to accurately diagnose is crucial. We retrospectively analysed the imaging findings of 13 patients to provide a diagnostic reference. Methods From January 2015 to April 2023, 13 patients with BL confirmed by biopsy who underwent imaging in Peking University People\'s hospital were retrospectively analysed. The imaging findings obtained via ultrasound (US), mammography (MMG), magnetic resonance imaging (MRI), and positron emission tomography/computed tomography (PET/CT) were analysed, and the detection rates of these methods for diagnosing BL were compared. Results Twenty-nine lesions were detected in the 13 patients. These patients presented with palpable masses or breast swelling several months after treatment for leukaemia, mainly involving the bilateral breasts. Ultrasonography was performed for 13 patients, and all lesions were detected. Most of the identified masses were hypoechoic and had indistinct boundaries, irregular shapes, no enhancement of the posterior echo, and no abundant blood flow. MMG was performed for five patients, revealing breast masses, architectural distortion, and no abnormalities. MRI was performed for four patients, and all lesions were detected; most of the lesions were hypointense on T1-weighted imaging and hyperintense on T2-weighted imaging and diffusion-weighted imaging, with a decreased apparent diffusion coefficient and inhomogeneous enhancement. The enhancement curves were mostly inflow patterns. PET/CT was performed for four patients; two patients had hypermetabolism, and the other two had no obvious radioactive uptake. Conclusion Compared to MMG and PET/CT, US and MRI have higher detection rates. Furthermore, compared to MRI, US is inexpensive, convenient and efficient; therefore, it should be the first choice for diagnosing BL.

OBJECTIVE: To assess T1 mapping performance in distinguishing between benign and malignant breast lesions and to explore its correlation with histopathologic features in breast cancer.
METHODS: This study prospectively enrolled 103 participants with a total of 108 lesions, including 25 benign and 83 malignant lesions. T1 mapping, diffusion-weighted imaging (DWI), and dynamic contrast-enhanced (DCE) were performed. Two radiologists independently outlined the ROIs and analyzed T1 and apparent diffusion coefficient (ADC) values for each lesion, assessing interobserver reliability with the intraclass correlation coefficient (ICC). T1 and ADC values were compared between benign and malignant lesions, across different histopathological characteristics (histological grades, estrogen, progesterone and HER2 receptors expression, Ki67, N status). Receiver operating characteristic (ROC) analysis and Pearson correlation coefficient (ρ) were performed.
RESULTS: T1 values showed statistically significant differences between benign and malignant groups (P < 0.001), with higher values in the malignant (1817.08 ms ± 126.64) compared to the benign group (1429.31 ms ± 167.66). In addition, T1 values significantly increased in the ER (-) group (P = 0.001). No significant differences were found in T1 values among HER2, Ki67, N status, and histological grades groups. Furthermore, T1 values exhibited a significant correlation (ρ) with ER (P < 0.01) and PR (P = 0.03). The AUC for T1 value in distinguishing benign from malignant lesions was 0.69 (95 % CI: 0.55 - 0.82, P = 0.005), and for evaluating ER status, it was 0.75 (95 % CI: 0.62 - 0.87, P = 0.002).
CONCLUSIONS: T1 mapping holds the potential as an imaging biomarker to assist in the discrimination of benign and malignant breast lesions and assessing the ER expression status in breast cancer.

To evaluate the effectiveness of the combination of acupoint embedding therapy and traditional Chinese medicine dialectical treatment regimen in improving clinical symptoms, promoting tumor regression, controlling adverse reactions and complications, and enhancing patient satisfaction by comparing and analyzing the clinical data of 120 breast tumor patients. One hundred twenty patients with breast cancer were divided into a treatment group (60 cases) and a control group (60 cases) according to different treatment plans. Patients in the treatment group received a combination of acupoint embedding therapy and traditional Chinese medicine dialectical treatment based on different time points of the menstrual cycle. Including the proportion of reduction in the number of breast masses, the proportion of reduction in mass size, changes in pain severity scores, tumor regression rate, regression time, incidence of adverse reactions and complications, and patient satisfaction. Statistical software was used to analyze the data to evaluate differences between the 2 groups. In terms of clinical symptoms, the proportion of reduction in the number of breast masses in the treatment group averaged 50%, significantly higher than the 25% in the control group; the proportion of reduction in mass size averaged 40%, also higher than the 15% in the control group; and the improvement in pain severity scores was also superior to the control group. Regarding tumor regression, the tumor regression rate in the treatment group reached 85%, with an average regression time of 6.2 weeks, both significantly better than the 55% and 9.8 weeks in the control group. In terms of adverse reactions and complications, the incidence rate in the treatment group was relatively low, and no serious adverse events occurred. Patient satisfaction surveys showed that the treatment group had significantly higher satisfaction with treatment effectiveness, treatment process, and physician service attitude compared to the control group. Based on clinical data from 120 breast tumor patients, the results of this study indicate that breast tumor patients treated with a specific treatment regimen have significant advantages in improving clinical symptoms, tumor regression, controlling adverse reactions and complications, and patient satisfaction. This treatment regimen has high clinical application value and deserves further promotion.

Several studies have confirmed the important role of endometrial cancer (EC) in the development and progression of breast cancer (BC), and this study will explore the causal relationship between EC and BC by 2-sample Mendelian randomization analysis. Pooled data from published genome-wide association studies were used to assess the association between EC and BC risk in women using 5 methods, namely, inverse variance weighting (IVW), MR-Egger, weighted median (WME), simple multimaximetry (SM) and weighted multimaximetry (WM) with the EC-associated genetic loci as the instrumental variables (IV) and sensitivity analyses were used to assess the robustness of the results. The statistical results showed a causal association between EC and BC (IVW: OR = 1.07, 95% CI = 1.01-1.32, P = .02; MR-Egger: OR = 1.21, 95% CI = 0.71-1.51, P = .11; weighted median: OR = 1.05, 95% CI = 0.97-1.31, P = .19; simple plurality method: OR = 0.98, 95% CI = 0.81-1.15, P = .78; weighted plurality method: OR = 0.98, 95% CI = 0.81-1.14, P = .75), and the results of the sensitivity analyses showed that there was no significant heterogeneity or multiplicity, and the results were stable. EC is associated with an increased risk of developing BC. The results of this MR analysis can be used as a guideline for screening for BC in women with EC and to help raise awareness of screening for early detection and treatment.

The effects and mechanisms of the Mediterranean diet (MD) on the incidence, recurrence, and prevention of breast cancer (BC) have been extensively investigated since the 1990s. Recent years have witnessed significant advancements in understanding the relationship between the components of the MD and BC, particularly in terms of their role and adherence. This comprehensive review focuses on several key aspects: the influence of the adherence of MD in cohort studies conducted across different regions on BC, the effects and mechanisms of individual component or main components as well as the supplementation of vitamins, drugs, exercise, and other factors of MD on BC; the variations in the impact of the MD on premenopausal and postmenopausal women, as well as different types in BC cases; the possible mechanisms underlying the development, recurrence, and prevention of BC in relation to the MD; and the interaction effects of individual genetic polymorphisms with the MD. Based on current research findings, this review highlights the key issues and identifies future research directions in investigating the relationship between the MD and BC. Furthermore, it suggests that healthy women of various ages and BC patients should adhere to MD in order to prevent BC or improve the prognosis.

BACKGROUND: Combining hydromorphone with ropivacaine in ultrasound-guided erector spinae plane blocks enhances postoperative analgesia and reduces interleukin-6 expression in breast surgery patients.
METHODS: In this study, breast cancer patients undergoing modified radical mastectomy were randomized into 3 groups for anesthesia (30 patients in each group): standard general (group C), Erector Spinae Plane Block (ESPB) with ropivacaine (group R), and ESPB with ropivacaine plus hydromorphone (group HR). Diagnosis: Breast cancer patients. Postsurgery, pain levels, IL-6, anesthetic doses, additional analgesia needs, and recovery milestones were compared to evaluate the efficacy of the ESPB enhancements.
RESULTS: The 3 groups were not significantly different in baseline characteristics, operation time, number of cases with postoperative nausea, and serum IL-6 concentrations at T1 (the time of being returned to the ward after surgery). At T2 (at 6:00 in the next morning after surgery), the serum IL-6 concentration in group HR was significantly lower than that in groups R and C (P < .05); the intraoperative doses of remifentanil, sufentanil, and propofol were significantly lower in groups HR and R than those in group C (P < .05); Groups HR and R had significantly lower visual analog scale scores at T3 (4 hours postoperatively), T4 (12 hours postoperatively), and T5 (24 hours postoperatively) than those in group C (P < .05); the proportions of patients receiving postoperative remedial analgesia were significantly lower in groups HR and R than in group C (P < .05); groups HR and R had significantly lower proportions of patients with postoperative nausea than group C (P < .05); the time to the first anal exhaust and the time to the first ambulation after surgery were significantly shorter in groups HR and R than those in group C (P < .05).
CONCLUSIONS: Hydromorphone combined with ropivacaine for ESPB achieved a greater postoperative analgesic effect for patients receiving MRM under general anesthesia. The combined analgesia caused fewer adverse reactions and inhibited the expression level of the inflammatory factor IL-6 more effectively, thereby facilitating postoperative recovery. ESPB using hydromorphone with ropivacaine improved pain control post-MRM, reduced adverse effects, and more effectively suppressed IL-6, enhancing recovery.

Angiogenesis is considered a hallmark pathophysiological process in tumor development. Aberrant vasculature resulting from tumor angiogenesis plays a critical role in the development of resistance to breast cancer treatments, via exacerbation of tumor hypoxia, decreased effective drug concentrations within tumors, and immune-related mechanisms. Antiangiogenic therapy can counteract these breast cancer resistance factors by promoting tumor vascular normalization. The combination of antiangiogenic therapy with chemotherapy, targeted therapy, or immunotherapy has emerged as a promising approach for overcoming drug resistance in breast cancer. This review examines the mechanisms associated with angiogenesis and the interactions among tumor angiogenesis, the hypoxic tumor microenvironment, drug distribution, and immune mechanisms in breast cancer. Furthermore, this review provides a comprehensive summary of specific antiangiogenic drugs, and relevant studies assessing the reversal of drug resistance in breast cancer. The potential mechanisms underlying these interventions are discussed, and prospects for the clinical application of antiangiogenic therapy to overcome breast cancer treatment resistance are highlighted.

Breast cancer (BC) is the most common malignancy in women worldwide. Wnt signaling is involved in tumorigenesis and cancer progression, and is closely associated with the characteristics of BC. Variation in the expression of exosomal microRNAs (miRNAs) modulates key cancer phenotypes, such as cellular proliferation, epithelial‑mesenchymal transition, metastatic potential, immune evasion and treatment resistance. The present review aimed to discuss the importance of Wnt signaling and exosomal miRNAs in regulating the occurrence and development of BC. In addition, the present review determined the crosstalk between Wnt signaling and exosomal miRNAs, and highlighted potential diagnostic biomarkers and therapeutic targets.