Purpose: Many breast cancer patients experience genitourinary syndrome of menopause (GSM) symptoms. Concerns about systemic absorption limit the use of local estrogen therapy, and clinicians are often hesitant to prescribe it to breast cancer survivors.Therefore, other treatment options are essential. The aim of this study was to examine the safety and effectiveness of fractional CO2 laser treatment in breast cancer survivors experiencing GSM. Materials and Methods: Each woman received three fractional CO2 treatments at 4-week intervals between sessions: baseline (V1), 4-week follow-up (V2), 8-week follow-up (V3), and a final follow-up at 12 weeks (V4). Breast cancer survivors who had one or more symptoms related to GSM qualified for inclusion in this study. Severity of symptoms was assessed with a visual analog scale (VAS) at baseline and every follow-up visit. We also measured GSM objectively using the vaginal health index score (VHIS) at every visit. At V4, patients evaluated their satisfaction with laser therapy using a 5-point Likert scale. Results: Twenty-four women were included in the study. Almost all symptoms showed improvement based on mean VAS score after treatment. Vaginal dryness and urgency improved after the second treatment. After completion of all treatments, all symptoms except frequency showed improvement. VHIS increased significantly after completion of laser treatment (8.5±3.1 at baseline vs. 16.2±2.9 at V4; p<0.001). Conclusion Fractional CO2 laser treatment appears to be an effective and safe method in breast cancer survivors with GSM.

This study aimed to determine the prevalence of human epidermal growth factor receptor 2 (HER2)–ultralow breast cancer among cases initially classified as HER2 immunohistochemistry (IHC) 0 and assess interobserver variability in interpreting low-level HER2 expression. Methods: In this multicenter retrospective study, all invasive breast cancer cases diagnosed between January and December 2022 across 10 Korean institutions were retrieved. Institutional pathologists reexamined HER2 IHC slides originally reported as IHC 0 according to the 2018 American Society of Clinical Oncology/College of American Pathologists guidelines and reclassified them as HER2-null (0), HER2-ultralow (0+), or HER2-low (1+). Slides from 10% of HER2-null and HER2-ultralow cases were digitized for central review and independently assessed by two pathologists, with discrepancies resolved by consensus. Results: Among 8,026 cases, 2,836 cases (35.5%) were initially reported as IHC 0. Upon re-review, 1,673 (59.0%), 1,139 (40.2%), and 24 (0.8%) cases were reclassified as HER2-null, HER2-ultralow, and HER2-low, respectively. The prevalence of HER2-ultralow breast cancer varied considerably across institutions (23.7%–78.1%). Central review of 268 digitized cases showed concordance in 193 cases (72.0%). Among the 75 discordant cases, 54 tumors (72.0%) were upgraded from HER2-null to HER2-ultralow, and 18 (24.0%) tumors were upgraded from HER2-ultralow to HER2-low. Furthermore, two tumors (2.7%) were downgraded from HER2-ultralow to HER2-null. Conclusions: Approximately 40% of cases initially categorized as IHC 0 were reclassified as HER2-ultralow. The substantial inter-institutional variability observed in interpreting low-level HER2 expression highlights the need for standardized training and quality assurance to ensure accurate identification of patients eligible for HER2-targeted antibody–drug conjugates.

Purpose: While TP53 mutations are well known to be associated with adverse prognosis in hematological diseases, their functional impact remains incompletely understood. This study examines the spectrum of TP53 mutations across various hematologic malignancies and evaluates their functional impact. Materials and Methods: Using targeted sequencing panels, we analyzed TP53 mutations in the bone marrow aspiration samples of a retrospective cohort of 856 patients diagnosed with hematologic malignancies. To assess the impact of TP53 mutations, we applied the evolutionary action (EAp53) score and the relative fitness score (RFS), previously proposed functional scoring methods. The effects of variant allele frequency (VAF), disruptive mutations, EAp53 score, and RFS on overall survival (OS) were evaluated. Results: TP53 mutations were associated with inferior OS compared with wildtype TP53 (median OS 10.0 months versus not estimable; hazard ratio (HR) 4.6; p<0.001). In the acute myeloid leukemia, multiple myeloma, and myelodysplastic syndrome subgroups, TP53 mutations had a significant adverse impact on OS. (HRs 3.8, 4.2, 6.0, respectively; p<0.001, p=0.005, p<0.001, respectively). Patients with VAF >50% had significantly poorer OS compared to those with VAF ≤50% (median OS 7.5 months versus 22.8 months; HR 2.2, p=0.016). Moreover, patients in the high-risk RFS group (RFS >0.22) had significantly worse OS compared to those in the low-risk RFS group (RFS ≤0.22) (median OS 5.6 months versus 16.3 months; HR 2.2, p=0.041). However, no significant survival difference was observed between the EAp53 high-risk (>75) and low-risk (≤75) groups, or between patients with disruptive and non-disruptive mutations. Conclusion Our findings highlight VAF and RFS as valuable tools for stratifying TP53-mutant patients into high-risk and low-risk groups.

Purpose: Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer, with approximately 30% of patients eventually developing brain metastases (BM), which result in poor outcomes. An understanding of the tumor microenvironment (TME) at both primary and metastatic sites offers insights into the mechanisms underlying BM and potential therapeutic targets. Materials and Methods: Spatial RNA sequencing (spRNA-seq) was performed on primary TNBC and paired BM tissues from three patients, one of whom had previously received immune checkpoint inhibitors before BM diagnosis. Specimen regions were categorized into tumor, proximal, and distal TME based on their spatial locations. Gene expression differences across these zones were analyzed, and immune cell infiltration was estimated using TIMER. A gene module analysis was conducted to identify key gene clusters associated with BM. Results: Distinct gene expression profiles were noted in the proximal and distal TMEs. In BM, the proximal TME exhibited neuronal gene expression, suggesting neuron-tumor interactions compared to tumor, and upregulation of epithelial genes compared to the distal TME. Immune cell analysis revealed dynamic changes in CD8+ T cells and macrophages across the tumor and TME zones. Gene module analysis identified five key modules, including one related to glycolysis, which correlated with patient survival. Drug repurposing analysis identified potential therapeutic targets, including VEGFA, RAC1, EGLN3, and CAMK1D. Conclusion This study provides novel insights into the transcriptional landscapes in TNBC BM using spRNA-seq, emphasizing the role of neuron-tumor interactions and immune dynamics. These findings suggest new therapeutic strategies and underscore the importance of further research.

Background: With the introduction of disease-modifying treatments for Alzheimer’s disease (AD), less invasive and widely accessible screening tests are urgently needed. We assessed eight blood-based biomarkers in a well-defined cohort of preclinical AD, including participants with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). Methods: Amyloid beta (Aβ) oligomerization tendency, Aβ42, Aβ40, Aβ42/Aβ40 ratio, phosphorylated tau (p-tau)181, p-tau217, glial fibrillary acidic protein (GFAP), and neurofilament light (Nf-L) were assessed for distinguishing between SCD and MCI, for correlations, and for predicting Aβ positron emission tomography (PET) positivity. Results: Plasma p-tau181, p-tau217, and GFAP levels were significantly higher in participants with MCI than in those with SCD (P < 0.05) and in Aβ PET-positive versus Aβ PET-negative participants (P < 0.0001), whereas plasma Aβ42 and Aβ42/40 ratio levels were significantly lower in Aβ PET-positive than in Aβ PET-negative participants (P < 0.001). Logistic regression analysis revealed that plasma Aβ42 and p-tau217 levels predicted Aβ PET positivity with an area under the ROC curve (AUC) of 0.930 (95% confidence interval [CI], 0.848–0.976) in the entire cohort, and p-tau217 alone predicted Aβ PET-positivity with an AUC of 0.887 (95% CI, 0.779–0.954) in the MCI subgroup. Conclusions Plasma p-tau217 levels outperform plasma p-tau181 levels in predicting Aβ PET-positivity in participants with preclinical AD. Plasma GFAP levels, along with different ptau isoforms (p-tau181 and p-tau217), effectively differentiate MCI from SCD. The predictive accuracy of blood-based biomarkers for Aβ PET-positivity strongly supports their clinical implementation, particularly with the introduction of disease-modifying therapies.

Background: TP53 mutations are associated with poor prognosis in myelodysplastic neoplasm (MDS) and AML. The updated 5th WHO classification and International Consensus Classification (ICC) categorize TP53-mutated MDS and AML as unique entities. We conducted a multicenter study in Korea to investigate the characteristics of TP53-mutated MDS and AML, focusing on diagnostic aspects based on updated classifications. Methods: This study included patients aged ≥ 18 yrs who were diagnosed as having MDS(N = 1,244) or AML (N = 2,115) at six institutions. The results of bone marrow examination, cytogenetic studies, and targeted next-generation sequencing, including TP53, were collected and analyzed. Results: TP53 mutations were detected in 9.3% and 9.2% of patients with MDS and AML, respectively. Missense mutation was the most common, with hotspot codons R248/ R273/G245/Y220/R175/C238 accounting for 25.4% of TP53 mutations. Ten percent of patients had multiple TP53 mutations, and 78.4% had a complex karyotype. The median variant allele frequency (VAF) of TP53 mutations was 41.5%, with a notable difference according to the presence of a complex karyotype. According to the 5th WHO classification and ICC, the multi-hit TP53 mutation criteria were met in 58.6% and 75% of MDS patients, respectively, and the primary determinants were a TP53 VAF > 50% for the 5th WHO classification and the presence of a complex karyotype for the ICC. Conclusions Collectively, we elucidated the molecular genetic characteristics of patients with TP53-mutated MDS and AML, highlighting key factors in applying TP53 mutation-related criteria in updated classifications, which will aid in establishing diagnostic strategies.

Endometriosis, a prevalent but debilitating condition affecting women, poses significant challenges in diagnosis and management. The current 2024 guideline, developed by the Korean Society of Endometriosis (KSE), builds upon the 2018 KSE guideline. This guideline aims to provide customized recommendations tailored to Korea’s unique clinical aspects and medical environment, and addresses key areas such as diagnosis, medical and surgical management, considerations for special populations, and its complex relationship with cancer.

Background: Histone deacetylase (HDAC) inhibition offers potential anticancer effects across diverse cancers due to HDAC's significant role in cancer development and progression. Consequently, we demonstrated the therapeutic efficacy of the novel HDAC inhibitor, CG-745, in comparison with existing inhibitors such as suberoylanilide hydroxamic acid (SAHA) in non-small cell lung cancer (NSCLC) cells. Methods: CG-745's effect on apoptosis and reactive oxygen species (ROS)-dependent mitochondrial dysfunction was investigated using annexin V assay, MitoSoX, and Western blot in human A549 and H460 cells. Additionally, HDAC expression was analyzed through real-time polymerase chain reaction. We also evaluated the inhibitory effect of CG-745 on epithelial-mesenchymal transition (EMT) induced by transforming growth factor β1 (TGF-β1) via Western blot, scratch analysis, and matrigel invasion analysis. Results: Compared to SAHA, CG-745 inhibited cell viability and mRNA expression of HDACs such as HDAC1, HDAC2, HDAC3, and HDAC8. It also induced apoptosis, ROS, and mitochondrial dysfunction in a concentration-dependent manner. CG-745 reversed EMT triggered by TGF-β1 in A549 and H460 cells, and curtailed the migration and invasion enhanced by TGF-β1. CG-745 has demonstrably inhibited EMT and induced apoptosis in NSCLC cells. Conclusion CG-745 may represent a novel therapeutic strategy for NSCLC treatment.

Endometriosis, a prevalent but debilitating condition affecting women, poses significant challenges in diagnosis and management. The current 2024 guideline, developed by the Korean Society of Endometriosis (KSE), builds upon the 2018 KSE guideline. This guideline aims to provide customized recommendations tailored to Korea’s unique clinical aspects and medical environment, and addresses key areas such as diagnosis, medical and surgical management, considerations for special populations, and its complex relationship with cancer.

We evaluated the effectiveness of the predictive low-glucose suspend (PLGS) algorithm in the DIA:CONN G8. Forty people with type 1 diabetes mellitus (T1DM) who used a DIA:CONN G8 for at least 2 months with prior experience using pumps without and with PLGS were retrospectively analyzed. The objective was to assess the changes in time spent in hypoglycemia (percent of time below range [%TBR]) before and after using PLGS. The mean age, sensor glucose levels, glucose threshold for suspension, and suspension time were 31.1±22.8 years, 159.7±23.2 mg/dL, 81.1±9.1 mg/dL, and 111.9±79.8 min/day, respectively. Overnight %TBR <70 mg/dL was significantly reduced after using the algorithm (differences=0.3%, from 1.4%±1.5% to 1.1%±1.2%, P=0.045). The glycemia risk index (GRI) improved significantly by 4.2 (from 38.8±20.9 to 34.6±19.0, P=0.002). Using the PLGS did not result in a change in the hyperglycemia metric (all P>0.05). Our findings support the PLGS in DIA:CONN G8 as an effective algorithm to improve night-time hypoglycemia and GRI in people with T1DM.