BACKGROUND:Breast density is both an independent risk factor for breast cancer and a major determinant of mammographic diagnostic performance. However, its impact on overall screening performance within population-based screening programs is less well understood. METHODS:This retrospective cohort study included women aged 50-74 years screened through BreastScreen NSW between 1 January 2016 and 31 December 2017, excluding first-time screeners above 70. Breast density was assessed using Lunit INSIGHT MMG (v1.1.7) generating an ordinal density score (1-10) and corresponding BI-RADS category (A-D). Screen-detected and interval cancers were ascertained via the NSW BreastScreen Information System and the NSW Cancer Registry. Standard screening performance metrics were calculated stratified by age, breast density and screening round. RESULTS:The cohort comprised 564,681 screening episodes, with 4758 cancers diagnosed (3756 screen-detected; 1002 interval). Cancer incidence rates and screening performance varied by breast density. The proportion of cancers that were interval cancers increased markedly with increasing density, from 10.9% of cancers in category A (least dense) to 46.6% in category D. Recall rates followed an N-shaped pattern, peaking in density category C, while specificity mirrored this relationship. CONCLUSION:The effectiveness of conventional two-dimensional mammography is strongly dependent on breast density, with reduced sensitivity and increased interval cancer rates for clients with extremely dense breasts. By utilising a more granular measure of breast density in a large population screening cohort, this study identified nonlinear relationships between breast density and screening performance metrics, providing evidence to support future evaluation of more individualised screening approaches.
BACKGROUND:Breast cancer comprehensive therapies often cause body image changes, triggering stigma that impairs mental health and quality of life. Existing studies lack an integrated model to reveal the underlying mechanisms between these variables. METHODS:A cross-sectional survey was conducted among 292 breast cancer patients selected via convenience sampling from 5 hospitals in Guangdong Province between March 2021 and March 2022. The Distress Disclosure Index (DDI), Consumer Experiences of Shame Questionnaire (CESQ), Functional Assessment of Cancer Therapy-Breast (FACT-B), and Multidimensional Scale of Perceived Social Support (PSSS) scales were administered. Pearson correlation analysis explored variable relationships, structural equation modeling (SEM) constructed the chain mediating model, the Bootstrap method tested mediating effects, and subgroup associations with stigma were analyzed. RESULTS:Breast cancer patients had self-disclosure and stigma scores of 38.17 ± 0.54 and 13.74 ± 0.42, respectively. Stigma was significantly negatively correlated with self-disclosure, social support, and quality of life (all p < 0.01). Self-disclosure was directly associated with lower stigma (β = -0.52, p < 0.001) and indirectly mediated by two pathways: the independent pathway through "better quality of life" (11.6% of total effect) and the chain pathway through "higher social support and better quality of life" (5.4% of total effect). Subgroup analysis indicated that patients with a bachelor's degree or above were more significantly associated with low stigma (OR = 0.42, 95% CI: 0.17-0.96), while introverted patients showed a stronger association with high stigma than extroverted ones (OR = 2.90, 95% CI: 1.57-5.56). CONCLUSION:Breast cancer patients exhibit relatively low self-disclosure and moderate-to-low stigma. Higher self-disclosure is associated with lower stigma directly or indirectly via the chain mediation of social support and quality of life. Enhancing psychological counseling, social support, and quality of life, paired with targeted interventions for education and personality subgroups, facilitates physical and mental recovery and social reintegration.
OBJECTIVE:To develop and validate an interpretable machine learning (ML) model for predicting malignant risk in patients with breast nodules using serum lipid biomarkers. METHODS:This retrospective study included 899 patients with breast nodules (236 malignant) admitted between March 2022 and December 2024. Patients were randomly assigned to a training cohort (n = 630) and an internal validation cohort (n = 269) at a 7:3 ratio. Baseline clinical and laboratory data were collected upon admission. Following feature selection via LASSO regression, the predictive performance of 8 ML algorithms was evaluated and compared using receiver operating characteristic (ROC) curves. The optimal model's performance was further corroborated using an independent temporal validation cohort of 190 patients (admitted Jan-Aug 2025). Model interpretability was addressed using SHapley Additive exPlanations (SHAP). RESULTS:Nine key predictors were identified from 20 candidates by Lasso regression and clinical expertise. The random forest (RF) model outperformed other algorithms, achieving areas under the curve (AUC) values of 0.789, 0.782, and 0.825 for the training, internal validation, and temporal validation cohorts, respectively. Hosmer-Lemeshow tests (p > 0.05) indicated high calibration between the predicted and observed risks. SHAP importance analysis revealed Fer, age, and CEA to be the top three predictive factors. CONCLUSION:The RF model based on serum lipid biomarkers serves as a robust, noninvasive tool for assessing breast cancer risk, showing significant potential for clinical decision support in screening programs.
BACKGROUND AND AIMS:Breast cancer is the most abundant cancer type in female. Genome-wide association study suggests that rs2016394, one SNP at the intron of DLX2 divergent transcript (DLX2-DT), is significantly associated with this disease. Through 1000 genomes project data analysis, it is observed that another three SNPs, rs743605, rs2357322, and rs17726078, show strong linkage disequilibrium with rs2016394. However, the functional SNP(s) and mechanism are still unknown. METHODS:Functional genomics effort was performed for this locus. RESULTS:Through luciferase assay, it is disclosed that rs743605 and rs2016394 are not with the ability to alter gene expression. In contrast, rs2357322 and rs17726078 alleles present significantly different luciferase expression, thus suggesting that these two SNPs are functional mutations. Chromosome conformation capture indicates that DLX2 (distal-less Homeobox 2) can interact with the cis-regulatory element containing these two SNPs and should be the regulatory target. Chromatin immunoprecipitation suggests that transcription factor MYC (MYC proto-oncogene, bHLH transcription factor) can bind the rs17726078 surrounding region. Knock-out of the segment containing these two SNPs by CRISPR/Cas9 can significantly increase DLX2 mRNA and protein expression, cell proliferation, colony formation, migration, and wound healing, thus suggesting that the cis-regulatory element is an attenuator for gene expression. CONCLUSION:rs2357322 and rs17726078 might influence DLX2 expression and further contribute to breast cancer risk.
BACKGROUND:Breast cancer is a leading female malignancy, with chronic inflammation driving progression. The IL-2/IL-2R axis regulates immunity, but IL2RA's role in breast cancer (expression, diagnostic/prognostic value, and interplay with IL-2) is unclear. METHODS:A total of 252 consecutive patients (99 breast cancer and 153 benign breast disease) who received breast surgery were retrospectively analyzed. Serum cytokines were measured via electrochemiluminescence immunoassay; ROC, single-cell sequencing, and bioinformatics databases (TIMER and Kaplan-Meier plotter) were used to assess IL2RA/IL-2's utility and associations. RESULTS:Serum IL2Rα was higher in breast cancer (336.9 vs. 275.8 U/mL, p < 0.001; no significant differences were observed for other cytokines). IL2Rα showed moderate diagnostic performance (AUC = 0.650, cut-off = 240.5 U/mL), correlated with NLR (p = 0.012), and showed a trend towards poor survival (p = 0.124, HR = 0.309, 95% CI: 0.069-1.381). Single-cell sequencing identified T cells as the primary source of IL2Rα in tumor tissues. High IL2RA expression strongly correlated with infiltration of immune cells, especially neutrophils (r = 0.673) and dendritic cells (r = 0.706). RNA-seq analysis showed IL2RA was upregulated in tumor tissues, associated with poor prognosis (p = 9.7e - 06, HR = 1.29, 95% CI: 1.15-1.44) and aggressive features (e.g., lymph node metastasis and HER2 positivity). In contrast, IL-2 was highly expressed in normal tissues, linked to better prognosis (p = 0.001, HR = 0.83, 95% CI: 0.74-0.93), and had opposing clinical correlations. CONCLUSIONS:Serum IL2Rɑ could serve as a complementary auxiliary diagnostic biomarker for breast cancer, with associations with systemic inflammation, immune cell infiltration, and aggressive disease. The functional antagonism between IL2RA and IL-2 highlights the IL-2/IL2RA axis as a critical regulator of breast cancer pathophysiology, supporting its potential as a therapeutic target for improving breast cancer diagnosis and treatment.
BACKGROUND:Although increasing research has shown that extremely low-frequency electromagnetic fields (ELF-EMFs) specifically trigger PCD through the elevation of ROS levels in cancer cells, there is no adequate evidence to determine the exact mechanisms of this phenomenon. The antioxidant machinery may play a crucial role in this area; however, this has been neglected in previous research. METHODS:The main aim of this study was to assess the effect of ELF-EMF exposure (5 days, 1 Hz, 100 mT, 2 h/day) on ROS levels, expression levels of antioxidant genes, and apoptosis induction in different breast cancer molecular subtypes with different p53 statuses. RESULTS:DCFH-DA results revealed that the ROS level increased in all three cell lines (SKBR-3, MDA-MB-231, and MCF-7); this increase was much greater in SKBR-3 (up to 5-fold compared to its sham exposure). This result was concurrent with the annexin V/PI results; SKBR-3 cells showed much more apoptosis induction (about 78%), compared with the others (22% or 11% in the other two cells). On the other hand, the mRNA expression level of SOD1 and SOD2 increased significantly in the MDA-MB-231, in addition to these two genes, the expression level of SOD3 and GSR increased in the MCF-7 cells but not in the SKBR-3. CONCLUSION:Taken together, our results confirmed that ELF-EMF induced ROS-dependent apoptosis, especially in HER-2-enriched breast cancer cells (the SKBR-3), in a p53-independent manner. Other molecular subtypes (MDA-MB-231 as TNBC, or MCF-7 as luminal A) showed resistance against the ROS level increasing and subsequent apoptosis induction by using antioxidant genes, especially SOD1.
BACKGROUND:Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis. Neoadjuvant immunochemotherapy (NAIC) combining chemotherapy and pembrolizumab is now standard for Stage II-III TNBC. This study evaluates the impact of NAIC on surgical outcomes versus neoadjuvant chemotherapy (NAC). METHODS:A retrospective cohort study included 117 Stage II-III TNBC patients treated with NAIC or NAC (October 2019-May 2023). Surgical complications, time to surgery, time to radiotherapy, and pathologic response were assessed. Complications were classified using the Clavien-Dindo scale; immune-related adverse events (irAEs) followed the 2017 CTCAE criteria. RESULTS:Among 117 patients, 59 received NAIC and 58 NAC. Chemotherapy-related adverse events were similar (NAIC: 78.0%, NAC: 75.9%). irAEs occurred in 50.8% of NAIC patients, with 8.5% experiencing severe irAEs. Surgical complications were more frequent in NAIC (27.1%) than NAC (17.2%), though not statistically significant; seroma was the most common. Delays > 12 weeks in initiating radiotherapy were more frequent in NAIC (10.7%) than NAC (0%). CONCLUSION:NAIC did not significantly increase postoperative complications compared to NAC. However, irAEs and potential treatment delays warrant careful management. Despite these risks, NAIC remains a viable option for early TNBC with manageable surgical outcomes.
BACKGROUND:Selenium (Se) and zinc (Zn) are essential micronutrients that play roles in antioxidant defense and the regulation of cell proliferation. Increasing evidence suggests that disturbances in trace element balance may contribute to breast carcinogenesis; however, findings across studies remain inconsistent. OBJECTIVE:To evaluate the association between circulating and tissue Se and Zn levels and breast cancer. METHODS:A systematic review and meta-analysis were conducted according to PRISMA 2020 and MOOSE recommendations. Searches were performed in MedLine, EMBASE, and LILACS from database inception until April 15, 2026. Case-control studies comparing selenium and zinc levels between women with breast cancer and control groups were eligible. Two independent reviewers performed study selection, data extraction, risk-of-bias assessment, and publication bias analysis using Egger's regression test. RESULTS:Thirty case-control studies were included. Most studies (83.3%) were classified as high methodological quality according to the Newcastle-Ottawa Scale. Meta-analyses revealed significantly lower selenium levels in plasma (MD = -12.10 μg/L; 95% CI: -17.54 to -6.65; p < 0.0001), selenium in nails (MD = -0.02 μg/g; 95% CI: -0.04 to -0.01; p = 0.006), and zinc in plasma (MD = -0.33; 95% CI: -0.47 to -0.19; p < 0.00001) in breast cancer patients compared with controls. CONCLUSIONS:The pooled findings indicate an inverse association between breast cancer and selenium levels measured in plasma and nails, as well as plasma zinc concentrations. Nevertheless, interpretation should remain cautious because all included studies had observational designs, with marked heterogeneity and potential residual confounding. Lower circulating selenium and zinc levels, together with reduced selenium concentrations in nails, were associated with breast cancer occurrence. Additional prospective studies are required to clarify causality and determine the clinical significance of these associations.
INTRO:Divergence from national guidelines and variations in practice patterns impact care and outcomes in patients with metastatic breast cancer (MBC). We sought to assess the quality of care in the diagnosis and treatment of real-world patients with MBC in Washington State. METHODS:Data were retrospectively analyzed using a linked cancer registry and insurance claims platform for patients with recurrent or de novo MBC diagnosed between 2008 and 2019. RESULTS:We identified 1101 patients with MBC (median age: 66), 715 recurrent and 386 de novo. Most patients were White (89%), all were insured (Commercial [47%], Medicaid [4%], Medicare [35%], or multiple [13%]), and 15% lived in areas of high deprivation (Area Deprivation Index [ADI]: 8-10). Of the patients with recurrent MBC, less than half received a biopsy (49.5%) or biomarker reassessment (48.7%) to confirm the diagnosis of MBC. Patients treated at high- and medium-volume centers had higher rates of biopsy than low-volume clinics (51.9%, 54.3%, and 40.7%, respectively, p = 0.03). ET alone was more common in patients who did not undergo biopsy (62.3% vs. 37.7%, p < 0.001) or biomarker reassessment (62.7% vs. 37.3%, p < 0.001). Among the 677 patients with estrogen receptor (ER)+/HER2- MBC (de novo and recurrent), most received ET alone (69%), followed by CT (22%) and CDKi + ET (9%). Importantly, 40% of patients were treated before CDK4/6i approval. Most patients who received CDKi + ET were < 65 years old (65.2%, p < 0.02). Patients with commercial insurance were more likely to receive CDKi + ET compared to those with Medicare/Medicaid. (60.9% vs. 26.1%, p = 0.10). CONCLUSION:Our findings highlight key gaps in MBC management and serve as a launch point for patient-centered and quality-promoting initiatives.
BACKGROUND:Accurate preoperative tumor size measurement is essential for determining optimal surgical margins in breast cancer patients. Thus, this study aimed to evaluate the factors associated with preoperative radiological tumor underestimation in clinical T (cT) Stage 1-2 breast cancer patients. METHODS:We retrospectively reviewed the data of 365 cT1-2 breast cancer patients. Radiological tumor size was defined as the larger dimension on ultrasonography or magnetic resonance imaging. A pathological-to-radiological tumor size ratio > 1.2 or a tumor size discrepancy (pathology minus radiology) ≥ 5 mm was considered indicative of radiological underestimation. Preoperative variables, including age, body mass index (BMI), cT stage, maximum standardized uptake value of tumor, molecular subtype, and histologic subtype and grade, were analyzed to identify associated factors. Tumor size discrepancy (pathology minus radiology) was compared across subgroups, and the difference between pathological and radiological tumor size measurements was evaluated in each subgroup. RESULTS:A BMI ≥ 25 kg/m2 (p = 0.006) and invasive lobular carcinoma (ILC) histology (p = 0.030) were associated with a pathological-to-radiological tumor size ratio > 1.2. A BMI ≥ 25 kg/m2 (p = 0.015), ILC histology (p = 0.022), and cT stage (p = 0.027) were associated with a tumor size discrepancy (pathology minus radiology) ≥ 5 mm. Significant differences in tumor size discrepancy between patients with a BMI ≥ 25 kg/m2 and those with a BMI < 25 kg/m2 (p = 0.003) and between patients with an ILC and those with non-ILC (p = 0.041) were observed. Bland-Altman analysis showed radiological underestimation in ILCs (4.3 mm). CONCLUSION:In cT1-2 breast cancer patients, a BMI ≥ 25 kg/m2 and/or an ILC are predictive of radiological tumor underestimation, warranting supplemental imaging and intraoperative margin assessment.
BACKGROUND:Breast cancer treatments, including chemotherapy, radiotherapy, endocrine therapy, targeted therapy, and surgical interventions, have significantly improved survival rates. However, these treatments are associated with long-term side effects that can impact the quality of life of survivors. Understanding these adverse effects is crucial for optimizing survivorship care. METHODS:This systematic review was conducted following PRISMA guidelines to assess the long-term side effects of breast cancer treatments. A comprehensive literature search was performed for studies published between 2005 and 2024. Studies examining long-term (≥ 12 months posttreatment) adverse effects in breast cancer survivors were included, with data extraction and risk of bias assessments conducted by independent reviewers. RESULTS:The review identified a broad spectrum of long-term side effects, including cardiovascular complications, cognitive impairment, persistent fatigue, lymphedema, menopausal symptoms, and psychological distress. Chemotherapy was frequently associated with peripheral neuropathy and cognitive decline, while radiotherapy increased the risk of fibrosis, secondary malignancies, and ischemic heart disease. Endocrine therapy contributed to osteoporosis, joint pain, and metabolic disturbances, whereas HER2-targeted therapies were linked to cardiotoxicity. In addition, surgical interventions, particularly axillary lymph node dissection, were a primary cause of lymphedema. Psychological distress, including anxiety, depression, and posttraumatic stress disorder, was also prevalent among survivors. CONCLUSION:The long-term side effects of breast cancer treatments highlight the need for comprehensive survivorship care, including routine monitoring, personalized rehabilitation programs, lifestyle modifications, and psychosocial support. Future research should focus on identifying risk factors, developing targeted interventions, and optimizing treatment strategies to minimize adverse effects and improve the quality of life for breast cancer survivors.
BACKGROUND:Hyperplasia of mammary glands (HMG) is a common benign disease of the female breast. OBJECTIVE:This study aimed to observe the clinical efficacy and safety of Honghua Xiaoyao pills in the treatment of liver depression and haemostasis-type HMG, as well as their impact on menstruation. METHODS:Sixty patients diagnosed with liver depression and haemostasis-type HMG in the breast disease department of our hospital were selected as the study participants. The treatment involved oral administration of Honghua Xiaoyao pills: four pills per dose, three times a day, for a duration of 3 months without interruption during menstruation. Hormones, Western painkillers and similar Chinese herbal medicines were prohibited during the trial. Changes in breast pain, breast masses, menstrual volume and safety indicators were observed. RESULTS:Three patients were lost to follow-up after 2 months of treatment, and four patients voluntarily withdrew from the study. The changes in breast pain scores, breast mass size scores and breast mass texture scores relative to baseline and their respective change rates showed statistically significant differences (p < 0.0001). Changes in lower abdominal distension, breast distension, menstrual blood clots, chest tightness/discomfort and emotional scores relative to baseline were also statistically significant (p < 0.0001). CONCLUSION:Honghua Xiaoyao pills are effective in reducing breast pain, shrinking breast masses and improving lower abdominal distension, breast distension, menstrual blood clots, chest tightness/discomfort and emotional symptoms in patients with liver depression and haemostasis-type HMG. TRIAL REGISTRATION:International Traditional Medicine Clinical Trial Registry: ITMCTR2024000165.
Historically, HER2 status in invasive breast cancer has been categorized as HER2-positive (IHC 3+, IHC 2+/ISH+) or HER2-negative (IHC 0, IHC 1+, IHC 2+/ISH-). Patients meeting IHC 0 with membrane staining (HER2-ultralow) criteria may benefit from HER2-targeted therapies such as trastuzumab deruxtecan. This cohort study assessed the prevalence of HER2-ultralow expression by re-scoring HER2 IHC slides using Mayo Clinic electronic health record data. Three hundred patients with advanced breast cancer (Stages III-IV) and documented HER2 IHC 0 status (January 2017-March 2023) were identified. One slide per patient was digitized and independently re-scored by two Mayo Clinic pathologists following the 2023 ASCO-CAP guidelines, including tumor staining percentage to denote HER2-ultralow status. A sensitivity analysis was performed by a third independent pathologist. The re-scored patients had a mean age of 57.7 years (SD = 13.6). Most samples (95%, n = 285) remained scored IHC 0 by at least one pathologist; 60% of these met HER2-ultralow criteria per at least one pathologist. HER2-ultralow prevalence ranged from 43% to 45% per pathologist, with 57% overall interpathologist concordance. Samples with no observable staining comprised most of the concordant cases. Treatment patterns were similar between HER2-ultralow and no-staining groups; however, time to treatment failure (TTF) varied between groups across lines of therapy (LOT). In HR- positive cohorts, median TTF for LOT1 was 7.73 months in patients with HER2-ultralow versus 9.43 months with no observable IHC staining. In HR- negative cohorts, median TTF was 5.00 months for HER2-ultralow versus 3.17 months with no observable IHC staining. Similar TTF trends were observed in LOT2-LOT3. Approximately three in five samples originally classified as IHC 0 met HER2-ultralow criteria, suggesting many patients may benefit from HER2-directed therapy if reclassified. These findings highlight potential challenges of identifying HER2-ultralow expression and suggest the need for enhanced pathologist training, adherence to best practices, and integration of digital pathology and artificial intelligence solutions. Trial Registration: ClinicalTrials.gov_identifier: NCT03734029.
BACKGROUND:Liver metastasis is a key adverse prognostic factor in breast cancer patients. This research was aimed to assess the development, risk factors, and prognostic determinants of breast cancer liver metastasis (BCLM). METHODS:We retrospectively analyzed the data of breast cancer from the Surveillance, Epidemiology, and End Results (SEER) (N = 560,908) and Jiangsu Province Hospital (JSPH) database (N = 294). The risk factors for BCLM were identified via multivariate logistic regression, and overall survival (OS) was assessed with Kaplan-Meier (KM) survival curves and Cox regression models. RESULTS:In the SEER cohort, liver metastasis attacked 1.3% of patients, and the highest incidence was found in the HR-/HER2+ subtype (4.4%). The risk factors for BCLM include young age, high pathological grade, concurrent bone, lung or brain metastasis, and HER2-positive or triple-negative subtype. The median OS of BCLM patients was short (SEER: 22 months; JSPH: 33.5 months). OS was shorter in patients with concomitant metastasis to other organs or with HER2-negative subtype. Hepatic resection remarkably prolonged survival (SEER: 90 vs. 35 months; JSPH: not reached vs. 31.3 months). In the JSPH cohort, molecular subtype changed in 27.5% of patients during metastasis. CONCLUSIONS:The occurrence of BCLM is affected by age, tumor grade, other organ involvement, and molecular subtype. Survival was improved in BCLM patients with liver-only metastasis, HER2-positive subtype, or those who underwent hepatic resection. The number and molecular characteristics of liver metastasis are important prognostic predictors, and receptor conversion highlights the need for reassessment of therapeutic strategies during metastatic progression.
OBJECTIVE:To synthesize the available evidence on the oncologic outcomes, toxicity, and cosmesis of hypofractionated whole-breast irradiation (HF-WBI) in patients with ductal carcinoma in situ (DCIS) following breast-conserving surgery (BCS). METHODS:A systematic review and meta-analysis was conducted according to PRISMA guidelines. PubMed, Embase, and Web of Science were searched from inception until July 12, 2025. We included studies of DCIS patients treated with BCS followed by HF-WBI (fraction size > 2.0 Gy). Both comparative studies (against conventional fractionation [CF]) and single-arm studies reporting outcomes for HF-WBI alone were included. Pooled incidence rates for outcomes from single-arm studies and pooled hazard ratios (HRs) or odds ratios (ORs) from the limited comparative studies were calculated using random-effects models. RESULTS:Nineteen studies were included. Local control and overall survival were excellent and equivalent between HF-WBI and CF-WBI. The pooled HR for local recurrence comparing ultrahypofractionation to CF was 0.89 (95% CI 0.64-1.24). HF-WBI significantly reduced the odds of acute dermatitis (OR 0.22, 95% CI 0.13-0.35). Late toxicities were infrequent (e.g., telangiectasia: 2%, 95% CI 0%-5%). Good/excellent cosmesis was reported in 90% (95% CI 84%-94%) of patients. CONCLUSION:HF-WBI is a safe and effective treatment for DCIS, achieving oncologic outcomes equivalent to CF while offering improved tolerability, reduced acute skin toxicity, and excellent cosmetic results. These benefits, combined with increased convenience and potential cost savings, support the integration of HF-WBI into standard practice for DCIS.
BackgroundNeoadjuvant chemotherapy (NACT) is an important component in preparing breast cancer patients for surgery. Its impact on postoperative complications, such as wound infections and bleeding, remains unclear. While most studies show no increase in complication rates, factors such as smoking may elevate risk. Understanding surgeons' perspectives on bleeding and related influences is therefore essential.MethodsThis study used a questionnaire on bleeding and wound healing. After ethical approval in Vienna and Burgenland, 33 surgeons were recruited. Data were collected between July and December 2022 through interviews or self-administered questionnaires and analyzed descriptively.ResultsOverall, 63.6% of surgeons reported recognizing NACT-treated patients intraoperatively. Perceptions of blood loss varied, with some noting no difference and others reporting increased bleeding. The influence of tumor size and smoking was debated, with no clear consensus. Most surgeons did not observe prolonged operative times. Challenges in axillary dissection and sentinel lymph node identification were reported, particularly after NACT.ConclusionSurgeons' views on the impact of NACT in breast surgery vary considerably. These findings highlight the complexity of integrating NACT into surgical practice and the need for further research to improve training, patient counseling, and evidence-based guidelines.
OBJECTIVE:This study developed a cuproptosis-related transcriptomic risk score model to predict neoadjuvant chemotherapy (NAC) response in breast cancer (BC) patients and explored its association with the tumor immune microenvironment. METHODS:Analysis of transcriptomic and clinical data from TCGA and GEO revealed differentially expressed cuproptosis-related genes. LASSO-based Cox regression was used to build the risk score. Model performance was evaluated using Kaplan-Meier survival, ROC curves, and GSEA/GSVA in the training cohort and further validated in an independent external cohort. Drug sensitivity was predicted using the oncoPredict tool, and RT-qPCR was used to validate key gene expression. RESULTS:A 10-gene prognostic model was developed based on the identification of 71 cuproptosis-related genes. The risk score correlated with survival outcomes, PAM50 subtypes, tumor stage, and pathologic response. It showed good predictive performance in both training (AUC = 0.719) and testing (AUC = 0.689) cohorts. Key genes (CIRBP, INPP4B, IL6ST, and CCL20) were validated and linked to NAC response. CONCLUSION:The cuproptosis-based risk score model effectively predicts NAC response and may guide personalized treatment in BC. It also reveals the relevance of cuproptosis-related genes in immune modulation and chemotherapy sensitivity.
OBJECTIVE:To explore the clinical efficacy, cosmetic outcome, and safety of comprehensive pharmacotherapy (traditional Chinese medicine + hormone + antibiotic) combined with ultrasound-guided precise lesion resection plus primary microplasty in the treatment of refractory nonpuerperal mastitis (NPM). METHODS:The clinical and pathological data of refractory NPM patients who underwent surgical treatment at our hospital from February 2021 to December 2024 were retrospectively analyzed. The sample size was calculated using a superiority test, and a total of 97 patients were finally included. They were assigned to two groups using a random number table for retrospective stratification assignment (to balance baseline clinical characteristics and reduce selection bias): The control group (45 cases) underwent extended lesion resection combined with fascial flap plasty and nipple-areola correction and the observation group (52 cases) underwent ultrasound-guided precise lesion resection plus primary microplasty. The recurrence rate, breast cosmetic score (Harris score), postoperative psychological status (24-item Hamilton Depression Rating Scale [HAMD-24]), hospital stay, and incidence of complications were compared between the two groups. RESULTS:All surgeries were successfully completed in both groups without serious complications. All patients were followed up for more than 12 months (median follow-up period: 16.8 ± 2.9 months). There were no statistically significant differences in the incidence of postoperative complications [7.7% (4/52) vs. 6.7% (3/45), p = 1], drainage time [(3.5 ± 0.3) d vs. (3.6 ± 0.4) d, t = -1.398, p = 0.166], and hospital stay [(10.7 ± 0.6) d vs. (10.6 ± 0.5) d, t = 0.894, p = 0.373] between the two groups. The recurrence rate of the observation group was lower than that of the control group [0% (0/52) vs. 11.1% (5/45), X2 = 9.836, p = 0.002], and the cosmetic effect and patient satisfaction of the observation group were superior to those of the control group. The HAMD-24 score of the observation group [(7.8 ± 2.9) points] was lower than that of the control group [(12.5 ± 3.8) points], with a statistically significant difference (t = 11.562, p = 0.001). CONCLUSION:For refractory NPM, the combination of comprehensive pharmacotherapy, ultrasound-guided precise lesion resection, and primary microplasty achieves remarkable therapeutic effects, characterized by reduced complication rates and low short-to-long-term recurrence. This integrated traditional Chinese and Western medicine strategy is not only safe and effective but also provides excellent cosmetic benefits for patients.
BackgroundMicrobiota-derived metabolites are increasingly recognized as modulators of systemic immunity and cancer biology. This study investigates how a structurally distinct lipid from Akkermansia muciniphila influences immune transcriptional programs and their connection to breast cancer (BRCA)-associated pathways.MethodsDonor-adjusted reanalysis of PBMC RNA-seq data was performed to identify lipid-responsive transcriptional changes while minimizing interindividual variability. Differential expression was assessed across time points, followed by pathway enrichment and immune gene filtering. Immune cell composition was inferred using deconvolution analysis. Integration with The Cancer Genome Atlas (TCGA)-BRCA datasets enabled tumor immune infiltration profiling and network-based identification of hub genes. ceRNA interactions were refined using correlation-supported datasets and prognostic relevance was evaluated in TCGA and METABRIC cohorts.ResultsTranscriptional variation was primarily driven by the treatment and exposure duration rather than donor effects. A biphasic immune response (IR) was observed, with early suppression followed by progressive activation. Lipid-responsive genes significantly overlapped with BRCA immune signatures and were enriched in metabolic and stress-related pathways. Immune deconvolution revealed shifts in macrophage polarization and cytotoxic cell populations. Network analysis identified key regulators, including ADIPOR1, KLF4, MYC, CXCL10, and ALDH1A1, linked to distinct immune infiltration patterns. ceRNA networks highlighted oncogenic and tumor-suppressive miRNA interactions. A five-gene signature demonstrated moderate prognostic value across cohorts.ConclusionMicrobial lipid signaling induces dynamic immune reprogramming that converges on tumor-relevant pathways, suggesting a systemic immune-mediated link between microbiota and BRCA progression, with potential implications for immune-targeted therapeutic strategies.
BACKGROUND:Adipose tissue is a major stromal component of the breast cancer (BC) tumor microenvironment (TME), playing a crucial role in BC progression. Cancer-associated adipocytes (CAAs), located at the invasive tumor front, undergo significant morphological and functional alterations. This observational case-control study investigated the dedifferentiation trajectory of CAAs and its impact on BC progression. METHODS:Paired tumor and distant normal adipose tissues from 20 BC patients were analyzed. Histological and immunohistochemical analyses were performed to assess morphological changes and marker expressions α-SMA, S100A4, and CD36 in CAAs. RESULTS:CAAs exhibited features consistent with dedifferentiation toward a myofibroblast-like phenotype, marked by expressing α-SMA and S100A4, indicators of myofibroblasts and tumor-associated fibroblasts. Metabolically, CAAs showed increased CD36 expression and histological features compatible with augmented lipolysis and were spatially associated with areas of extracellular matrix (ECM) remodeling. Masson's trichrome staining demonstrated augmented pericellular collagen deposition, accompanied by increased tissue stiffness and enhanced angiogenesis at the tumor-adipose boundary. In addition, nuclear translocation of β-catenin in peritumoral adipocytes implicates the Wnt/β-catenin signaling axis as a potential regulator of adipocyte-mesenchymal transition in this context.
