Exposure to immune stress or lipopolysaccharide (LPS) during critical developmental stages like puberty may lead to gut microbiome dysbiosis and epigenetic dysregulation in mammary glands, affecting gene expression and potentially elevating breast cancer susceptibility in adulthood. Although LPS's adverse impacts on intestinal and brain functions are well-documented, its effects on mammary glands remain underexplored. Using an immunocompetent BALB/c mouse model, we administered an acute LPS dose (1.5 mg/kg body weight) during puberty. The study evaluated the long-term consequences of LPS exposure alone and combined with AHCC (Lentinula edodes cultured extract, 2 g/kg body weight/day) on DNA methylation patterns, cytokine profiles, and microRNA expression in mammary glands at 9 weeks of age. Analyses included DNA methylation sequencing, multiplex immunoassays, quantitative PCR, and image processing. Pubertal LPS exposure produced persistent molecular dysregulation in mammary glands, including differential DNA methylation (> 5% change vs. control; FDR-adjusted p < 0.05), elevated inflammatory mediators, and altered microRNA expression. Differentially methylated regions were enriched in regulatory features, with decreased methylation at transcription start sites, promoters, and 5' UTRs of genes implicated in mammary development and oncogenic signaling (including Vav3, Pdgfa, Pdgfc, Jag2, Hras, Ksr1, Il2rb, Il17b, and Il17rb) in the LPS group, whereas the AHCC + LPS group exhibited a shift toward hypermethylation at these loci (approximately 5%-10% decrease). Inflammatory profiling showed increased IL-17A/F (∼2-fold vs. control; p < 0.05), while microRNA analyses indicated reduced let-7a/c (∼30% vs. control; p < 0.05). Notably, miR-130a and miR-34a increased ∼1.5-fold across all treatment groups relative to control. Pubertal LPS exposure induces enduring epigenetic and inflammatory changes in mammary glands that may heighten breast cancer risk. AHCC's mitigating role indicates potential for dietary interventions to counteract these effects.

Adenomyoepithelioma (AME) is a rare breast tumor characterized by the biphasic proliferation of epithelial and myoepithelial cells. Due to its rarity, data on its imaging characteristics-particularly magnetic resonance imaging (MRI) findings-remain limited. This study aimed to evaluate the radiological features of AME and assess the diagnostic contribution of multiparametric imaging. This retrospective study included 11 patients pathologically diagnosed with AME between 2013 and 2024 who underwent mammography, ultrasound (US), and MRI prior to diagnosis. Lesions were evaluated according to BI-RADS criteria: mammography (shape, margin, density, and calcifications); US (shape, margin, orientation, echogenicity, posterior features, vascularity, and elastography); and MRI (morphology, T2 signal intensity, ADC values, and enhancement kinetics). The most common mammographic finding was an isodense oval or round mass with partially obscured margins (36.4%). No lesions demonstrated irregular shape or suspicious microcalcifications. On US, 90.9% of lesions were oval/round with circumscribed (45.5%) or indistinct (54.5%) margins. All lesions were hypoechoic and vascular; 71.4% exhibited soft elasticity on strain elastography. On MRI, 54.5% were hyperintense on T2 weighted images (T2WI) with circumscribed margins. ADC values ranged from 1.00 to 1.434 × 10-3 mm2/s (mean 1.273 × 10-3 mm2/s). Enhancement kinetics demonstrated Type I in 3/11, Type II in 3/11, and Type III in 5/11 lesions. Although AME often demonstrates benign morphological features, it is frequently categorized as BI-RADS 4 due to vascular and kinetic characteristics that raise suspicion for malignancy. Our findings suggest that relatively low ADC values further contribute to this suspicious imaging profile. However, the absence of suspicious microcalcifications, an oval or round shape, and hyperintensity on T2WI may aid in the differential diagnosis. Given the malignant potential of these lesions, wide local excision with negative margins is essential, and radiological findings play a crucial role in guiding the need for pathological confirmation.

To investigate cardiovascular disease (CVD) mortality among patients with different breast cancer (BC) subtypes to assess its implications for long-term survival. In total, 423,758 BC patients were included in this study utilizing data from the Surveillance, Epidemiology, and End Results 17 Registries Database (2010-2020). Competing risk curves were utilized to assess whether the cumulative CVD mortality surpassed the cumulative BC mortality. Multivariate competing risk models were used to explore potential factors associated with CVD mortality. Standardized mortality ratios (SMRs) were calculated to investigate CVD mortality in comparison to the general population. In total, 5863 BC patients died from CVD during follow-up time, accounting for 10.0% of all deaths (56,856). The number of deaths and the percentage of all deaths among patients died from CVD for luminal A, luminal B, HER-2 enriched, and triple-negative subtype were 4160 (12.2%), 615 (9.7%), 291 (7.7%), and 797 (6.2%), respectively. After 9 years, BC mortality remained over 10% higher than CVD mortality for luminal A and B subtypes, but the difference was under 10% for HER-2-enriched and triple-negative subtypes. HER-2-enriched and triple-negative BC patients aged 55-84 had higher CVD mortality compared to the general population. Triple-negative BC was independently associated with increased CVD mortality compared with luminal A (HR 1.103 [95% CI: 1.016-1.199]). Patients with the triple-negative subtype have a high risk of CVD mortality. This underscores the need for enhanced surveillance and targeted cardiovascular interventions for these patients to improve their long-term health outcomes.

Background: The clinical impact of HER2-low status on the efficacy of cyclin-dependent kinase 4/6 inhibitor (CDK4/6i). Therapy in patients with hormone receptor-positive (HR+), HER2-negative metastatic breast cancer (MBC) remains unclear.Methods: We conducted a multicenter, retrospective analysis including 212 female patients with HR+/HER2−MBC treated with CDK4/6is between 2018 and 2022. Patients were classified as HER2-zero or HER2-low based on immunohistochemistry results. Progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were compared between the two groups.Results: Median PFS was 16.0 months in the HER2-low group and 13.9 months in the HER2-zero group (p=0.40). In first-line therapy, PFS was numerically longer in the HER2-low group (18.6 vs. 14.9 months; p=0.26) although this was not statistically significant. ORR was 71.4% in HER2-low and 62% in HER2-zero patients, and DCR was 86.6% and 82%, respectively (both p > 0.05). Subgroup analyses showed that within the HER2-low group, patients with ≥ 2 metastatic sites had significantly shorter PFS compared with those with a single site (14.1 vs. 20.2 months; p=0.02), and the presence of visceral metastases was associated with poorer PFS (p=0.003). Overall survival (OS) data were immature, with only 24.6% of the patients deceased at the time of analysis.Conclusion: HER2 status did not significantly impact treatment outcomes with CDK4/6i in HR+/HER2-negative MBC patients. However, subgroup analyses indicated that metastatic burden, particularly the number of metastatic sites and the presence of visceral disease, may adversely influence PFS. These findings highlight the need for further validation in larger prospective studies.

Neoadjuvant therapy before surgery offers varying benefits as a well-established treatment option for breast cancer. This study specifically evaluated the effectiveness of neoadjuvant endocrine therapy (NET), neoadjuvant chemotherapy (NCT), and neoadjuvant chemo-endocrine therapy (NCET) in patients with estrogen receptor (ER)-positive breast cancer. This meta-analysis was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Electronic searching was conducted to retrieve articles from databases including PubMed, Cochrane Library, EMBASE, CNKI, and Wanfang. The primary outcome measured by odds ratios (ORs) with 95% confidence intervals (CIs) focused on assessing pooled effect sizes. Random-effects or fixed-effect models were conducted according to the existence of statistical heterogeneity. A total of 15 eligible articles were included in the analysis. The results indicated clinical response (CR) (OR = 0.54; 95% CI = 0.41 to 0.73; I 2 = 39.6%) and clinical complete response (cCR) (OR = 0.31; 95% CI = 0.12 to 0.85; I 2 = 68.0%) after NET was significantly higher than NCT. However, no significant difference was shown in pathological complete response (pCR) (OR = 0.49; 95% CI = 0.23 to 1.04; I 2 = 0.0%) and breast-conserving surgery (BCS) (OR = 0.49; 95% CI = 0.23 to 1.04; I 2 = 0.0%). The combined paradigm of NCET presented no significant improvement compared with monotherapy of NET or NCT. Overall, both NET and NCT are effective neoadjuvant treatment options for patients with ER+ breast cancer. More explicit clinical decision indicators need to be further clarified. And NCET does not offer additional benefits over NET or NCT in patients with ER+ breast cancer.

Aim: To investigate the association between mammographic extratumoral signs, specifically their subclassifications, of nonspiculate and noncalcified masses (NSNCMs) and prognostic factors in breast cancer. Materials and Methods: This retrospective study analyzed imaging and pathological data from 374 patients, categorizing extratumoral signs into structural abnormalities (parenchymal and trabecular) and halo, while also undergoing subclassification. The focus prognostic factors were achieved through screening. Then, univariate and multivariate analyses were performed. Correlation analysis was also employed to determine the relationship between subclassifications and prognostic factors. Results: Lymphovascular invasion (LVI), Ki-67 levels, and stromal tumor-infiltrating lymphocytes (sTIL) levels were identified as the focus prognostic factors. Among tumor signs, only tumor margin was associated with sTIL levels. Extratumoral trabecular signs exhibited a significant correlation with LVI (OR = 2.5, p=0.007) and Ki-67 levels (OR = 1.23, p=0.001). Specifically, the parallel sign showed a positive correlation with LVI (p=0.009, r = 0.134), while the reticular sign displayed a positive correlation with Ki-67 levels (p=0.009, r = 0.134). Extratumoral parenchymal signs were found to be an independent predictor for sTIL levels (OR = 0.64, p < 0.001), with a negative correlation observed between the contraction sign and sTIL levels (p < 0.001, r = -0.185), as well as between the atrophy sign and sTIL levels (p=0.046, r = -0.103). Conclusion: Specific extratumoral structural abnormalities of mammographic malignant NSNCMs showed a significant correlation with prognostic factors in breast cancer, warranting increased attention in research and clinical practice.

Background: Breast carcinoma is divided into at least 21 separate histologies, according to the 2019 World Health Organization (WHO) classification. The present study is dedicated to a 5% or rarer group of all breast cancer cases. Method: In this study, we retrospectively considered the data of 4550 patients operated on for breast carcinoma at the Ankara Oncology Training and Research Hospital of the University of Health Sciences between January 2018 and February 2024. Of those cases, 401 were discovered to have rare breast cancer types. We also explored the cases by clinicopathological features, overall survival (OS), and disease-free survival (DFS). Results: Our findings revealed a total of 10 rare breast cancer types in patients explored: mucinous carcinoma, micropapillary carcinoma, papillary group carcinomas, metaplastic carcinoma, neuroendocrine carcinoma, tubular carcinoma, cribriform carcinoma, apocrine carcinoma, acinic cell carcinoma, and secretory carcinoma. While mucinous, tubular, cribriform, papillary group carcinomas, micropapillary, and secretory carcinomas are described as types associated with good prognosis, metaplastic, neuroendocrine, apocrine, and carcinomas are described as types associated with relatively poor prognosis. Conclusion: Scrutinizing the clinicopathological features of rare breast cancer types altogether may be the distinct contribution of this paper to the relevant literature and future research.

BackgroundAngiosarcomas (ASs) are a heterogeneous subtype of soft tissue sarcomas. They can be subdivided into primary and secondary AS, with secondary AS being predominant, particularly those following radiotherapy. The aim of this study was first to analyze our patient cohort on a descriptive level and then to identify possible risk factors with regard to one and 5-year survival using logistic regression.MethodsThe study was designed as a retrospective, single-center cohort study. All patients with histologically confirmed AS over 18 years of age were included in the study. Binary logistic regression was used for univariate analysis screening of continuous or dichotomous variables, respectively. For multivariate analysis, binary multivariate logistic regression was performed to assess independent associations between chosen variables and AS.ResultsA total of 39 patients were included in this study. 14 (35.9%) had primary and 25 (64%) had secondary AS. Women were more frequently affected (76.9%) than men (23.1%). The 1-year survival rate was 87.2%, and the 5-year survival rate was 51.3%. In the logistic regression analyses, nicotine consumption and a history of carcinoma were identified as significant factors influencing the 1-year survival rate. For the 5-year survival rate, only breast cancer was found to be a significant influencing factor in the univariate analysis. Based on univariate logistic regression, all variables with a p value of < 0.1 were chosen to be included into multivariate analysis. The multivariate analysis showed diabetes mellitus (p=0.067) with an association to influence the 5-year survival rate.ConclusionsWe were able to show that the proportion of secondary ASs is predominant. These occur after radiation treatment of the breast. Diabetes mellitus may be associated with reduced 5-year survival, although this finding did not reach statistical significance and requires further investigation. Due to its small sample size, this study should be regarded more as hypothesis-generating.

Objective: To investigate the efficacy of microwave ablation (MVA) combined with Chai Hu Qing Gan Tang (CHQGT) for idiopathic granulomatous mastitis (IGM).Methods: 480 patients were divided into the CHQGT combination group (CHQGT + MVA), corticosteroid combination group (glucocorticoids + MVA) and control group (glucocorticoids), with 160 cases in each group. Data on patient information, treatment effects, adverse effects and breast appearance were collected. Network pharmacology was used to identify the effective active ingredients and target information of CHQGT. The Gene Cards database was used to obtain the relevant targets of IGM, and the drug-component–common target relationship network was constructed using Cytoscape 3.9.1 software.Results: All treatment groups showed significant differences in Visual Analog Scale score, Hamilton Depression Rating Scale score, Hamilton Anxiety Rating Scale, mass size and the total effective rate (p < 0.001). There was a statistically significant difference in the rate of excellent breast shape between the three groups after treatment (p < 0.001), with the rate higher in the CHQGT liver decoction combined with glucocorticoids treatment group compared with the control group. There was a statistically significant difference in the incidence of adverse reactions and recurrence rate between the three groups within 2 years after treatment (p < 0.001), with the incidence of adverse reactions and recurrence rate higher in the control group than in the glucocorticoid combination and CHQGT decoction combination groups. Network pharmacology identified 199 active ingredients and 23 drug-disease targets of CHQGT. The molecular docking results showed that the main active components screened had good binding activity with their corresponding target proteins.Conclusion: The combination of CHQGT and MWA is comparable in overall therapeutic efficacy to the combination of glucocorticoids and MWA. However, the CHQGT and MWA combination is superior in reducing lump size, alleviating patient pain and accelerating recovery.

Introduction: Idiopathic granulomatous mastitis (IGM) is a benign, chronic inflammatory disease with no effective treatment and high relapse rate. The pathophysiology is poorly understood. Tinosporin, an immunomodulator obtained from Tinospora cordifolia, is known to be useful in treating immune-mediated diseases. We report our experience of using Tinosporin for IGM and the effectiveness of this "steroid-free" regimen. Methods: We analysed the clinicopathological characteristics of patients diagnosed with IGM on histopathology during January 2018 and December 2022. Tinosporin tablet (500 mg Guduchi stem extract) was prescribed for 3-6 months; data were collected from electronic medical records and analysed in SPSS v-29. Results: Of 315 patients, 132 had complete clinical records. Median age was 39 years (25-77), and 107 (81.7%) were premenopausal. Seventy-eight (59.09%) had clinical suspicion of malignancy. On imaging, 84 (63.64%) were BIRADS 4/5 lesions. Empirical broad-spectrum antibiotics were prescribed to 101 patients. Tinosporin tablets were prescribed to 91 patients. Symptomatic response was seen in 72 (79.12%). Five patients did not achieve response, while 14 patients (15.38%) were lost to follow-up. At a median follow-up of 36 months (14-62 months), only 2 patients on Tinosporin had recurrence. None of the patients needed surgical intervention other than diagnostic biopsy or control of infection, and none received steroids. Conclusion: IGM is a benign, often self-limiting disorder. However, it mimics malignancy in 60% cases, and histology clinches the diagnosis. We report the efficacy of steroid-free management of IGM with immunomodulatory herbal origin phytopharmaceutical drug Tinosporin. It is safe, inexpensive and effective. Large volume excisions or mastectomies can be reserved for severe and refractory cases.