Search Results (2,248)

Background/Objectives: Pancreatic metastases are uncommon, and local treatment is reserved for selected patients with limited disease. Surgery remains the standard option when feasible, but may be inappropriate in patients with small, multifocal, anatomically challenging, or medically high-risk lesions. This study evaluated endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) as an organ-preserving local treatment for pancreatic metastases. Methods: Consecutive adult patients undergoing EUS-RFA for histologically confirmed pancreatic metastases at a tertiary endoscopy center between February 2021 and December 2025 were included. All cases were discussed in a multidisciplinary setting. EUS-RFA was performed using a 19G internally cooled RFA needle under real-time EUS guidance. The primary endpoint was initial complete radiological response, defined as complete ablation on first follow-up imaging. Secondary endpoints included technical success, radiological response, repeat EUS-RFA, adverse events, follow-up, and survival. Results: Eleven patients were treated; the mean age was 72.4 ± 6.4 years, and 7/11 (63.6%) were women. Primary tumors included renal cell carcinoma in 7/11 (63.6%), breast cancer in 2/11 (18.2%), melanoma in 1/11 (9.1%), and colorectal cancer in 1/11 (9.1%). Median lesion size was 10.5 mm. Technical success was achieved in 11/11 patients (100%). Initial complete radiological response at first follow-up was observed in 10/11 patients (90.9%); the remaining patient achieved complete response after repeat EUS-RFA. Adverse events occurred in 3/11 patients (27.3%), all mild and conservatively managed. No bleeding, perforation, pancreatic duct stenosis, pancreatic collection, or procedure-related death occurred. Median follow-up was 338 days. Conclusions: EUS-RFA appears feasible and generally well tolerated in carefully selected patients with pancreatic metastases, particularly small, well-visualized lesions when surgery is not feasible or an organ-preserving strategy is preferred. Larger prospective multicenter studies are needed. Although formal subgroup comparisons were not possible in this small cohort, lesion size, anatomical location, and primary tumor biology are likely to influence technical difficulty, local response, and the need for staged or repeat treatment. Full article

Background and Objectives: Breast cancer is the leading oncological diagnosis among women in Kazakhstan, yet a substantial proportion of cases are still detected beyond the earliest stages, particularly in peripheral regions such as Aktobe. Despite a national mammography screening programme covering women aged 40–70 years since 2018, structural differences in access to early diagnosis—related to geography, socioeconomic circumstances, and the diagnostic pathway—may compromise outcomes. We aimed to identify factors independently associated with early-stage presentation and to characterise the temporal pattern of early-stage presentation without assuming a monotonic trend. Methods and Materials: We conducted a retrospective, population-based analytical study of all confirmed breast cancer cases (ICD-10 C50) registered in the Aktobe regional cancer registry and diagnosed between 1 January 2015 and 31 December 2025 (n = 2232). The outcome was early-stage presentation, defined literally as Stages I–IIa at diagnosis, with Stages IIb–IV as the comparator; this is a stage-at-presentation classification and is not intended to indicate surgical operability or treatment sequence. Multivariable logistic regression estimated adjusted odds ratios (aORs). Two models were used: Model A included age, sex, residence, administrative nationality, employment/social status, and calendar year; Model B additionally included the diagnostic pathway, which may lie on the causal pathway between structural determinants and stage. Calendar year was modelled as a categorical variable, and a complementary phase-based model (2015–2017, 2018–2019, 2020–2022, 2023–2025) was fitted. A residence-by-year interaction; a multinomial sensitivity analysis separating Stages IIb, III, and IV; discrimination (AUC, Brier score); and calibration (Hosmer–Lemeshow test, calibration plot) were also assessed. Results: Of 2232 patients (99.1% female; mean age 57.0 ± 12.5 years), 1323 (59.3%) presented at Stages I–IIa. In Model A, rural residence (aOR 0.77, 95% CI 0.64–0.93; p = 0.006), unemployment relative to employment (aOR 0.69, 95% CI 0.52–0.90; p = 0.007), Russian administrative nationality (aOR 0.64, 95% CI 0.50–0.82; p < 0.001), and other non-Kazakh nationalities (aOR 0.73, 95% CI 0.58–0.94; p = 0.012) were independently associated with lower odds of Stage I–IIa presentation. In Model B, patient-initiated (self-referral) presentation was associated with lower odds relative to clinical examination room detection (aOR 0.46, 95% CI 0.30–0.72; p < 0.001), whereas organised screening was not significantly associated (aOR 1.52, 95% CI 0.95–2.43; p = 0.082). The calendar-year pattern was clearly non-linear (categorical vs. linear year: likelihood-ratio χ² = 76.1, df = 9, p < 0.001): odds of Stage I–IIa presentation peaked in 2018 (aOR 2.49, 95% CI 1.57–3.93 vs. 2015), were lowest in 2022 (aOR 0.64, 95% CI 0.42–0.97), and partially recovered thereafter. In the phase-based model (reference 2015–2017), the aORs were 1.62 (95% CI 1.22–2.15) for 2018–2019, 0.54 (95% CI 0.41–0.69) for 2020–2022, and 0.62 (95% CI 0.46–0.84) for 2023–2025. Model discrimination was limited (AUC 0.648, 95% CI 0.625–0.671; Brier score 0.226) with acceptable calibration (Hosmer–Lemeshow χ² = 8.38, df = 8, p = 0.40). Conclusions: In this registry-based cohort, rural residence, unemployment, non-Kazakh administrative nationality, and patient-initiated presentation were independently associated with lower odds of early-stage breast cancer presentation. The temporal pattern was non-monotonic, with the highest odds around the 2018 screening expansion, a marked reduction during 2020–2022, and only partial recovery thereafter. These are observational associations rather than causal or programme-evaluation findings; they should be interpreted as hypothesis-generating and require confirmation with screening-process, service-capacity, and patient-level access data. Full article

Liquid biopsy has emerged as a transformative approach in modern oncology, offering minimally invasive access to tumor-derived biomarkers through the analysis of circulating tumor DNA, cell-free DNA, and extracellular vesicles such as exosomes. Unlike conventional tissue biopsies, liquid biopsy enables real-time monitoring of tumor dynamics, molecular heterogeneity, treatment response, and the development of therapeutic resistance. Recent advances in ultra-sensitive molecular technologies, including digital droplet polymerase chain reaction, next-generation sequencing, methylation profiling, and fragmentomic analysis, have substantially improved the sensitivity and specificity of circulating nucleic acid detection, facilitating their integration into precision cancer medicine. ctDNA analysis has demonstrated significant clinical utility across multiple malignancies, including lung, breast, colorectal, pancreatic, and prostate cancers, particularly in the identification of actionable genomic alterations, minimal residual disease, and mechanisms of acquired resistance. In parallel, cell-free DNA provides broader insights into tumor biology and systemic genomic alterations, while exosomes contribute additional layers of molecular information through the transport of nucleic acids, proteins, and signaling molecules involved in intercellular communication and tumor microenvironment modulation. The integration of artificial intelligence and machine learning approaches further enhances the interpretative power of liquid biopsy-derived datasets and supports the development of personalized therapeutic strategies. Despite these advances, important challenges remain, including low tumor fraction in early-stage disease, biological and technical variability, clonal hematopoiesis-associated false positives, assay standardization, and cost-effectiveness considerations. Nevertheless, the expanding clinical applicability of liquid biopsy technologies positions them as essential components of contemporary precision oncology. This review summarizes the biological foundations, analytical methodologies, current clinical applications, technological innovations, and future perspectives of circulating tumor DNA, cell-free DNA, and exosome-based liquid biopsies in cancer diagnosis, monitoring, and personalized treatment strategies. Full article

Background/Objectives: Breast cancer (BC) remains the most frequently diagnosed malignancy among women worldwide, and patient outcome is strongly influenced by disease stage at diagnosis. Although imaging-based screening has improved early detection, its performance may be reduced in dense breast tissue and is associated with false-positive findings. In addition, tissue biopsy is invasive and unsuitable for longitudinal disease monitoring. Liquid biopsy (LB) has emerged as a minimally invasive approach for detecting tumor-derived material in peripheral blood. However, early-stage tumors typically exhibit low tumor burden and limited biomarker shedding, generating weak systemic signals that challenge reliable detection. This review examines current and emerging LB biomarkers for early BC detection. Methods: A comprehensive review of recent literature was conducted focusing on circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), extracellular vesicles (EVs), circulating RNAs, proteins, and other blood-based biomarkers associated with early BC. Studies addressing biomarker biology, detection technologies, clinical applications, and methodological limitations were critically evaluated. Results: ctDNA, CTCs, EVs, circulating RNAs, proteins, and additional blood-based biomarkers capture distinct aspects of tumor biology and disease evolution. ctDNA enables the analysis of tumor-specific mutations, methylation patterns, and fragmentation profiles, whereas CTCs provide direct cellular and phenotypic information despite their rarity and marked epithelial–mesenchymal plasticity. EVs offer increased molecular stability and actively participate in tumor progression, immune modulation, and metastatic niche formation. Nevertheless, low biomarker abundance, biological heterogeneity, technical variability, and background biological noise continue to limit analytical performance, particularly in early-stage disease. Current evidence further suggests that no single biomarker consistently provides sufficient sensitivity and specificity for reliable early BC detection. Conclusions: LB represents a promising strategy for non-invasive early BC detection. Future clinical implementation will likely depend on integrated multi-analyte approaches that combine complementary genomic, transcriptomic, proteomic, and cellular information, supported by multi-omics technologies and artificial intelligence-based analytical frameworks. Full article

Background/Objectives: Docetaxel is a frontline chemotherapeutic agent for breast cancer; however, therapeutic resistance remains a major clinical challenge. Emerging evidence suggests that chemotherapy-induced adaptive phosphorylation events can promote survival signaling and contribute to drug resistance. However, the phosphoproteomic mechanisms underlying docetaxel-induced adaptive responses remain poorly characterized. Methods: We performed integrated quantitative proteomic and phosphoproteomic profiling in breast cancer cells following docetaxel exposure. Candidate kinases associated with phosphorylation remodeling were identified and validated using TCGA-BRCA and CPTAC clinical datasets. The functional significance of PAK4 phosphorylation was validated using phosphomimetic and phospho-deficient mutants, pharmacological inhibition, and assessment of microtubule stabilization. Results: Integrated phosphoproteomic analysis revealed extensive phosphorylation remodeling following docetaxel treatment and identified PAK4 as a candidate kinase associated with the adaptive response. Analysis of the CPTAC phosphoproteomic dataset showed that phosphorylation of PAK4 at S474 was elevated in breast cancer tissues, increased with tumor stage, and was associated with poorer overall survival. In breast cancer cells, docetaxel induced phosphorylation of PAK4 at S474 without altering total PAK4 expression. Functionally, phosphomimetic PAK4 (S474D) reduced docetaxel sensitivity, whereas phospho-deficient PAK4 (S474A) enhanced drug sensitivity. Pharmacological inhibition of PAK4 using LCH-7749944 significantly enhanced the inhibitory effect of docetaxel on cell viability and increased apoptosis in breast cancer cells. Mechanistically, PAK4 inhibition enhanced docetaxel-induced microtubule stabilization, as evidenced by increased α-tubulin acetylation and accumulation of stabilized microtubule structures. Conclusions: Our study demonstrates that docetaxel induces global phosphorylation network reprogramming in breast cancer cells and identifies PAK4 S474 phosphorylation as a key determinant of docetaxel sensitivity. Inhibition of PAK4 enhances microtubule stabilization and improves the efficacy of docetaxel, providing a potential combinatorial strategy to overcome taxane resistance. Full article

Background and Objectives: Over recent decades, germline genetic testing has become increasingly integrated into breast cancer care, yet its precise effect on the timing of surgical workflows remains incompletely defined. This study investigates the implementation of nationally reimbursed genetic testing programs and examines how the scheduling of multigene germline testing relates to surgical timing. Materials and Methods: In this retrospective cohort analysis, we examined 502 breast cancer cases from the institutional registry of the “Ion Chiricuță” Oncology Institute (IOCN), with a mean age of 52 years, a high rate of neoadjuvant therapy (82.3%) and a majority of them in T2 (52%) and N1 (43%), N2 (29%) clinical stage: 263 patients from an earlier private-practice pay testing era (pre-reimbursement) as a comparison sample and 239 patients from the period when reimbursement programs were in operation. We then evaluated the benefits of state-funded genetic testing initiatives, computing three intervals: diagnosis to genetic test, genetic test to surgery, and diagnosis to surgery. Patients were categorized by timing of multigene testing (preoperative vs. postoperative), receipt of neoadjuvant systemic therapy (NACT), mutation status, and funding source for testing (national PNS program funded by the Romanian Ministry of Health; PNRR European Recovery and Resilience Facility funds; or self-funded private testing). Nonparametric statistics (Mann–Whitney U, Spearman correlation) and effect-size metrics (Cliff’s delta, Theil–Sen slope) were employed. Results: The median diagnosis-to-surgery interval was 203 days (IQR 179–230). Patients tested preoperatively had longer intervals than those tested postoperatively (216 vs. 182.5 days; p = 0.000153; Cliff’s δ = −0.486), a pattern driven by shared pathways involving NACT rather than by testing-induced delays. NACT was the principal determinant of surgical timing (211 vs. 43 days; p = 302.55 × 10⁻¹¹). Within the preoperative subgroup, time to multigene testing correlated strongly with time to surgery (Spearman ρ = 0.54; p = 4.75 × 10⁻⁷; Theil–Sen slope = 0.37, 95% CI = 0.22–0.53). However, the no-NACT group included only four patients. The presence of a pathogenic variant did not significantly change surgical timing (p = 0.982). The PNS national reimbursement program achieved the highest preoperative integration rate for multigene genetic testing after adjustment for NACT confounder (76.7%), outperforming PNRR (61%) and private practice (56%). Conclusions: While genetic testing timing correlates with surgical workflow, neoadjuvant systemic therapy pathways and program structure exert greater influence than testing per se. Structured national programs enhance preoperative testing uptake without causing delays beyond those inherent to NACT pathways. Full article

Background/Objectives: Older women with breast cancer carry a high burden of frailty, depressive symptoms and cognitive complaints, yet how these domains relate to one another in routine clinical practice remains incompletely understood. We examined the prevalence of positive frailty screening and its association with patient-reported cognitive function and asked whether depressive symptoms account for the apparent link between the two. Methods: We analyzed 314 women aged 65 years or older with stage IIB–IIIC breast cancer who underwent a standardized geriatric assessment. Measures included the G8 screening tool, Vulnerable Elders Survey-13 (VES-13), Geriatric Depression Scale (GDS), Instrumental Activities of Daily Living (IADL), cognition and quality of life (FACT-Cog, FACT-G, and EORTC QLQ-C30). Associations were examined using correlation analyses, group comparisons, and multivariable linear regression. Results: Mean age was 72.9 years. A positive frailty screen (G8 ≤ 14) was present in 295 patients (93.9%), and 102 patients (32.5%) screened positive for depressive symptoms (GDS ≥ 5). G8 screening score correlated strongly with patient-reported cognitive function (Pearson r = 0.80, p < 0.001), and patients with a positive frailty screen reported lower FACT-Cog scores than those with a negative screen (113.0 vs. 129.0, p < 0.001). In multivariable analysis adjusted for age and G8 score, depressive symptoms emerged as the strongest independent correlate of FACT-Cog (β = −0.89, p < 0.001; model R² = 0.90), whereas G8 screening score was no longer independently associated (p = 0.16). Patients with depressive symptoms had more than double the VES-13 vulnerability score of those without (7.8 vs. 3.6, p < 0.001). Overall geriatric assessment profiles were generally comparable across the three exploratory treatment-era cohorts. Conclusions: In this cross-sectional analysis of older women with locally advanced breast cancer, depressive symptoms were the strongest independent correlate of patient-reported cognitive function. Incorporating a brief depression screen into routine geriatric assessment may represent a clinically actionable target that deserves further evaluation. Full article

Background/Objectives: Triple-negative breast cancer (TNBC) is an aggressive subtype in which neoadjuvant chemotherapy plays an important role in initial treatment. Pathological complete response (pCR) following neoadjuvant therapy can serve as a surrogate marker for long-term survival. Our study aimed to evaluate the value of the Pan-Immune-Inflammation Value (PIV), Neutrophil-to-Lymphocyte Ratio (NLR), and Platelet-to-Lymphocyte Ratio (PLR), measured at multiple time points, in predicting pCR. Methods: We retrospectively included 89 patients with non-metastatic TNBC treated with neoadjuvant chemotherapy with or without immunotherapy, followed by surgery. Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Pan-Immune-Inflammation Value (PIV) were calculated at baseline, before the second treatment cycle, and at the pragmatic pre-transition assessment before a subsequent treatment phase, when applicable. The primary endpoint was pCR, defined as ypT0N0. Multivariable logistic regression models included age, Ki-67, clinical T stage, and tumor grade. Biomarker-extended models were compared with the clinical model on identical complete-case samples. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), likelihood ratio testing, calibration measures, Brier scores, and bootstrap internal validation with 2000 resamples. Results: pCR was achieved in 25 of 89 patients (28.1%). Baseline platelet counts were lower in patients with pCR than in those without pCR (median 246 × 10³/µL vs. 272 × 10³/µL; p = 0.021). At the pre-transition assessment, patients with pCR had lower monocyte counts (0.20 × 10³/µL vs. 0.57 × 10³/µL; p = 0.048) and lower PIVs (378.9 vs. 746.0; p = 0.011). Baseline PIV did not improve the clinical model. On the same 83-patient sample, adding baseline platelet count increased the apparent AUC from 0.751 to 0.807; however, the bootstrap 95% confidence interval (CI) for the AUC difference included zero (−0.003 to 0.128). On the same 75-patient sample, adding pre-transition PIV increased the apparent AUC from 0.735 to 0.798, with a bootstrap 95% confidence interval for the AUC difference of 0.005 to 0.142. The optimism-corrected AUC for the overall clinical model was 0.716, indicating lower internally validated performance than suggested by the apparent AUC. A smaller absolute increase in PIV from baseline to the pre-transition assessment was associated with pCR, but this finding was definition-dependent and remained exploratory. Conclusions: Standalone baseline markers have limited utility in predicting pCR in non-metastatic TNBC. Pre-transition PIV showed the most consistent incremental association with pCR beyond conventional clinical variables, whereas the added value of baseline platelet count was uncertain and baseline PIV provided no incremental benefit. Because of the retrospective design, limited sample size, treatment heterogeneity, and evidence of model optimism, these findings should be regarded as hypothesis-generating and require external validation. Full article

Background/Objectives: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by substantial biological heterogeneity and variable clinical outcomes. Reliable prognostic tools are needed to improve risk stratification following neoadjuvant chemotherapy (NACT). This study aimed to evaluate the association of the Clinical–Pathologic Stage, Estrogen/Grade (CPS-EG) score with pathological complete response (pCR) and survival outcomes in patients with locally advanced TNBC treated with NACT. Methods: In this multicenter retrospective cohort study, 690 patients with locally advanced TNBC treated with NACT between 2010 and 2024 at 25 oncology centers were included. Patients were categorized according to CPS-EG score (≤3 vs. >3). Associations between CPS-EG score, clinicopathological characteristics, pCR, disease-free survival (DFS), and overall survival (OS) were analyzed. Survival outcomes were evaluated using Kaplan–Meier and Cox regression analyses. Results: Patients with a CPS-EG score > 3 had significantly lower pCR rates and higher recurrence rates compared with those with a CPS-EG score ≤ 3 (p < 0.001 for both). Five-year OS rates were 83.7% and 54.1% in the CPS-EG ≤ 3 and > 3 groups, respectively, while the corresponding five-year DFS rates were 76.4% and 51.9% (p < 0.001 for both). In the multivariable analysis, CPS-EG > 3 remained independently associated with worse OS (HR 1.46, 95% CI 1.08–1.98, p = 0.015) and DFS (HR 1.73, 95% CI 1.26–2.38, p < 0.001). Conclusions: A higher CPS-EG score is associated with a lower likelihood of achieving pCR and poorer long-term survival outcomes in patients with locally advanced TNBC treated with NACT. The CPS-EG score represents a simple and readily available tool that may support risk stratification and clinical decision-making in routine practice. Full article

Background: Metronomic chemo-endocrine therapy combining fulvestrant with metronomic VEC (vinorelbine, cyclophosphamide, and capecitabine)—the FulVEC regimen—demonstrated promising activity in an initial cohort of 38 patients with advanced ER+/HER2− breast cancer (JCM 2023). Here, we present an extended analysis of 72 consecutive patients, with a focus on a novel hypothesis: that treatment-emergent adverse events (AEs) requiring dose modification serve as a surrogate for sufficient pharmacological exposure in metronomic combination chemotherapy. Methods: Retrospective analysis of 72 consecutive patients with metastatic ER+/HER2− breast cancer treated with FulVEC at Jagiellonian University Hospital between 2018 and 2024. Efficacy endpoints included progression-free survival (PFS), overall survival (OS), and biochemical response, as assessed by CA15-3 dynamics. Patients were stratified by AE severity requiring intervention (grade 0: no modification; grade 1: dose reduction; and grade 2: treatment delay). The association between AE grade and efficacy outcomes was assessed using Spearman’s correlation, the log-rank test, and the chi-square test. Results: The median PFS was 8.5 months, and the median OS was 18.0 months. The biochemical benefit rate (any CA15-3 decline) was 81.6%. No statistically significant differences in efficacy were observed according to prior exposure to CDK4/6 inhibitors, fulvestrant, or cytotoxic components of the FulVEC regimen. A monotonic dose–response relationship was observed across AE grade categories: non-progression rates increased from 73.2% (grade 0) to 84.2% (grade 1) and 91.7% (grade 2); biochemical benefit rates from 68.4% to 90.9% and 100.0%; and median CA15-3 reduction deepened from −34% to −44% and −52%, respectively (Spearman r = 0.258 and p = 0.043 for AE grade vs. treatment duration). Formal log-rank comparisons of PFS and OS across the three AE-grade categories did not reach statistical significance (p = 0.583 and p = 0.743, respectively), reflecting the limited size of the treatment-delay subgroup (n = 12); the dose–response signal should, therefore, be regarded as exploratory. No patient required permanent treatment discontinuation due to toxicity. Conclusions: The extended FulVEC cohort confirms durable activity and a reproducible, manageable safety profile in a heavily pretreated population, including CDK4/6i-refractory patients. The exploratory, hypothesis-generating observation of a dose–response gradient between AE severity and clinical outcomes raises the possibility that treatment-emergent AEs may, in some patients, reflect adequate pharmacological exposure to the metronomic regimen. Given confounding by treatment duration and survivor bias, and the absence of pharmacokinetic data, this hypothesis requires prospective validation and does not, at this stage, support any change to current treatment practice. Full article

Background/Objectives: Thymidylate synthase (TYMS) represents an important therapeutic target. Methods: In this study, TYMS expression was analyzed by immunohistochemistry on a tissue microarray containing 17,371 samples from 136 different tumor types. Results: TYMS staining was seen in 42.9% of 15,361 analyzable tumors, with weak staining in 35.4%, moderate in 5.7%, and strong in 1.8%. TYMS occurred in at least one case of 127 categories, of which 71 showed TYMS staining in at least 50% of cases, and 56 included at least one case with strong positivity. TYMS positivity occurred most commonly in lymphomas (81.3–96.5%), sarcomas and sarcomatoid carcinomas (33.3–100%), malignant melanoma (70.5–90.7%), cervical adenocarcinoma (78.3%), and squamous cell carcinomas of various sites (57.1–77.9%). High TYMS expression was linked to advanced pT (p = 0.0097), high grade (p < 0.0001), ER negativity (p < 0.0001), and PR negativity (p = 0.0002) in invasive breast cancer of no special type; high grade (p < 0.0050), high UICC stage (p = 0.0060), and nodal metastasis (p = 0.0120) in clear cell renal cell carcinoma (RCC); high grade (p < 0.05) and nodal metastasis (p = 0.0045) in papillary RCC; high Gleason grade (p < 0.0001) and advanced pT stage (p = 0.0149) in prostatic adenocarcinoma; high pT (p < 0.0001), nodal metastasis (p = 0.005), lymphatic (p = 0.0064) and venous invasion (p = 0.0005), left side location (p < 0.0001), and microsatellite instability (p < 0.0001) in colorectal adenocarcinoma; and high grade (p < 0.0001) in squamous cell carcinomas of different sites. Conclusions: TYMS is often overexpressed across different cancer entities and shows associations with several adverse histopathological parameters commonly used to describe tumor phenotypes. Full article

Background and Objectives: Neoadjuvant dual HER2 blockade combined with chemotherapy is the standard treatment approach for patients with high-risk early-stage or locally advanced HER2-positive breast cancer. However, the optimal chemotherapy backbone and the predictive value of systemic inflammatory biomarkers remain subjects of ongoing investigation. This study aimed to compare pathologic complete response (pCR) rates between neoadjuvant dose-dense doxorubicin/cyclophosphamide followed by paclitaxel plus trastuzumab and pertuzumab (ddAC+THP) and docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP), and to evaluate the predictive performance of pretreatment inflammatory biomarkers. Materials and Methods: In this multicenter retrospective study, patients with HER2-positive breast cancer treated with neoadjuvant ddAC+THP or TCHP between 2019 and 2025 at three tertiary centers were evaluated. Pretreatment inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and hemoglobin, albumin, lymphocyte, and platelet (HALP) score, were calculated from baseline laboratory parameters. Receiver operating characteristic analyses were performed to determine optimal cutoff values, and logistic regression analyses were used to identify predictors of pCR. Results: A total of 197 patients were included, of whom 138 received ddAC+THP and 59 received TCHP. Overall, 125 patients (63.5%) achieved pCR. The pCR rate was numerically higher in the ddAC+THP group than in the TCHP group (65.2% vs. 59.3%), although the difference was not statistically significant (p = 0.431). Among the evaluated biomarkers, SIRI demonstrated the highest discriminatory performance for predicting pCR (AUC: 0.725, 95% CI: 0.652–0.797), followed by NLR (AUC: 0.673, 95% CI: 0.595–0.750). In multivariable analysis, hormone receptor positivity (OR: 0.291, 95% CI: 0.131–0.645; p = 0.002) and elevated SIRI (>0.845) (OR: 0.088, 95% CI: 0.036–0.216; p < 0.001) were independently associated with lower odds of achieving pCR. No significant difference in pCR was observed between treatment regimens across predefined subgroup analyses. Conclusions: Neoadjuvant ddAC+THP and TCHP achieved comparable pCR outcomes in patients with HER2-positive breast cancer. SIRI was independently associated with a lower likelihood of achieving pCR and showed acceptable discriminatory performance. These findings suggest that SIRI may represent an exploratory, readily available inflammatory biomarker for pCR risk stratification; however, prospective validation is required before clinical application. Full article

Geographic variation (GV) in screening patterns for breast cancer exists among Zip Code Tabulation Areas (ZCTAs) in Florida, but most spatial analyses are based on frequentist point estimates which do not formally represent uncertainty. This study used a three-stage analytical approach to the breast cancer screening data at the zip code tract (ZCTA) level in Hillsborough County, Florida (n = 55 ZCTAs): first, a frequentist Poisson regression was applied with diagnostics for multicollinearity; second, global spatial autocorrelation (GSA) analysis was conducted using Moran’s I; and third, a Bayesian Poisson and a Bayesian negative binomial regression were performed, both estimated via the No-U-Turn Sampler in the brms/Stan framework. In ArcGIS Pro 3.6, spatial analyses were carried out. The dependent variable was the number of breast cancer screening exams conducted at the ZCTA level over the study period. Across all racial/ethnic subgroups, the observed number of screenings was correlated with the number of females in the household, while no independent correlation was found for median household income, insurance status or age by stratum variables after adjustment. There was no significant and strong spatial autocorrelation across the study area (Moran’s I = 0.003, z = 0.326, p = 0.745). The Poisson model did best among the Bayesian models with a Bayesian R² of 0.91, RMSE of 5.40, and MBE of 0.02. The results show the usefulness of Bayesian uncertainty quantification in small area public health surveillance and offer a framework for quantifying geographic variation in screening activity in a probabilistic manner. The results only compare screening examination (not population-standardized screening rates) and should be considered to reflect screening volume rather than screening participation. Full article

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype with persistent disparities in stage at diagnosis. While transportation-related exposures are increasingly recognized as environmental health risks, the biological mechanisms linking these exposures to cancer progression remain unclear. This study evaluated whether tumor microRNAs (miRNAs), which regulate gene expression and tumor behavior, mediate the association between transportation burden and TNBC stage at diagnosis. Methods: We analyzed 434 TNBC cases from the Louisiana Tumor Registry (2009–2019). The transportation burden from the 2022 Environmental Justice Index reflects the residential proximity to high-volume roads, railways, and airports. miRNA expression was measured via high-throughput sequencing and normalized using the trimmed mean of M-values method. Three-phase analysis (screening, individual, and multiple mediation) was performed. KEGG pathway enrichment analysis assessed downstream biological pathways. Results: After adjusting for age, race, body mass index, marital status, primary payer, and concentrated disadvantage index (CDI), every 0.10 (10-percentile) increase in transportation burden rank was significantly associated with a 9% increase in the odds of late-stage TNBC diagnosis (Adjusted OR = 1.09, 95% CI: 1.01–1.17, p = 0.021). Five miRNAs significantly mediated this relationship: downregulated hsa-let-7c-5p, hsa-let-7b-5p, hsa-miR-30a-3p, and hsa-miR-92a-3p, and upregulated hsa-miR-151a-3p. Joint mediation analysis demonstrated complete mediation (indirect effect = 0.324; p = 0.027). hsa-let-7c-5p was the primary independent mediator. The enriched pathways included MAPK, PI3K-Akt, Wnt, and p53 signaling. Conclusions: These findings identified molecular pathways linking transportation-related environmental exposures to TNBC progression through dysregulation of miRNAs. By integrating environmental exposure assessment with tumor biology, this study advances our understanding of how the built environment contributes to cancer disparities. Full article

Axillary Lymph Nodes (ALNs) can be affected by breast cancer, and the number of affected ALNs is a determinant factor in breast cancer staging. Microwave imaging (MWI) has emerged as a promising technique for ALN assessment, addressing limitations in conventional imaging modalities. This study investigates, for the first time, the classification of ALNs and axillary regions from microwave signals, without image reconstruction. Classification is performed considering realistic morphological characteristics of ALNs reported in the literature and is based solely on geometric differences, which differ from targets previously explored in microwave-based classification studies. Eighty ALN numerical models were mathematically generated based on state-of-the-art anatomical descriptions. Microwave signals were simulated for three scenarios of different complexity, involving one and two ALNs, representing healthy and metastasised conditions. The methodology evaluated multiple combinations of signal types, feature extraction methods, and classifiers, including scenarios with multiple targets, reflecting clinically relevant axillary conditions and limited angular views inherent to axillary imaging. Classification accuracy reached 95% for single-ALN scenarios using kNN, while more complex two-ALN cases achieved accuracies up to 83.3% using SVM. These results demonstrate the potential of microwave signal-based classification to differentiate healthy and metastasised ALNs and axillary regions, supporting future integration with MWI image interpretation. Full article