Search Results (2,001)

Background: The clinical and oncologic significance of residual microcalcifications after neoadjuvant chemotherapy (NAC) in breast cancer remains poorly defined. While traditionally regarded as radiologic indicators of residual malignancy warranting complete surgical excision, accumulating evidence suggests that many post-treatment calcifications represent benign or in situ changes with limited prognostic relevance. This systematic review synthesizes current evidence to clarify the diagnostic, pathologic, and oncologic implications of persistent calcifications after NAC. Methods: Following PRISMA 2020 guidelines, we conducted a comprehensive search of PubMed, Embase, the Cochrane Library, Scopus, and Google Scholar for studies published between January 2000 and May 2025. Eligible studies included adult breast cancer patients treated with NAC who demonstrated residual calcifications on mammography or MRI with corresponding histopathologic or survival data. Two reviewers independently performed study selection, data extraction, and quality assessment using the Newcastle–Ottawa Scale and AMSTAR-2. Results: Twenty-four studies involving over 3000 patients were included. Across cohorts, 35–55% of residual calcifications were benign, and many others corresponded to ductal carcinoma in situ rather than invasive carcinoma. Calcifications frequently persisted despite pathologic complete response (pCR), particularly in HER2-positive and triple-negative subtypes. MRI demonstrated superior concordance with pathology compared with mammography. Persistent calcifications did not consistently correlate with worse disease-free or overall survival when pCR was achieved. Radiologic–pathologic discordance contributed to overtreatment in some cohorts, including unnecessary mastectomy or extensive resections. Conclusions: Residual calcifications after NAC should not be regarded as a definitive surrogate of residual invasive disease nor as an obligatory indication for complete surgical removal. Their frequent benign or in situ pathology and limited prognostic value support a more individualized approach to surgical planning, prioritizing pathologic response and margin status over radiographic calcifications alone. Full article

Background and Objectives: Contrast-enhanced mammography (CEM) provides both morphological and functional information and may reflect breast cancer biology similarly to Magnetic Resonance Imaging (MRI). Materials and Methods: This single-center retrospective study included 399 women with Breast Imaging Reporting and Data System (BI-RADS) category 0 screening mammograms who subsequently underwent CEM. A total of 76 malignant lesions (68 invasive cancers, 8 ductal carcinoma in situ (DCIS)) with complete imaging and pathology data were analyzed. Invasive cancers were classified into luminal A, luminal B, luminal B/Human Epidermal Growth Factor Receptor 2 (HER2)-positive, HER2-enriched, and triple-negative, and grouped as luminal (Group 1) versus HER2-positive/triple-negative (Group 2). Results: Luminal subtypes predominated (47 of 68, 69%), while 21 of 68 (31%) were HER2-positive or triple-negative. Most cancers appeared as masses with spiculated margins and heterogeneous enhancement. Significant differences were observed in mass shape (p = 0.03) and internal enhancement (p = 0.01). Luminal tumors were more often irregular and spiculated with heterogeneous enhancement, whereas the HER2-positive/triple-negative tumors more frequently appeared round with rim or homogeneous enhancement. Deep learning-derived malignancy scores (iCAD ProFound AI^®) demonstrated good diagnostic performance (area under the curve (AUC) = 0.744, 95% confidence interval (CI) 0.654–0.821, p < 0.001). The median AI score was significantly higher in malignant compared with benign lesions (70% [interquartile range (IQR) 47–93] vs. 38% [IQR 25–61]; Mann–Whitney U test, p < 0.001). Among malignant lesions, iCAD scores varied across molecular subtypes, with higher median values observed in Group 1 versus Group 2 (87% vs. 55%), although the difference was not statistically significant (Mann–Whitney U test, p = 0.35). Conclusions: CEM features mirrored subtype-specific phenotypes previously described with MRI, supporting its role as a practical tool for enhanced tumor characterization. Although certain imaging and AI-derived parameters differed descriptively across subtypes, no statistically significant differences were observed. As deep-learning models continue to evolve, the integration of AI-enhanced CEM into clinical workflows holds strong potential to improve lesion characterization and risk stratification in personalized breast cancer diagnostics. Full article

Although occult breast carcinomas and lesions with uncertain malignant potential are rare, their incidental discovery during symmetrizing mammoplasty can significantly alter the treatment approaches and cancer staging. In the context of oncoplastic surgery, the systematic evaluation of the contralateral breast is a clinical priority that has been underexplored in Eastern Europe. Background/Objectives: This study aimed to assess the incidence and histological characteristics of incidental carcinomas and B 3 lesions detected during contralateral symmetry mammoplasty in patients with breast cancer. Methods: This retrospective study was conducted at the Plastic and Reconstructive Surgery Clinic of the “Pius Brînzeu” County Emergency Clinical Hospital in Timisoara, Romania, over six years (2018–2024), and included 180 of 256 patients who underwent contralateral breast symmetrization. Results: Among the 180 patients, 21 (11.66%) had incidental findings: eight (4.44%) had contralateral carcinomas, and 13 (7.22%) had B3 lesions. The histopathological types identified were invasive ductal carcinoma NST (one case), ductal carcinoma in situ (one case), invasive lobular carcinoma (five cases), and mucinous/papillary carcinoma (one case). Compared to the reported international range of 2–10%, our observed incidence of 11.66% reflects the unique aspects of our patient cohort and the thoroughness of our histological analyses. Conclusions: Detection of contralateral carcinomas and B3 lesions during symmetry mammoplasties underscores the importance of a multidisciplinary approach, comprehensive bilateral screening, and detailed histopathological examination of specimens. Full article

Background/Objectives: Since 1988, the IARC has classified alcohol as a type 1 carcinogen, causally linked to seven types of cancer (oral cavity, pharynx, larynx, esophagus, colorectum, liver and breast carcinomas). Several agencies, such as the WHO and the IARC, hold that there is a direct monotonic association between any gram of alcohol consumed and the risk of cancer, regardless of the drinking pattern. On the other hand, an expanding body of evidence indicates that drinking pattern may substantially modify the effect of alcohol consumption. The Mediterranean alcohol-drinking pattern (MADP) includes different aspects of alcohol consumption, such as preference for red wine, moderate alcohol consumption with meals, spreading consumption over the week and avoiding binge drinking. Conformity to this pattern has shown inverse associations with all-cause mortality, cardiovascular disease and diabetes. However, its relationship with cancer incidence has not been studied yet. Our objective was to assess how alcohol consumption patterns, with particular emphasis on the MADP, relate to the incidence of the seven alcohol-related cancers. This information is needed to support cancer prevention recommendations that may go beyond the amount of alcohol consumed to also include the drinking pattern. Methods: We prospectively followed 19,541 participants in the SUN (“Seguimiento Universidad de Navarra”) cohort for a median of 13.8 years. We classified participants into four groups, namely, abstainers and three further groups according to their adherence to the MADP score (low, moderate and high). Results: A substantial reduction in the risk of alcohol-related cancer incidence was observed only in men for high versus low adherence to the MADP, with an adjusted hazard ratio (HR) of 0.44 (95% confidence intervals (CIs) (0.21–0.92)). The category of moderate adherence to the MADP showed a lower risk of cancer incidence with a tendency towards statistical significance (HR = 0.56, 95% CI, 0.30–1.06). For women, no result reached statistical significance. Conclusions: Based on the available evidence, separate messages by sex should be delivered. In men, the association between alcohol and cancer goes beyond the amount of alcohol consumed, and a Mediterranean drinking pattern may be beneficial even for alcohol-related cancers. Men should, therefore, receive an additional message: among alcohol consumers, greater adherence to the MADP may help lower their risk of developing alcohol-related cancers. No benefit is supported for the MADP against alcohol-related cancers in women. Full article

Sodium regulation is a potentially major driver of cancer metastasis. Voltage-gated sodium channels (VGSCs) and Na,K-ATPase are sodium transporters that are upregulated in many advanced carcinomas and are implicated as metastatic drivers. However, little is known about what drives this overexpression, how these proteins influence metastatic behavior, or whether these complementary sodium transporters are co-regulated in cancer. Using sodium transporter regulation in healthy neurons as a model, the present study demonstrated that the inflammatory mediator tumor necrosis factor alpha (TNFα) affects the expression of VGSCs and Na,K-ATPase in an in vitro model of metastatic breast cancer. Acute TNFα challenge increased RNA for sodium transporter subtypes by 20–100%, TNFα reduced the overall expression of VGSCs by 20–30% at all time-points examined, and long-term administration increased nuclear localization of the α1 subtype of Na,K-ATPase while increasing the overall expression of the α3 subtype. This study established that VGSCs and Na,K-ATPase are co-regulated by TNFα at the RNA level, and it was demonstrated that both TNFα and sodium transport-blocking drugs can significantly impact cellular metastasis-like behavior. Together these data are evidence that inflammation in metastatic breast cancer co-regulates the expression of VGSCs and Na,K-ATPase, and this regulatory system may contribute to carcinogenesis. Full article

Background/Objectives: Research on noble metal nanoparticles (NPs) has increased over the past three decades, with advancements in synthesis techniques refining their physicochemical characteristics, including size, shape, and surface chemistry. Bimetallic NPs (BNPs) offer synergistic properties contributed by both metals. Gold (Au) and palladium (Pd) NPs possess low toxicity, high biocompatibility and loading, ease of synthesis and surface modification. Doxorubicin (DOX) and 5-fluorouracil (5-FU) are potent chemotherapeutic drugs but are rapidly metabolised in the body, producing severe side effects, limiting their use. Hence, innovative strategies to mitigate this is needed. Methods: In this study, AuPd NPs in a core-shell formation were chemically synthesized. The AuPd NPs were conjugated to 5-FU and DOX-encapsulated CS complexes and decorated with the targeting moiety transferrin (Tf). Results: Transmission electron microscopy and nanoparticle tracking analysis confirmed that the BNPs were spherical, with an average size of 73.4 nm. Functionalized BNPs were able to encapsulate more than 70% of 5-FU and DOX, resulting in a controlled drug release profile at pH 4.2. Cytotoxicity levels in human cancer cells, HeLa (cervical carcinoma) and MCF-7 (breast adenocarcinoma), as well as in non-cancer HEK293 (embryonic kidney) cells, revealed that the Tf-targeted nanocomplexes were HeLa cell-specific, with no significant cytotoxicity in the HEK293 cells. Tf-mediated cellular uptake was confirmed by receptor competition studies in the HeLa cells. Apoptosis and oxidative stress analysis confirmed cell death by apoptosis, consistent with the action of 5-FU and DOX. Conclusions: This study highlighted the potential of this BNP-nanocomplex as a suitable vehicle for drug delivery. Full article

The gut microbiome has emerged as a key regulator of human health, influencing not only metabolism and immunity but also the development and treatment of cancer. Mounting evidence suggests that microbial dysbiosis contributes to oncogenesis by driving chronic inflammation, producing genotoxic metabolites, altering bile acid metabolism, and disrupting epithelial barrier integrity. At the same time, the gut microbiome significantly modulates the host response to oncotherapies including chemotherapy, radiotherapy, and especially immunotherapy, where microbial diversity and specific taxa determine treatment efficacy and toxicity. This review synthesizes current evidence on the role of the gut microbiome in both oncogenesis and oncotherapies, focusing on thirteen cancers with the strongest and most clinically relevant microbiome associations, colorectal cancer, gastric cancer, hepatocellular carcinoma, gallbladder cancer, esophageal cancer, pancreatic cancer, oral squamous cell carcinoma, cervical cancer, prostate cancer, breast cancer, lung cancer, brain cancer, and melanoma. These cancers were selected based on robust mechanistic data linking microbial alterations to tumor initiation, progression, and therapy modulation, as well as their global health burden and translational potential. In addition, we have provided mechanistic insights or clinical correlations between the microbiome and cancer outcomes. Across cancers, common microbial mechanisms included pro-inflammatory signaling (e.g., NF-κB and STAT3 pathways), DNA damage from bacterial toxins (e.g., colibactin, nitrosating species), and metabolite-driven tumor promotion (e.g., secondary bile acids, trimethylamine N-oxide). Conversely, beneficial commensals such as Faecalibacterium prausnitzii and Akkermansia muciniphila supported antitumor immunity and improved responses to immune checkpoint inhibitors. In conclusion, the gut microbiome functions as both a driver of malignancy and a modifiable determinant of therapeutic success. Integrating microbiome profiling and modulation strategies such as dietary interventions, probiotics, and fecal microbiota transplantation into oncology practice may pave the way for personalized and more effective cancer care. Full article

Background/Objectives: Breast cancer remains one of the leading causes of cancer-related mortality. Still, limited drug delivery systems for genistein, a powerful natural anticancer agent, draw significant attention. We aimed to develop a co-therapeutic/synergistic dual-compartment system; genistein-loaded pumpkisome nanovesicles (GNS-PKs) incorporated into pullulan microneedle patches (MNs), and to explore its anticancer activity. Methods: GNS-PKs were prepared and characterized for particle size (P.S), polydispersity (PDI), zeta potential (Z.P), encapsulation efficiency (E.E%), and stability. Afterward, they were embedded in pullulan-dissolving microneedle arrays and characterized for release kinetics, mechanical strength, and in vitro cytotoxicity. The in vivo efficacy was evaluated in mice with solid Ehrlich Ascites Carcinoma (EAC), focusing on tumor volume, oxidative stress, inflammatory cytokines, Epidermal Growth Factor (EGFR) expression biomarkers, and histopathological analysis. Results: The optimized nanovesicles had a particle size of 170 nm, a zeta potential of −42 mV, and an entrapment efficiency of up to 92%. Pullulan microneedles demonstrated significantly high mechanical strength and effective deep penetration. In addition to, it markedly decreased MCF-7 cellular viability (IC₅₀ = 3.5 µg/mL). Besides, it had a 76% reduction in tumor volume, significantly increased the antioxidant activity (SOD, CAT, GSH), decreased the levels of inflammatory biomarkers (IL-6, COX-2, NF-κB), and markedly downregulated the EGFR expression (p < 0.0001). Histological study revealed decreased mitotic activity and large tumor cells, with minimal systemic damage. Conclusions: GNS-PKs-pullulan microneedle system offers a hope for an innovative, potent, effective, and non-invasive strategy for breast cancer treatment with high antitumor efficacy. Full article

Background/Objectives: High-risk (B3) breast lesions are a heterogeneous group with uncertain malignant potential. Methods: We systematically reviewed and meta-analyzed the ability of artificial-intelligence (AI) models to predict malignant upgrades (a ductal carcinoma in situ or an invasive carcinoma) after biopsy. A comprehensive search of medical and engineering databases through 27 July 2025 identified retrospective studies that developed or validated AI models for upgrade prediction in cohorts with ≥20 B3 lesions and confirmed outcomes at surgical excision or after ≥24 months of follow-up. Results: Three single-center studies (557 lesions, 91 upgrades) met the eligibility criteria. Pooled analysis focused on clinically meaningful operating points rather than raw accuracy metrics. Models tuned for high sensitivity achieved high negative predictive values (pooled 0.95), suggesting reliable identification of lesions suitable for surveillance, but positive predictive values were modest and heterogenous (0.15–1.00), reflecting trade-offs between avoiding missed upgrades and reducing unnecessary excisions. Only two studies reported area-under-the-receiver-operating-characteristic curves, which pooled to 0.72, indicating moderate discrimination. Conclusions: Although limited by small sample sizes and single-center designs, these findings suggest that AI could aid decision-making for B3 lesion management. Prospective multicenter validation and standardized reporting are needed to evaluate clinical utility. Full article

Background and Clinical Significance: Metastatic breast cancer is a major global health burden, with common metastatic sites including the bones, lungs, liver, and brain. Cardiac metastasis is rare and often clinically silent, leading to underdiagnosis. Recognizing cardiac involvement, even when asymptomatic, is important for understanding the full extent of disease and ensuring optimal patient care. Case Presentation: We report the case of a woman with advanced breast carcinoma who showed no clinical or imaging evidence of cardiac involvement throughout the course of her illness. Following her death from progressive metastatic disease, an autopsy revealed metastatic carcinoma infiltrating the myocardium and epicardium without gross cardiac abnormalities. Histological and immunohistochemical analysis confirmed the tumor’s origin from breast carcinoma. Conclusions: This case illustrates the potential for clinically occult cardiac metastasis in breast cancer and underscores the importance of pathological examination in detecting hidden metastatic sites. The absence of cardiac symptoms or imaging abnormalities highlights the diagnostic challenge of this rare manifestation and the need for greater awareness in managing advanced malignancies. Full article

Background: Breast cancer is the most prevalent cancer in women, and metastatic breast cancer remains a major cause of cancer-related deaths. Resveratrol (RSV) is a natural compound found in various plants and is known to exhibit various anti-cancer effects. The present study aims to investigate the therapeutic effects and mechanisms of RSV in inhibiting breast cancer metastasis in a murine model of 4T1 breast tumor that shares close molecular features with human triple negative breast cancer. Methods: Murine breast cancer 4T1 cells were used to examine the effects of RSV on breast cancer metastasis and epithelial–mesenchymal transition (EMT). In vitro cell proliferation and Transwell migration assays and in vivo 4T1 tumor transplantation models were established in female Balb/c mice to determine the anti-metastatic effects of RSV and its mechanism of action. Results: RSV significantly inhibited 4T1 tumor cell migration and significantly decreased expression levels of EMT markers Snail and Vimentin, as well as the nuclear translocation of β-catenin both in vitro and in vivo. Knockdown of β-catenin similarly reduced the expression levels of EMT markers. RSV significantly decreased the number of lung metastases in 4T1-implanted mice by inhibiting Wnt/β-catenin signaling pathway activation. RSV (150 mg/kg/day) reduced the number of visible tumor metastatic nodules and the histological count of metastatic lung carcinomas by 51.82% and 62.58%, respectively, compared to vehicle administration. Conclusions: Our study provides important new mechanistic insight into the strong anti-cancer effects of RSV in inhibiting 4T1 breast cancer metastasis by preventing Wnt/β-catenin signaling pathway-mediated epithelial–mesenchymal transition. These findings suggest the therapeutic potential of RSV as a promising drug in the treatment of metastatic breast cancer. Full article

Transarterial radioembolization (TARE) is an established therapy for primary and secondary hepatic malignancies. Outcomes depend heavily on dosimetry, which has evolved from empirical and body-surface-area methods to partition and voxel-based approaches. This review summarizes current evidence for advanced (personalized) dosimetry across tumor types, highlights emerging dose–response concepts, and outlines practical barriers and implementation strategies. A narrative review of peer-reviewed clinical studies and trials evaluating dosimetry in TARE, with emphasis on hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), metastatic colorectal cancer (mCRC), neuroendocrine tumor (NET), and breast cancer liver metastases, was performed with comparison of single-compartment medical internal radiation dosimetry method (MIRD), partition (multicompartment) methods, and voxel-based dosimetry methodologies. Personalized dosimetry improves outcomes in multiple tumor types. A randomized trial in HCC showed superior overall survival with partition-based dosing versus MIRD. In selective HCC treatments, voxel-derived metrics (e.g., D95) correlate with complete pathologic necrosis, suggesting benefit beyond mean dose targets. For iCCA, data associate higher tumor doses with better radiologic response, progression-free survival, and downstaging. In mCRC, voxel-based and threshold analyses link specific tumor and margin doses with metabolic/radiographic response and survival. Smaller series in NET and breast cancer indicate dose–response relationships using advanced dosimetry. Evidence supports broader adoption of advanced dosimetry in TARE. Emerging strategies that ensure adequate coverage of the “coldest” tumor regions and thoughtful particle-load planning may further optimize results. Standardized protocols, prospective validation, and scalable workflows are needed to accelerate implementation. Full article

Background/Objectives: β-Lapachone and triapine are compounds with recognized antitumor potential—the former is an ortho-naphthoquinone, and the latter a thiosemicarbazone inhibitor of ribonucleotide reductase. This study aimed to synthesize and evaluate new β-lapachone-based thiosemicarbazones (TSC1–TSC6) as potential antineoplastic agents. Methods: Lapachol was isolated from Tabebuia sp. and used to obtain ortho-naphthoquinones (2–4), which served as precursors for thiosemicarbazones (TSC1–TSC6). NMR and HRMS spectra were used to characterize the compounds. Their cytotoxic activity was evaluated in vitro against murine melanoma (B16–F10), colon carcinoma (CT26.WT), and breast cancer (4T1) cell lines, as well as normal fibroblasts (L929). Pharmacokinetic parameters were predicted in silico using ADMETLab 3.0. Results: β-Lapachone exhibited strong cytotoxicity toward tumor cells with moderate effects on normal cells, while thiosemicarbazones of β-lapachone, TSC1, and TSC3 demonstrated lower potency but greater selectivity. The β-lapachone-3-sulfonic acid showed high activity against melanoma and breast cancer cells and low toxicity toward normal cells, indicating tumor selectivity. In contrast, their thiosemicarbazones, TSC2, TSC4, and TSC6, showed weak or no antiproliferative activity. The 3-iodo-β-lapachone was cytotoxic to both tumor and normal cells, whereas its derivative TSC5 demonstrated moderate activity with reduced toxicity. β-Lapachone, β-lapachone-3-sulfonic acid, TSC1, and TSC3 exhibited favorable ADME profiles (QED ≈ 0.61–0.66), suggesting good oral bioavailability. Conclusions: The β-lapachone-3-sulfonic acid and the β-lapachone-based thiosemicarbazones TSC1 and TSC3 emerged as promising lead candidates, combining tumor selectivity, favorable pharmacokinetic properties, and structural innovation for the development of safer and more effective antineoplastic agents. Full article

Objectives: Primary objective was to report the feasibility, safety and efficacy of percutaneous ablation of hepatic malignant tumors that are undetectable or inconspicuous in non-enhanced computed tomography (CT) scans using an electromagnetic navigation system with a marker option. Secondary objectives included the evaluation of technical parameters including the accuracy of needle placement, the number of control CT acquisitions, and procedural duration. Methods: This prospective study (performed from 1 March 2022 until 30 November 2024) included all patients with hepatic tumors (not visible or poorly defined on non-enhanced CT) who underwent percutaneous microwave ablation (MWA). Technical efficacy was assessed with contrast-enhanced CT immediately post-ablation, and oncologic outcomes (overall and progression-free survival) were evaluated with MRI at 1, 3, and 6 months. Results: Fifteen patients (12 males, 3 females; mean age of 66 years) with 16 tumors (median diameter of 15 mm) were treated in 16 sessions. Tumor types included hepatocellular carcinoma (n = 7), colorectal metastasis (n = 4), ocular melanoma (n = 1), neuroendocrine tumor (n = 1), intrahepatic cholangiocarcinoma (n = 1), and breast cancer metastasis (n = 1). Median procedure time was 53 min, scans number was nine, needle length was 12 cm, and median deviation was 1 mm. No complications were reported. Primary efficacy rate was 94% (15/16), rising to a secondary (assisted) technique efficacy of 100% after re-ablation (one session). During median follow-up of 23 months, local tumor progression-free survival was 100%; distant progression-free survival was 80%, and two patients (13.3%) died, one being cancer-related. Conclusions: Electromagnetic navigation with a marker option enables safe, accurate, and effective MWA of inconspicuous hepatic tumors, achieving excellent local control with favorable oncologic outcomes. Full article

Background/Objectives: The polypeptide N-acetylgalactosaminyltransferase (GALNT) family initiates mucin-type O-glycosylation, a post-translational modification that plays a pivotal role in cellular signaling, adhesion, and immune evasion. Dysregulated GALNT expression has been increasingly implicated in carcinogenesis. Methods: We reviewed the literature on the expression, function, and clinical relevance of GALNT isoforms across various cancers, with a focus on their mechanistic roles, biomarker potential, and therapeutic implications. Results: Aberrant GALNT expression is observed in numerous malignancies, including breast, colorectal, gastric, lung, ovarian, and hepatocellular carcinomas. Isoforms such as GALNT1, -T2, -T3, and -T14 contribute to tumorigenesis by modulating the glycosylation of mucins such as Mucin-1 (MUC1), epithelial growth factor receptors (EGFR), and other signaling proteins. These alterations promote cancer cell proliferation, metastasis, epithelial–mesenchymal transition (EMT), and chemoresistance. Deranged GALNT expression is frequently associated with poor prognosis, and certain GALNT genotypes predict treatment response. However, functional redundancy among isoforms poses challenges for selective targeting. Conclusions: Despite their strong potential as modulators of cancer progression, GALNTs face substantial limitations in terms of substrate identification, mechanistic clarity, immune relevance, and therapeutic tractability. Overcoming these challenges requires advanced glycoproteomics, development of isoform-specific tools, and integrated studies across cancer and immunology to fully harness GALNT biology for clinical benefit. Full article