Search Results (85)

Total laryngectomy (TL) is still the standard treatment for advanced laryngeal and hypopharyngeal cancer, with pharyngeal reconstruction being a challenging determinant of outcomes. We searched PubMed/MEDLINE, Scopus, and Web of Science from inception to July 2026 for studies reporting pharyngeal reconstruction techniques or fistula outcomes after TL. This narrative review synthesizes current evidence on reconstruction following TL across three domains: prevention, reconstruction, and management of pharyngocutaneous fistula (PCF). Defect classification into minimal, partial, and circumferential categories guides reconstructive decision-making, each supported by a distinct evidence stream. Risk stratification identifies prior radiotherapy, poor nutritional status, sarcopenia, and salvage setting as the strongest PCF predictors. For minimal defects, stapler-assisted closure reduces PCF risk in primary TL, and double-layer manual closure outperforms single-layer repair. Partial defects in the salvage setting benefit from vascularized tissue augmentation, with pedicled onlay flaps associated with lower fistula rates than primary closure or free flap patching. For circumferential defects, network meta-analytic data suggest that the free jejunal flap ranks highest for fistula prevention. Comparative cohort data indicate that anterolateral thigh flaps may offer better long-term speech outcomes. The optimal choice depends on the outcome prioritized. Salivary bypass tubes represent the most consistently supported adjunct for fistula and stenosis prevention. PCF management follows a stage-based approach: conservative care for early fistulas, negative pressure wound therapy as a bridge in subacute cases, and vascularized flap reconstruction for chronic or refractory fistulas. Full article

Background/Objectives: Supraglottic and hypopharyngeal carcinomas are aggressive malignancies that are often diagnosed at advanced stages. Timely recognition of these malignancies is influenced by many factors, such as endoscope quality and experience. This study evaluated the potential of artificial intelligence (AI) to support real-time detection and classification of such lesions during flexible endoscopy in the outpatient clinic. Methods: A previously developed deep learning (DL) algorithm was extended from a glottic lesion model to the unified localization and classification of glottic, supraglottic, and hypopharyngeal lesions during flexible endoscopy. Lesion frames were extracted from endoscopy videos obtained at two head and neck oncology centers and one secondary referral center between 2012 and 2024. These frames were annotated and labeled based on histopathological or clinically confirmed reference diagnoses. The primary outcome was the unified model’s performance in detection of lesions per frame. After training (70% of data), the positive predictive value (precision) and sensitivity (recall) of this model were calculated on an independent test set (30% of data), stratified by subsite and tumor (T-) classification. Secondly, the model’s binary classification performance (benign or malignant) was evaluated. Results: From 490 supraglottic and hypopharyngeal endoscopy videos, 40,059 frames with a benign or malignant lesion were extracted and added to the 56,036 glottic lesion frames in the database, comprising 1336 lesion videos and 123 healthy control videos (total n = 1459). On the test set, the model achieved a detection precision of 92.1% (95% CI: 90.9–93.2) and a recall of 73.3% (95% CI: 69.8–76.6). Detection performance increased with higher T-stage. Among correctly detected lesion instances in a malignancy-dominated test set (65.3% of lesion instances), sensitivity for malignancy detection was 94.3% (95% CI: 91.8–96.5). Combined end-to-end performance for correct malignant lesion detection and classification was estimated at 69.1% (object-level recall 73.3% × classification sensitivity 94.3%). Evaluation of 33 lesion-free videos demonstrated a mean frame-level specificity of 46.6% and a median of 19 false positive detections per video. Conclusions: This is the first study to report a DL model for real-time endoscopic detection and classification of benign and malignant laryngeal and pharyngeal lesions. The developed model showed promising lesion detection and cancer classification performance in the evaluated test set. T1 tumor detection remains an important limitation, particularly because early-stage detection is a primary aim of AI-assisted endoscopy. Further model testing is required in real-world lesion prevalence settings, where external validation and clinical usability should be investigated. Full article

Background/Objectives: Head and neck cancer survivors experience many late toxicities following radiation therapy. This study aims to identify symptom clusters of late toxicities and their related factors in head and neck cancer survivors. Methods: A cross-sectional study was conducted with 83 survivors (pharyngeal or laryngeal cancer) who had received radiation therapy at least one year earlier. Nine late toxicities were assessed using the Japanese version of the Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) and a custom questionnaire. Quality of life (QoL) and related factors were evaluated with the European Organization for Research and Treatment of Cancer (EORTC QLQ-C 30), Hospital Anxiety and Depression Scale (HADS), UCLA Loneliness Scale, and Liebowitz Social Anxiety Scale (LSAS). Exploratory factor analyses and multiple regression analyses were performed. Results: All participants reported at least one symptom. Dry mouth (90.4%) and difficulty swallowing (72.3%) were particularly prevalent. Exploratory factor analysis (EFA) identified two symptom clusters (SCs): an oropharyngeal dysfunction cluster (pain, trismus, taste changes, difficulty swallowing, hoarseness) and a dry mouth cluster (dry mouth, sticky saliva). Regression analysis indicated that higher scores in both clusters were significantly associated with lower global QoL (oropharyngeal dysfunction SC: β = −0.427, p < 0.001; dry mouth SC: β = −0.268, p = 0.009). Chemoradiotherapy (CRT) was also significantly associated with higher cluster scores (oropharyngeal dysfunction SC: β = 0.233, p = 0.020; dry mouth SC: β = 0.343, p = 0.001). Conclusions: Late toxicities following radiation therapy include two clusters: oropharyngeal dysfunction cluster and dry mouth cluster. Head and neck cancer survivors with higher SC scores had lower global QoL scores and had undergone CRT. These findings may aid in the assessment and self-management support of head and neck cancer survivors after radiation therapy. Full article

Background/Objectives: The severity of radiation-induced toxicity in head and neck cancer (HNC) radiotherapy should be predicted for the prognosis of the patient’s quality of life. Multiple organs at risk (OARs) are susceptible to toxicity in the head and neck. Hence, we aimed to investigate the feasibility of evaluating radiation-induced xerostomia and dysphagia based on multi-OAR dosiomics in HNC radiotherapy. Methods: We used radiotherapy treatment planning and toxicity data collected from 44 patients with HNC. High- and low-toxicity grades were classified using dosiomic models derived from multiple OARs. Dosiomic features were computed from the planned dose distribution per OAR. A prediction model was derived using selected dosiomic features and toxicity grades based on extreme gradient boosting for every OAR and all OARs. The model performance was evaluated in terms of the area under the curve (AUC) from leave-one-out cross-validation. Models based on dose volume histogram features and combining these with dosiomic features were derived to compare the prediction performance per OAR. Performance comparisons across OARs were also conducted. Results: The prediction models with the highest AUCs for xerostomia and dysphagia were the dosiomic model using all OARs, with an AUC of 0.843 (95% confidence interval—CI, 0.725–0.961), and that using the middle pharyngeal constrictor muscle, with an AUC of 0.878 (95% CI, 0.772–0.984). Conclusions: The evaluation results demonstrated the feasibility and potential of predicting radiation-induced toxicities based on multi-OAR dosiomics in HNC radiotherapy. Further investigations are required to determine the generalizability of our findings. Full article

Isodonis Excisoidis Herba (IEH) is a newly discovered herbal medicine used to treat esophageal cancer, chronic pharyngitis, and hepatitis, and ent-kaurane diterpenoids are its main active components. However, systematic studies on the chemical profile of ent-kaurane diterpenoids are lacking. In this study, UHPLC-LTQ-Orbitrap-MS was performed to investigate the fragmentation behaviors of three different types of ent-kaurane diterpenoids from IEH. Bridgehead-unsubstituted 7,20-epoxy-ent-kaurane diterpenoids yielded ions with typical losses of R₇H, R₁H, R₁₄H, CH₂O, CO, and R₆H. The [M + NH₄ − NH₃ − R₂₀]⁺ precursor ions at 331.1895 and the characteristic ions at m/z 313.1792, 295.1686, 285.1842, 277.1581, 267.1737, and 249.1632 were the most possible fragmentation pathways for bridgehead-substituted 7,20-epoxy-ent-kaurane diterpenoids. Fragmentation with the successive loss of multiple 18, 42, or 60 Da occurring in the OH groups and OAc groups is characteristic of 7,20-non-epoxy-kaurane diterpenoids. Using accurate mass measurements for each precursor ion and the subsequent fragmented ions, a total of 94 ent-kaurane diterpenoids were identified or tentatively characterized in IEH, including 48 potentially new ent-kaurane diterpenoids. Full article

Objectives: Among people with HIV (PWH), the epidemiology of malignant tumors has shifted from AIDS-defining malignancies (ADMs) to non-AIDS-defining malignancies (NADMs). This study examined temporal changes in the standardized incidence ratio (SIR) of malignant tumors in an HIV cohort in Japan. Methods: A retrospective cohort study was conducted of 3793 men treated for HIV at Osaka National Hospital between 2007 and 2024. Diagnoses of malignant tumors were identified from medical records and the expected numbers of cases were calculated using cancer incidence rates for the general male population of Japan. SIRs and 95% confidence intervals (CIs) were calculated and temporal changes across four periods (2007–2011, 2012–2016, 2017–2020, and 2021–2024) were evaluated using the p for trend. Results: The overall SIR for malignant tumors decreased from 5.12 (95% CI: 4.02–6.43) in 2007–2011 to 0.86 (95% CI: 0.64–1.14) in 2021–2024, mainly owing to a decline in ADMs (SIR: 111.93 to 5.70), including Kaposi’s sarcoma (SIR: 4269.39 to 547.26) and AIDS-related lymphoma (SIR: 62.18 to 3.13). The overall SIR for NADMs was similar to that of the general population (1.04; 95% CI: 0.89–1.22), and decreased from 1.64 to 0.69, but the risks of anal cancer (SIR 40.63) and oral/pharyngeal cancer (SIR 3.16) remained high. Conclusions: Among men with HIV in Japan, the overall risk of ADMs and NADMs has decreased; however, the risk of specific NADMs remains high. Cancer prevention strategies for PWH need to focus on high-risk NADMs. Full article

Background: Human papillomavirus (HPV) is the leading cause of sexually transmitted infections (STIs). It is found in extragenital regions, including the oropharyngeal cavity. Its presence in this area is linked to the increased prevalence of oral and pharyngeal cancer cases in young individuals, which is associated with current sexual practices in the young population. Objective, the objective of this study was to estimate the prevalence of HPV infection in the oropharyngeal cavity and identify associated factors within the student community of the Engineering and Chemical Sciences Unit of the University of Veracruz. Methods: an observational, descriptive, and transversal study was conducted. The study included 136 sexually active students aged 18 to 25 without oropharyngeal infection. After obtaining informed consent from all participants, mouthwashes were collected from the oropharyngeal cavity for subsequent detection of viral DNA and HPV genotyping using the PCR-RFLP technique. Risk factors were further assessed through a private questionnaire. For statistical analysis, a bivariate analysis of the main risk factors was performed, and Odds Ratios (OR) and 95% Confidence Intervals (CI) were calculated. Results: The results showed that HPV was detected in 6 participants, resulting in a prevalence of 4.4% (95% CI, 0.92–7.91), with genotypes 11, 52 and 58 identified. Notably, participants with a sexual orientation other than heterosexual had a 7.5-fold higher association with HPV. Conclusions: these findings indicate that low- and high-risk HPV infection in the oropharyngeal cavity is associated with risky sexual behavior in young individuals. Therefore, understanding the specifics of sexual activities is necessary to better comprehend viral transmission and spread among HPV-positive students. Full article

Background and Objectives: Oropharyngeal squamous cell carcinoma (OPSCC) is a common type of head and neck cancer with a progressive incidence in recent years. The limitations and the side effects associated with the current treatments require new therapeutic alternatives. Silibinin (SIL) is a phytocompound with multifaceted properties that has demonstrated antitumor effects in several types of cancer. The aim of this study was to assess the potential anticancer effects of SIL in Detroit 562 human pharyngeal cancer cells, an ideal model for HPV-negative OPSCC. Materials and Methods: Detroit 562 cells and HGF-1- human gingival fibroblasts were used as experimental models. For the mechanistic investigations, different methods, such as MTT assay, bright field microscopy, immunofluorescence staining, and specific assays and kits were applied to quantify intracellular ROS production, activation of caspases, and the colony formation assay. Results: Treatment with SIL (25–200 µM) for 48 h induced a selective cytotoxic effect in Detroit 562 cancer cells, being minimally toxic to healthy cells. The cytotoxic mechanism of action was characterized by a decreased cell viability, morphological alterations, elevation of intracellular ROS, decreased mitochondrial potential, mitochondrial and nuclear dysmorphologies, activation of caspases 9 and 3/7 and apoptosis occurrence, and decreased long-term colony formation. Conclusions: These findings show that SIL could represent a potential alternative therapy for HPV-negative OPSCC by triggering mitochondrial apoptosis and exerting a decline in the colonogenicity of Detroit 562 cancer cells. Full article

Background/Objectives: The association between gastroesophageal reflux disease (GERD) and extraesophageal malignancies remains unclear. This study aimed to systematically evaluate the relationship between GERD and these cancers. Methods: PubMed, Embase, Scopus, Cochrane Library, and Web of Science were searched for studies reporting risk estimates—risk ratios (RRs), odds ratios (ORs), hazard ratios (HRs), or standardized incidence ratios (SIRs)—of GERD and extraesophageal malignancies. Mendelian randomization (MR) studies with available risk estimates and 95% confidence intervals (CIs) were also included. Pooled estimates with 95% CIs were calculated using a random-effects model. Results: As of 21 May 2025, a total of 37 studies were included in the analysis. GERD was significantly associated with an increased risk of several extraesophageal malignancies, including pharyngeal cancer (pooled RR = 2.04; 95% CI: 1.38–3.02), with a particularly high risk observed for hypopharyngeal cancer (RR = 2.95; 95% CI: 1.99–4.37; I² = 60.24%). Elevated risks were also identified for laryngeal cancer (RR = 2.23; 95% CI: 1.41–3.52) and lung cancer (RR = 1.20; 95% CI: 1.01–1.42). No significant association was found between GERD and colorectal cancer (RR = 1.19; 95% CI: 0.68–2.09), and findings regarding oral cancer were inconsistent across studies. Six MR studies confirmed a positive causal relationship between GERD and lung cancer, while one MR study suggested a potential causal association with oral cancer and another with pancreatic cancer. Conclusions: Our findings suggest that GERD may be a significant risk factor for pharyngeal, laryngeal and lung cancers. Appropriate evaluation and surveillance in patients with GERD may be warranted. Full article

Background: ADAR1 (ADAR), ADAR2 (ADARB1), and ADAR3 (ADARB2) are deaminase adenosine RNA-specific enzymes that play a significant role in RNA metabolism. ADAR1 (ADAR) and ADAR2 (ADARB1) catalyze A-to-I editing and ADAR3 (ADARB2) plays a regulatory role. The role of these three genes still remains unknown in head and neck cancers (HNSCC). The aim of this study is to reveal the role of deaminase adenosine RNA-specific enzymes in pathomechanisms of HNSCC and to investigate their potential utility as diagnostic and/or prognostic biomarkers. Methods: The quantitative PCR analysis was conducted using RNA isolated from 22 pairs of matched tumor and adjacent normal tissues, 76 formalin-fixed paraffin-embedded (FFPE) tumor samples, and a panel of HNSCC cell lines (DOK, SCC-25, SCC-40, FaDu, and CAL-27). In parallel, transcriptomic and clinical data from the Cancer Genome Atlas HNSCC cohort were analyzed. Patients were stratified into high- and low-expression groups, and statistical assessments included overall survival and progression-free interval analyses, evaluation of gene expression in relation to clinicopathological parameters, correlation with other genes, and functional pathway exploration using gene set enrichment analysis. Results: ADARB2 was significantly downregulated in HNSCC tumor tissues compared to adjacent normal mucosa (p = 0.044), with discriminatory potential to distinguish malignant from non-malignant tissues (AUC = 0.692, p = 0.029). TCGA data confirmed ADAR (p < 0.0001) and ADARB1 (p < 0.0001) upregulation in tumors, while ADARB2 was markedly reduced (p = 0.04). Patients with high ADARB2 expression showed significantly longer overall survival (pa = 0.0121; pb = 0.0098), with a trend toward improved progression-free survival (pb = 0.0681). Subsite analysis revealed high ADAR expression correlated with poor OS in pharyngeal tumors (p < 0.05), whereas high ADARB2 expression was linked to improved DFS (pa = 0.0023, pb = 0.0047). GSEA indicated that low ADARB2 expression was enriched in oncogenic pathways, including Wnt/β-catenin (p = 0.006), MYC targets (p = 0.009), and TGF-β1 (p = 0.009). Conclusions: ADARB2 expression was significantly reduced in HNSCC tumor tissues compared to normal mucosa and demonstrated strong discriminatory power for distinguishing malignant from non-malignant samples. High ADARB2 expression was associated with markedly improved overall survival, whereas low expression correlated with enrichment of oncogenic pathways, including Wnt/β-catenin, Notch, and Hedgehog, consistent with a poorer clinical prognosis. These findings highlight ADARB2 as a promising diagnostic biomarker and independent prognostic factor in HNSCC. Full article

Background/Objectives: The implementation of adaptive radiation therapy (ART) is increasingly becoming widely available in the clinical practice of radiotherapy (RT). For patients with pharyngeal cancer receiving RT, this study aimed to develop a deep learning (DL) model by merging baseline and ART simulation computed tomography (CT) images to predict treatment outcomes. Methods: Clinical and imaging data from 162 patients of newly diagnosed oropharyngeal or hypopharyngeal cancer were analyzed. All completed definitive treatment and their baseline and ART non-contrast simulation CTs were utilized for training. After augmentation of the CT images, a deep contrastive learning model was employed to predict the occurrence of local recurrence (LR), neck lymph node relapse (NR), and distant metastases (DM). Receiver operating characteristic curve analysis was conducted to evaluate the model’s performance. Results: Over a median follow-up period of 34 months, 53 (32.7%), 36 (22.2%), and 23 (14.0%) patients developed LR, NR, and DM, respectively. Following the integration of prediction results from baseline and ART simulation CTs, the area under the curve for predicting the occurrence of LR, NR, and DM reached 0.773, 0.747, and 0.793. At the same time, the accuracy for the three endpoints was 72.4%, 74.7%, and 75.7%, respectively. Conclusions: For patients with pharyngeal cancer ready to receive RT-based treatment, our proposed models can predict the development of LR, NR, or DM through baseline and ART simulation CTs. External validation needs to be conducted to confirm the model’s performance. Full article

Medullary thyroid carcinoma (MTC) is a thyroid tumor with neuroendocrine properties purportedly derived from C-cells. The biochemical activity of medullary thyroid carcinoma includes the production of calcitonin and carcinoembryonic antigen, which are sensitive tumor markers, facilitating diagnosis, follow-up, and prognostication. Calcitonin-negative medullary thyroid carcinoma is a rare, poorly understood primary neuroendocrine carcinoma of the thyroid characterized by classic medullary thyroid carcinoma morphology without raised serum calcitonin and with or without the expression of calcitonin detected by immunohistochemistry. Previous studies reported that C-cells were derived from the neural crest; however, more recently, C-cells have been indisputably shown to be derived from the pharyngeal endoderm and ultimobranchial bodies. Ultimobranchial body (UBB) remnants can persist in the thyroid and express p63, but their function is poorly understood. Some have postulated that ultimobranchial bodies may be the “stem” cell of the thyroid and may be precursors for thyroid tumors, particularly mixed tumors with follicular and medullary components. We present a unique case of calcitonin-negative MTC in a 58-year-old male arising in an inflamed and fibrotic thyroid with numerous scattered ultimobranchial body remnants and concomitant C-cell hyperplasia/medullary microcarcinoma (CCH/MMC). The ultimobranchial body remnants, C-cell hyperplasia, and medullary thyroid carcinoma were MTC classifier positive according to ThyroSeq^®. The areas representing CCH/MMC expressed calcitonin by IHC while the main MTC tumor was negative. An additional unique feature was an area demonstrating a “mixed” C-cell/thyroid follicular epithelial phenotype. In this review we review the possible etiologies of calcitonin-negative MTC, the possibility of a neoplastic sequential progression from ultimobranchial bodies to CCH/MMC to medullary thyroid carcinoma with the individual elements (UBB, CCH/MMC, MTC) demonstrated in this thyroid, and previous postulations that ultimobranchial bodies may be the source of some follicular thyroid cancers, medullary thyroid cancers, and mixed tumors of medullary and follicular epithelial types. Full article

Background: Head and neck cancers (HNCs) represent a substantial global health burden, with an estimated mortality rate exceeding 50% annually. Among the various subsites, pharyngeal and laryngeal carcinomas are recognized as two of the most aggressive and challenging forms, characterized by high incidence, poor prognosis, and a strong association with advanced-stage diagnosis. Methods: A systematic literature review was performed using electronic literature databases (e.g., PubMed, Google Scholar). Search terms included “head and neck cancer”, “laryngeal cancer”, and “pharyngeal cancer”. Selected studies are published within the last two decades. Results: Laryngeal cancer constitutes approximately 40% of head and neck malignancies, with a clear male predominance, and pharyngeal cancer shows increased incidence in male populations from the Americas and Africa. Despite therapeutic advancements in radiotherapy, chemotherapy, and immunotherapy, overall survival rates remain unsatisfactory. Moreover, patients are at increased risk for second primary malignancies, particularly within the lungs and esophagus, due to the widespread carcinogenic exposure along the aerodigestive tract. Conclusions: To mitigate the morbidity and mortality associated with pharyngeal and laryngeal cancers, early detection, risk factor mitigation, and public health education are imperative. Enhancing screening among high-risk populations and adopting personalized, multidisciplinary treatment strategies may significantly improve clinical outcomes and long-term survival. Full article

Late radiation-associated dysphagia (late-RAD) remains a challenge in head and neck cancer (HNC) survivorship, despite advancements in treatment methods. Although Fiberoptic Endoscopic Evaluation of Swallowing (FEES) stands as the preferred diagnostic approach for oropharyngeal dysphagia assessment in the HNC population, current studies lack a FEES-derived swallowing parameter characterization and phenotypic classification within this specific cohort. This study sought to employ FEES-based assessment to characterize swallowing safety and efficacy profiles, identify distinct phenotypes in HNC patients suffering from late-RAD, and examine potential correlations between safety and efficacy parameters. A retrospective analysis included twenty-four post-radiotherapy HNC patients evaluated using standardized FEES protocols across three bolus consistencies (liquid, semisolid, and solid). Swallowing safety was quantified using the Penetration–Aspiration Scale (PAS), while efficacy was measured via the Yale Pharyngeal Residue Severity Rating Scale (YPRSRS). Additionally, six distinct dysphagia phenotypes were characterized within the cohort. Propulsion deficit was the predominant phenotype (92%), followed by delayed pharyngeal phase (37.5%) and protective deficit (25%), with 46% of patients exhibiting multiple phenotypes. Unsafe swallowing occurred most frequently with liquid consistency (62.5%), while residue was most prevalent with semisolid (82.6% valleculae, 52.2% pyriform sinuses) and solid consistencies (92.3% valleculae, 53.8% pyriform sinuses). Significant correlations were found between penetration–aspiration and pharyngeal residue scores across consistencies (p < 0.05). FEES examination revealed distinct phenotypes in late radiation-associated dysphagia, with a predominance of propulsion deficit and significant interdependence between safety and efficacy parameters. Full article

Breast cancer remains a leading cause of malignancy-related mortality among women, with rising global incidence. While surgical intervention is effective for early-stage breast cancer, drug therapy is indispensable, particularly for triple-negative breast cancer, where treatment options are still limited. Actaea vaginata, a traditional Chinese medicinal herb, has been historically applied for inflammatory conditions, including pharyngitis and stomatitis. However, its antitumor potential remains under-reported. In this study, a cycloartane triterpene saponin, beesioside O (BO), was isolated from this plant. Its antitumor activity was evaluated in vitro. Its potential therapeutic mechanisms were elucidated through network pharmacology. BO exhibited substantial potency in inhibiting breast cancer cells. Network pharmacology analysis uncovered 179 potential pharmacological targets of BO, which were predominantly concentrated in pathways, such as pathways in cancer, the PI3K-Akt signaling pathway, and chemical carcinogenesis receptor activation. Molecular docking analysis indicated that STAT3 exhibited minimal binding energy with BO. Additionally, molecular dynamics simulations verified the conformational stability of the BO-STAT3 complex. Western blot analysis demonstrated that STAT3 was downregulated following administration. These results imply that BO may exhibit a multi-target, synergistic therapeutic effect against breast cancer, with STAT3 recognized as a pivotal target. This study demonstrates the potential of BO for development as a chemotherapeutic agent for breast cancer treatment. It lays the groundwork for further exploration of BO’s bioactivity and provides valuable insights into its molecular mechanisms in breast cancer therapy. Full article