Original research publications

Mass spectrometry-based metabolomics is a useful strategy for characterizing metabolic remodeling in cancer cells and evaluating complex botanical formulations. This study investigated the anti-breast cancer effects of Shentong Zhuyu Decoction (STZYD) by integrating UPLC-QTOF/MS-based chemical profiling, untargeted metabolomics, network pharmacology, molecular docking, and Western blotting. STZYD inhibited the viability of MDA-MB-231 and MCF-7 cells in a dose-dependent manner, with IC 50 values of 11.57 and 18.26 mg/mL, respectively. UPLC-QTOF/MS initially detected 2493 chromatographic-mass spectrometric features in the STZYD extract, which were curated into 889 nonredundant putatively annotated compounds. Cellular metabolomics revealed 233 differential metabolites, with glycolysis/gluconeogenesis being one of the most significantly enriched pathways. STZYD treatment altered the abundance of glycolysis/gluconeogenesis-related metabolites, including d-glucose, G6P/F6P, PEP, pyruvate, and lactate, suggesting glycolysis-related metabolic remodeling. Network pharmacology and molecular docking predicted the PI3K/AKT axis as a potential regulatory pathway. Western blotting showed that STZYD decreased PI3K, AKT, p-PI3K, and p-AKT levels. These findings suggest that STZYD exerts anti-breast cancer effects in vitro, at least partly through PI3K/AKT-associated glycolysis-related metabolic remodeling.

Cerebellopontine angle (CPA) tumors are predominantly vestibular schwannomas and meningiomas; metastatic lesions in this location are rare, particularly in the absence of multiple brain metastases. We report the case of a 53-year-old woman with a history of invasive ductal carcinoma of the breast in HER2-positive metastatic relapse, in whom brain MRI revealed a single 28 × 24 mm mass in the right cerebellopontine angle. The lesion was isointense on T1- and T2-weighted images, contained fluid components, and showed restricted diffusion (ADC 0.64 × 10⁻³ mm²/s) with intense peripheral enhancement after gadolinium administration. MR spectroscopy demonstrated markedly elevated Cho/NAA (6.73) and Cho/Cr (5.72) ratios within the lesion, with a normal perilesional spectroscopic profile, favoring a secondary lesion and allowing the main differential diagnoses to be excluded without biopsy. The patient underwent stereotactic radiotherapy (30 Gy in 5 fractions), with significant regression of the lesion on follow-up MRI at five months. This case illustrates the role of MR spectroscopy in the non-invasive characterization of atypical cerebellopontine angle lesions.

To assess the inter-reader agreement in background parenchymal enhancement (BPE) categorization on ultrafast dynamic contrast-enhanced (DCE) MRI before and after training and its relationship with breast cancer prognostic factors. We retrospectively analyzed the cases of 220 patients (median, age 60 years; 220 breast cancers) who underwent ultrafast DCE MRI. BPE was qualitatively classified as minimal, mild, moderate, or marked by three readers: Reader1 (R1), a radiology resident in the second year of training; Reader2 (R2), an experienced general radiologist with 28 years of experience in diagnostic radiology; and Reader3 (R3), an experienced breast radiologist with 25 years of experience in breast MRI. Inter-reader agreement was evaluated using weighted kappa (κ) values and was reassessed between R1 and R3 after intensive training. Associations between BPE levels and prognostic factors were also evaluated. Inter-reader agreement was substantial with weighted κ values of 0.679-0.742 for R1 versus R2, 0.612-0.665 for R1 versus R3, and 0.626-0.689 for R2 versus R3. Agreement between R1 and R3 improved slightly after training but remained substantial. No significant associations were observed between visual BPE classification and prognostic factors, including hormone receptor status, HER2 status, and proliferation markers. Inter-reader agreement for BPE assessment on ultrafast DCE MRI was substantial and improved slightly after training. No significant relationship was observed between ultrafast BPE and breast cancer prognostic factors.

The benefit of neoadjuvant chemotherapy (NAC) in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) remains uncertain, given low pathologically documented complete response (pCR) rates and limited long-term comparative data. We compared overall survival (OS) between NAC and adjuvant chemotherapy (AC) in luminal B-like breast cancer treated in routine practice. Patients enrolled in the prospective French CANTO cohort between January 2012 and December 2018 with unilateral, nonmetastatic, grade 3 HR-positive/HER2-negative BC (cT2-T3N0-N3M0) treated with NAC followed by surgery or with primary surgery followed by AC were included. The primary endpoint was OS; secondary endpoints were distant recurrence-free survival (DRFS) and invasive disease-free survival; exploratory endpoints were BC-specific survival, locoregional recurrence-free survival (LRFS) and breast recurrence-free survival. Inverse probability of treatment weighting (IPTW) was applied, with weighted Kaplan-Meier estimates and Cox models. Among 544 patients, 165 received NAC and 379 AC; median follow-up was 72 months. Breast-conserving surgery was more frequent after NAC (64% compared with 45%, P < 0.001) and the pCR rate was 19%. After IPTW, the hazard ratio for OS with NAC was 1.36 [95% confidence interval (CI) 0.94-1.97, P = 0.10] univariably and 1.62 (95% CI 1.10-2.38, P = 0.014) after multivariable adjustment. No difference was observed for DRFS (hazard ratio 1.05, 95% CI 0.80-1.38, P = 0.70). LRFS was worse with NAC (hazard ratio 2.29, 95% CI 1.15-4.58, P = 0.018) in 19 events. In interaction tests, the association with OS was confined to cN0 (hazard ratio 2.39) and cT2 (hazard ratio 1.94) disease and absent in cN+ (hazard ratio 0.83) and cT3 (hazard ratio 0.88) tumors. NAC was associated with more locoregional recurrence without any difference in DRFS and the association with OS was confined to subgroups in whom a neoadjuvant indication is least established. These hypothesis-generating findings do not support the routine use of NAC in luminal B-like BC without an anticipated surgical benefit.

Lifeguard (LFG/FAIM2) is an anti-apoptotic transmembrane protein implicated in apoptosis resistance and breast cancer progression. However, the molecular mechanisms underlying its biological function remain incompletely understood. In the present study, we investigated potential interactions between LFG and phosphoinositides in the breast cancer cell line MDA-MB-231. Using membrane lipid strip and phosphoinositide (PIP) array assays, we observed binding signals between LFG and several phosphoinositide species, indicating potential lipid-binding preferences under the experimental conditions employed. Because phosphoinositides participate in intracellular calcium signaling pathways, we next examined whether reduced LFG expression was associated with alterations in intracellular calcium homeostasis. Using a fluorescence-based calcium assay, we found that siRNA-mediated downregulation of LFG was associated with increased intracellular calcium-associated fluorescence. Overall, our exploratory findings suggest that LFG may participate in phosphoinositide-associated signaling and intracellular calcium homeostasis in the breast cancer cell model examined. Further studies will be required to validate these observations, determine the underlying molecular mechanisms, and assess their potential relevance for apoptosis regulation and breast cancer progression.

Bone metastases represent a frequent complication of breast cancer, affecting more than one third of patients. Delayed investigation of persistent focal bone pain in a breast cancer patient can lead to serious consequences. We report a case of delayed radiographic diagnosis of distal femur metastases in a breast cancer patient, where the initial standard X-ray was normal. The diagnosis of bone metastasis was established by a second X-ray 11 months later, following disease progression. This case highlights the limitations of conventional radiography and highlights the importance of using PET-CT, MRI, or bone scintigraphy imaging modalities methods for early detection of metastatic lesions to guide therapeutic management.

To explore how women of reproductive age with breast cancer experience the impact of moderate-to-severe chemotherapy-induced nausea and vomiting (CINV) on motherhood and family roles. A descriptive qualitative study was conducted using semi-structured interviews. Sixteen women of reproductive age with breast cancer who had experienced moderate-to-severe CINV during chemotherapy were recruited through purposive sampling with a maximum variation strategy. CINV severity was assessed with reference to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Interviews were audio-recorded, transcribed verbatim, and analyzed using reflexive thematic analysis following Braun and Clarke's six-phase approach. Four themes were identified: (1) Triggered disruptions in mothering, describing how smell-triggered nausea and difficulties with physical closeness interrupted everyday mothering practices; (2) Visible challenges to maternal competence, reflecting mothers' experiences when nausea and vomiting became visible to children and children responded to their distress; (3) Symptom-driven redistribution of mothering work, describing the temporary transfer of childcare responsibilities to spouses, parents, and parents-in-law during symptom episodes; and (4) Gaps between CINV management and mothering needs, highlighting limited mothering-related guidance and professional support during home-based symptom peaks. Moderate-to-severe CINV may become intertwined with everyday mothering and family caregiving among women with breast cancer. The findings highlight the potential value of considering caregiving disruption and family-role needs alongside conventional symptom management and may inform the future development and evaluation of mother-sensitive, family-oriented supportive care.

Assessing and trackinghuman epidermal growth factor receptor 2 (HER2) status in breast cancer (BC) is essential for selecting the right targeted therapies, but conventional tissue biopsies fall short because they cannot fully reflect tumor heterogeneity or provide ongoing, real-time monitoring. Circulating tumor cells (CTCs) provide a minimally invasive way to dynamically assess HER2 status, but they still require further validation and standardization before routine clinical use. We compared the HER2 expression on CTCs through a quantitative assessment using the ACCEPT tool across patients with BC with different HER2 status on tissue (positive, low and null). The proportion of HER2-expressing CTCs in individual samples (CTC-HER2ratio) was calculated and correlation with tissue HER2 status was analyzed in a cohort of patients with metastatic BC (MBC) to define an optimal cutoff value for discrimination by receiver operating characteristic (ROC) analysis. A total of 143 patients were included. The median CTC-HER2ratio was significantly higher in patients with HER2-positive (HER2+) tumors compared to HER2-negative (HER2-)tumors (30% vs 9%, p = 0.0003). The ROC curve yielded an area under the curve (AUC) of 0.7417 for distinguishing HER2+ from HER2- disease, with an exploratory optimal cutoff of 0.22. In contrast, the CTC-HER2ratio did not significantly differentiate HER2-low from HER2-null tumors (p = 0.327; AUC 0.5646), highlighting limited resolution in the low-expression range. This proof-of-concept study suggests that a ratio-based assessment of HER2 expression on CTCs may capture biological heterogeneity and correlate with tissue HER2 status. However, the modest discriminative performance and limited resolution in the HER2-low range indicate that further prospective validation is necessary before clinical integration.

This study aimed to explore how women with breast cancer perceived potential cardiovascular toxicity and engaged in self-management to support their cardiovascular health, monitor for symptoms, and adhere to clinical surveillance. A qualitative descriptive design was employed. Semi-structured interviews were conducted with a purposively selected sample of 12 women with breast cancer. The interviews were audio-recorded with the participants' consent and transcribed verbatim. NVivo 12 was used to organise the data, which were analysed using inductive thematic analysis to develop themes and subthemes. The study included 12 women aged 40-74 years. Participants reported multiple challenges in recognising and understanding potential cardiovascular toxicity, possible cardiovascular symptoms, and other treatment-related symptoms. Four themes and nine subthemes were identified: (1) overwhelming physical and functional burden of treatment; (2) fragmented knowledge and awareness of potential cardiovascular toxicity; (3) health care communication gaps and unmet informational needs; and (4) psychosocial and systemic barriers to overall well-being and health management. The participants faced substantial barriers to understanding and monitoring for potential cardiovascular toxicity. These challenges highlight the need for the future development and evaluation of more proactive, patient-centred interventions. Proposed strategies, such as tailored education, symptom-reporting tools, and structured follow-up models, require future research to determine their effectiveness.

Breast cancer remains one of the leading causes of cancer-related mortality in women worldwide, despite significant advances in early detection and conventional therapies. Immunotherapy has emerged as a promising strategy to harness the body's immune system to combat tumors. However, limitations such as immune escape mechanisms and inefficient drug delivery continue to challenge its effectiveness. In recent years, engineered exosomes, cell-derived nanoscale vesicles, have gained attention as innovative carriers for cancer immunotherapy due to their natural biocompatibility, low immunogenicity, and inherent targeting capabilities. This review highlights recent advancements in the design and functionalization of exosomes for breast cancer immunotherapy, including the loading of immune-stimulating molecules, genetic cargos, and surface modifications to enhance tumor specificity. We also discuss their advantages over conventional nanocarriers, immunological mechanisms, preclinical evidence, and challenges related to clinical translation. While significant progress has been made, further research is needed to overcome current barriers and fully exploit the potential of engineered exosomes as a next-generation platform in breast cancer immunotherapy.

This study systematically reviewed evidence on the operational pathways and workflow integration of digital symptom management platforms for breast cancer, covering the full process from monitoring to intervention. It summarized response pathway patterns to inform oncology nursing practice. Following the Arksey and O'Malley scoping review framework, we systematically searched seven databases from January 1, 2010 to August 7, 2026. The PCC (Population, Concept, Context) principle was adopted to formulate the inclusion and exclusion criteria. Indicators related to operation and implementation were extracted. A total of 19 publications representing 18 independent studies and 18 unique digital platforms were included. Only a few studies reported implementation details such as data integration with hospital information systems, response time, referral escalation, staff training, and process safety. According to whether clinicians participated in symptom management workflows, we classified the included platforms into two mutually exclusive categories: the clinician-involved pathway ( n = 16) and the patient-alone pathway ( n = 2). Key implementation elements of current digital symptom management platforms for breast cancer, such as system integration and response timeliness, remain insufficiently reported. We established an exploratory classification framework comprising two mutually exclusive categories-the clinician-involved pathway and the patient-alone pathway-which may serve as a reference for oncology nursing practice. Future efforts should establish a standardized reporting framework and conduct cross-setting implementation studies to evaluate the applicability and sustainability of these implementation models. The study protocol is registered in the Open Science Framework (OSF Registry ID: 10.17605/OSF.IO/QPHV3).

Triple-negative breast cancer (TNBC) treatment is often hindered by tumor hypoxia, cellular survival compensation, and the immuno-suppressive micro-environment. Through the "molecular-electron pumping" strategy, a cyanine photosensitizer BrCy5 with excellent Type I ROS generation ability (two kinds of Type I ROS production of BrCy5 are 308% and 206% higher) was developed to realize photodynamic therapy-mediated immunotherapy under tumor hypoxia. In the work, a multifunctional nanoenzyme HMB loaded with Type I photosensitizer was further designed, which precisely delivers BrCy5 and Fe 3+ to tumor cell mitochondria via tumor targeting and lysosomal endocytosis, triggering a lethal cascade of multimodal cell death. Released Fe 3+ catalyzes endogenous H 2 O 2 into O 2 , relieving hypoxia to enhance photodynamic efficacy while depleting glutathione (GSH). Free BrCy5 accumulates in mitochondria, inducing severe mitochondrial dysfunction and lipid peroxidation via efficient ROS generation. This synergistic oxidative stress triggers ferroptosis, activates the Caspase-3/GSDME signaling axis for pyroptosis, leading to massive release of damage-associated molecular patterns (DAMPs) and potent immunogenic cell death (ICD). To enhance this cascade, System Xc - inhibitor sulfasalazine (SSZ) was combined to further deepen GSH depletion and exacerbate ferroptosis. In bilateral tumor-bearing mice, this enhanced regimen created a highly inflamed microenvironment, promoting dendritic cells (DCs) maturation and cytotoxic T lymphocytes (CTLs) infiltration, reversing immunosuppression. Ultimately, it inhibited primary and distant tumor growth, converting "cold" to "hot" breast cancer, proposing a transformative strategy for efficient TNBC treatment by combining the "molecular-electron pumping" photosensitizer, multifunctional nanoenzyme carrier, and metabolic pathway blocking to induce multimodal tumor cell death-induced immunotherapy.

Paclitaxel (PTX) resistance in triple-negative breast cancer (TNBC) is closely associated with ATP-binding cassette (ABC) transporters-medicated drug efflux and hypoxia-driven upregulation of hypoxia-inducible factor-1α (HIF-1α), which together promote tumor progression and metastasis. Although blood transfusion or hyperbaric oxygen therapy can partially alleviate systemic hypoxia, neither approach effectively relieves chemoresistance driven by intratumoral hypoxia. To address this challenge, we have developed a biomimetic hybrid delivery system (red blood cell hitchhiking-liposomes encapsulate hemoglobin and paclitaxel, RBC-LEHP) that utilizes red blood cell-hitchhiking technology along with pH-responsive liposomes, to co-deliver hemoglobin (Hb) and PTX to overcome hypoxia-associated chemoresistance. This system achieves dual-stage targeting: passive sequestration in pulmonary metastatic lesions through erythrocyte hitchhiking and active tumor internalization mediated by pH-sensitive DOPE phospholipids. Our study revealed that RBC-LEHP effectively alleviated the hypoxia microenvironment through Hb-mediated oxygenation upon tumor cellular internalization and downregulated HIF-1α and glutathione peroxidase 4 (GPX4), while simultaneously enhancing reactive oxygen species (ROS)-mediated lipid peroxidation to induce ferroptosis. This amplified oxidative stress further triggered mitochondrial dysfunction, suppressed P-glycoprotein (P-gp)-mediated PTX efflux, reversed PTX resistance, and promoted apoptotic cell death. In vivo results confirmed that RBC-LEHP-mediated therapeutic cascade of "lung targeted delivery → hypoxia alleviation → ferroptosis/chemotherapy → tumor suppression" significantly enhanced antitumor efficacy against TNBC. This biomimetic platform provides a promising strategy for overcoming physiological barriers and chemoresistance in metastatic TNBC therapy.

Breast cancer presents a formidable global health challenge, with traditional monotherapies frequently hampered by limited specificity and off-target toxicity. Herein, we developed a highly integrated, biomimetic, and pH-responsive zeolitic imidazolate framework-8 (ZIF-8) nanoplatform, RBCm-coated nanoparticles (R-A/G@Z), tailored for cascaded starvation and potentiated ferroptosis therapy. Through a one-pot biomineralization approach, the hydrophobic ferroptosis inducer artesunate (ART) and the hydrophilic metabolic enzyme glucose oxidase (GOx) were co-encapsulated within a ZIF-8 framework, followed by red blood cell membrane (RBCm) surface cloaking. The R-A/G@Z platform demonstrates enhanced tumor accumulation and undergoes acid-triggered disassembly within the tumor microenvironment (TME). Upon internalization, GOx-mediated glucose oxidation serves to starve the tumor of its primary energy source while continuously generating hydrogen peroxide (H 2 O 2 ) and protons. This localized acidification accelerates structural degradation, supplying ample H 2 O 2 to fuel an ART-triggered Fenton-like reaction. Crucially, the concurrent liberation of Zn 2+ from the ZIF-8 lattice orchestrates a dual-regulatory axis: it downregulates ferroportin 1 (FPN1) to retain reactive iron intracellularly, and upregulates tumor protein p53 (p53) to suppress the solute carrier family 7 member 11-glutathione-glutathione peroxidase 4 (SLC7A11-GSH-GPX4) antioxidant shield. This integrated strategy overcomes the tumor's redox defenses, leading to ferroptotic cell death. In vitro and in vivo evaluations confirm that R-A/G@Z effectively suppresses aggressive breast tumors while maintaining a good safety profile, offering a promising strategy for intelligent metabolic-chemodynamic cancer nanomedicine.

Triple-negative breast cancer (TNBC) remains a significant clinical challenge due to the lack of actionable targets, dose-limiting cardiotoxicity, and the limited efficacy of single-modality therapies. Doxorubicin (DOX), a first-line chemotherapeutic agent, is constrained by inadequate tumor targeting and systemic toxicity. In this study, we identified an SML peptide with high binding affinity for TNBC through in vitro and in vivo investigations. Fibroblast activation protein-alpha-α (FAP-α), which is highly expressed by cancer-associated fibroblasts (CAFs) within the TNBC tumor microenvironment (TME), was exploited as a tumor-specific trigger for targeted drug release. We developed a TME-responsive self-assembled peptide-based nanoplatform (QGS@DOX, DOX-loaded QGS self-assembled nanocarrier) that integrates g active tumor targeting, FAP-α-triggered cleavage, anti-angiogenic activity, and DOX chemotherapy. QGS@DOX demonstrated enhanced tumor accumulation, prolonged circulation time, and controlled drug release. In vivo, it effectively inhibited tumor growth and metastasis while reducing DOX-induced cardiotoxicity. Mechanistic studies revealed that QGS@DOX suppressed epithelial-mesenchymal transition (EMT), induced immunogenic cell death (ICD), and activated the cGAS-STING pathway, thereby remodeling the TME. Importantly, moesin (MSN) was identified as a novel target of the SML targeting peptide, uncovering a previously unrecognized mechanism for TNBC-specific delivery. To our knowledge, this is the first report of an integrated nanoplatform combining FAP-α responsiveness, SML-MSN targeting, anti-angiogenesis, chemotherapy, and cGAS-STING-mediated immunotherapy for TNBC. These findings present a promising strategy for precise, multimodal treatment of TNBC.

In the phase 3 OptiTROP-Breast01 trial, sacituzumab tirumotecan (sac-TMT) significantly improved progression-free survival versus chemotherapy in patients with previously treated advanced triple-negative breast cancer (TNBC), with a statistically significant overall survival (OS) benefit observed at the prespecified interim OS analysis. Here we report the final OS analysis with extended follow-up. Overall, 263 patients with previously treated locally recurrent or metastatic TNBC were randomly assigned 1:1 to sac-TMT (n=130) or chemotherapy (n=133). OS was a key secondary endpoint. At a median follow-up of 29.4 months, median OS was 14.7 months (95% CI 12.1‒20.1) with sac-TMT and 9.9 months (95% CI 8.6‒11.8) with chemotherapy (HR 0.60, 95% CI 0.45‒0.80); 30-month OS rates were 26.8% and 13.2%. The OS benefit observed at interim analysis was maintained at final analysis and generally consistent across all subgroups. Subsequent antibody-drug conjugate (ADC) therapy was received by 27.8% of patients in the chemotherapy group. After adjustment for subsequent ADC therapy using the rank-preserving structural failure time model, median OS was 14.7 months with sac-TMT and an estimated 9.4 months with chemotherapy (HR 0.55, 95% CI 0.39‒0.73); censoring analysis yielded consistent results (HR 0.59, 95% CI 0.43-0.82). The sac-TMT safety profile remained consistent with previous findings, with no new safety signals. The most common grade ≥3 treatment-related adverse events were decreased neutrophil count, decreased white blood cell count and anemia. Exploratory patient-reported outcome analyses showed numerically longer median time to deterioration with sac-TMT than with chemotherapy across all five evaluated health-related quality-of-life domains, with the largest differences for fatigue and pain. These final OS data after extended follow-up demonstrate a clinically meaningful and sustained OS benefit of sac-TMT versus chemotherapy and further reinforce its role as a treatment option for previously treated advanced TNBC. No new safety signals were identified.

The clinical management of patients with breast cancer is largely dictated by tumor stage, disease subtype and (at least in some settings) specific molecular features thereof ( e.g. , BRCA1 mutations, PD-L1 positivity). However, not all patients with breast cancer respond to therapeutic approaches that a priori are precisely targeted to their disease. At least in part, this may reflect the fact that breast neoplasms are highly heterogeneous from a broad immunological perspective, even when they exhibit similar disease subtype and molecular features. Thus, integrating extra immunological parameters into current decision-making algorithms may considerably improve clinical management in this large patient population. In this context, circulating indicators of global immune fitness and ongoing anticancer immunity stand out as particularly promising tools for minimally invasive prognostic and/or predictive assessments. Here, we summarize and critically discuss the circulating immune landscape of human breast cancer, whenever possible comparing across disease subtypes, stages, and treatment outcomes.

Timely breast cancer care remains challenging in South Africa, where both health-system and patient-level barriers contribute to delayed diagnosis and treatment. This study explored healthcare providers' experiences and perspectives on breast cancer care at Chris Hani Baragwanath Academic Hospital in Soweto and its two referring secondary hospitals in Johannesburg. Using a cross-sectional qualitative design informed by phenomenology, we conducted in-depth interviews with 30 providers involved in breast cancer care. Thematic analysis identified intersecting structural and individual barriers, together with provider-led strategies to improve care delivery. System-level constraints included high patient volumes, staff shortages, limited diagnostic capacity, referral delays, inconsistent treatment supplies, and the absence of radiation oncology services at CHBAH, necessitating referral to an affiliated hospital 25 km away. Providers also described patient-related contributors to delay, including fear, denial, symptom misinterpretation, socioeconomic hardship, and limited self-efficacy, often exacerbated by poor communication. Suggested priorities included community and primary care education, provider training, high-risk screening in primary care, and expanded diagnostic and treatment infrastructure, particularly radiation oncology services at CHBAH. Furthermore, providers described pragmatic mitigation strategies, including expedited diagnostic workup, multidisciplinary coordination, electronic records, NGO-supported patient navigation, and temporary disability grants to offset transport costs. In conclusion, these findings provide a foundation for a coordinated response to strengthen oncology care in resource-constrained settings. Delayed breast cancer detection and treatment are driven by low symptom awareness, lack of primary care screening and referral system inefficiencies.Sociocultural beliefs, economic hardship and limited patient agency further contribute to late presentation and delayed access to care.System-level barriers such as workforce shortages, disrupted treatment supply chains and limited access to radiation oncology undermine timely cancer care.Tertiary providers adopt mitigation strategies, but expanding community education, provider training and referral tracking systems is essential to improve early detection and treatment outcomes.

Although targeted therapies have improved clinical outcomes, HER2+ breast cancer remains a significant clinical challenge due to its aggressive behavior and unfavorable prognosis. Emerging evidence indicates that dysregulated lipid metabolism plays a critical role in tumorigenesis and metastasis, suggesting that targeting lipid metabolism may represent a promising therapeutic strategy. STARD10, a lipid transport protein, plays a pivotal role in regulating lipid metabolism. However, its function in mediating lipid metabolism and tumor progression in HER2+ breast cancer remains unclear. The expression level and prognostic relevance of STARD10 in HER2+ breast cancer were analyzed using public databases and clinical cohorts. CCK-8, EdU, colony formation, transwell, LD540, and Nile Red staining assays were performed in SKBR3 and HCC1954 cells. Subcutaneous implantation and tail vein injection were performed to evaluate the effects of STARD10 overexpression on tumor growth and lung metastasis in vivo. The mechanism was validated by RNA-seq and Western blotting. STARD10 expression was upregulated in HER2+ breast cancer tissues and was significantly correlated with poor prognosis. Functionally, STARD10 overexpression enhanced HER2+ breast cancer cell proliferation, migration, invasion, and lipid droplets accumulation. Moreover, STARD10 overexpression markedly accelerated tumor growth and lung metastasis in vivo. Mechanistically, STARD10 was found to drive malignant phenotypes via activation of the cAMP/PKA/CREB1 signaling axis. STARD10 promotes malignant progression of HER2+ breast cancer and lipid droplets accumulation by activating the cAMP/PKA/CREB1 pathway. These findings suggest that STARD10 and the cAMP/PKA/CREB1 signaling axis as potential therapeutic targets for the treatment and prevention of HER2+ breast cancer.

Bromodomain and extra-terminal (BET) family proteins are important epigenetic readers and play key roles in cancers, inflammatory diseases, and immune disorders. Current BET inhibitors, which function via an occupancy-driven mechanism, are often hampered by drug resistance and limited efficacy. In this study, a series of novel acetylpyrrole-based BET degraders were designed, synthesized, and evaluated, demonstrating notable antitumor effects in both wild-type and drug-resistant models of acute myeloid leukemia (AML) and triple-negative breast cancer (TNBC). Through structural optimization, 36 (F364) was identified as a potent BRD4 degrader, exhibiting a D max of 93.96% and a DC 50 of 0.676 nM in the HiBiT assay using HEK293-BRD4-HiBiT-KI cells, slightly superior to the positive control ARV-825. This compound showed strong antiproliferative activity in MV4-11 cells (IC 50 = 4.99 nM) and displayed marked efficacy against SHP099-resistant MV4-11 cells (IC 50 = 1.62 nM), indicating its potential to overcome resistance to SHP2 inhibitors. Moreover, compound F364 exhibited an IC 50 value of 127.87 nM against MDA-MB-231 cells, demonstrating potent antitumor activity toward solid tumor cells. Mechanistic investigations revealed that the degradation process involves the cereblon (CRBN)-mediated proteasomal pathway. In xenograft mouse models using MV4-11 and MDA-MB-231 cells, F364 demonstrated significant antitumor efficacy without observable toxicity. In summary, F364 has been identified as a novel and potent BRD4 degrader, showing promising therapeutic potential for the treatment of acute myeloid leukemia and triple-negative breast cancer.

Mifepristone (MIF), an antagonist of the progesterone receptor (PR) and glucocorticoid receptor (GR), has shown antitumor activity in experimental breast cancer, but the consistency and certainty of the preclinical evidence remain unclear. We systematically searched PubMed, Embase, Web of Science, and the China National Knowledge Infrastructure through May 5, 2026, for animal studies evaluating MIF alone or in combination with other anticancer treatments. Random-effects meta-analyses were performed using Hedges' g with restricted maximum likelihood estimation and the Knapp-Hartung adjustment. Seventeen studies contributed to the quantitative synthesis. MIF monotherapy was associated with lower tumor volume (Hedges' g = -2.77, 95% confidence interval [CI] -4.07 to -1.47) and tumor weight (Hedges' g = -2.52, 95% CI -4.74 to -0.29), whereas the overall tumor-area estimate was inconclusive (Hedges' g = -0.80, 95% CI -1.77 to 0.16). MIF-containing combination regimens were associated with lower tumor volume than the corresponding MIF-free backbone regimens (Hedges' g = -1.28, 95% CI -1.94 to -0.63). No statistically significant difference in terminal body weight was observed under either treatment framework. Exploratory subgroup analysis identified an interaction between PR isoform context and the tumor-area effect estimate (P for interaction = 0.0004), whereas no evidence of an interaction was observed between the broader breast-cancer biological contexts for tumor volume (P for interaction = 0.769). Heterogeneity was substantial for several outcomes, and the certainty of evidence was low to very low. The available animal evidence supports further investigation of MIF in biologically characterized breast cancer models, but does not establish clinical efficacy, validated predictors of treatment response, or overall treatment safety. PROSPERO: CRD420261386224.

To explore barriers to and facilitators of self-management and related support needs across the pathway from neoadjuvant chemotherapy (NAC) to surgery by integrating the perspectives of patients and health care professionals in an analysis informed by the Integrated Theory of Health Behavior Change (ITHBC). We used a qualitative descriptive design and maximum variation purposive sampling to recruit 16 individuals who were receiving NAC or awaiting surgery, together with 11 health care professionals involved in NAC care or self-management support. Data were collected through face-to-face, semi-structured interviews. The ITHBC informed the interview guides and initial analytic framework. Directed content analysis combined deductive coding guided by the framework with inductive analysis of data not captured by the framework. Patient and health care professional data were analysed separately and then integrated. Four interrelated themes were constructed. First, patients varied in their understanding of why chemotherapy preceded surgery and how to interpret tumor changes; some regarded tumor shrinkage as evidence that treatment was complete. Second, cumulative toxicity constrained nutrition, physical activity, and functional readiness for surgery. Third, day-to-day self-management was shaped by the timeliness and credibility of professional guidance, as well as family and social circumstances. Fourth, the overlap of persistent symptoms, physical recovery, and surgical preparation during the transition from NAC to surgery revealed gaps in transitional support that were not adequately addressed by generic health education. Self-management needs differed across NAC stages and during the transition to surgery. These findings suggest a need for continuous and individualised self-management support aligned with patients' understanding, symptom burden, and treatment stage.

Thermoradiotherapy at 40-43 °C is an effective treatment for locoregional recurrent (LRR) breast cancer patients. During hyperthermia temperature monitoring is often limited to skin temperatures, but their predictive value for achieving locoregional tumor control (LRC) remains unclear for tumor depths ≥1cm. This study compared predictive value of skin versus invasive intratarget temperatures. We reported earlier the thermal dose-effect relationship in 112 patients with LRR breast cancer treated in 2010-2017 with postoperative re-irradiation (8 × 4 Gy/23 × 2 Gy) and 4-5 weekly hyperthermia sessions with 434 MHz microwave applicators. Bolus cooling enabled semi-superficial target depths (1-4 cm), thermocouple thermometry monitored both skin and intratarget temperatures. The present study analyzes relationships between LRC and average skin and intratarget median temperature T 50 and best session with highest median thermal dose CEM43T50 (cumulative equivalent minutes at 43 °C). Pearson correlation coefficient analysis evaluated correlation between intratarget and skin temperature parameters. Average median skin and invasive temperatures were T 50 = 40.6 °C (Interquartile Range IQR 40.3-40.8) and T 50 = 40.7 °C (IQR 40.0-41.3), respectively, without association between skin and intratarget temperatures. Median CEM43T50 for skin and intratarget were 2.8 (IQR 2.0-4.3) and 7.2 min (IQR 3.4-15.9) in the best hyperthermia session, respectively. Twenty-four patients developed infield recurrences; median time-to-recurrence was 3.4 years (IQR 2.7-4.6 years). Univariate and multivariate analysis showed significant association of intratarget temperature parameters with LRC ( p = 0.015; p = 0.021, respectively), but not for skin temperature parameters and LRC ( p = 0.131; p = 0.215, respectively). Temperature monitoring using both skin and invasive intratarget measurements is key for ensuring good quality superficial hyperthermia delivery for tumor depths ≥1cm.

Breast cancer (BC) has a substantial impact on women of working age, making return to work (RTW) a critical outcome to evaluate. Research on RTW relies on individual-level real-world data integrating clinical and occupational information. Luxembourg offers a unique setting for such studies, with a young population and a high number of crossborder workers, creating specific challenges and opportunities for studying RTW. This study aims to describe a secure data linkage framework integrating population-based cancer registry, occupational health records, and questionnaire data to evaluate RTW after BC in Luxembourg. A cross-sectional pilot study was conducted linking data from three sources: from Luxembourg's National Cancer Registry (RNC), occupational health records from the Service de Santé au Travail Multisectoriel (STM), and results from a 27-item self-administered questionnaire. Eligible women were diagnosed with BC between 2013 and 2018, were younger than 65 years, employed under Luxembourgish labour law, and followed by STM. Potential participants were identified through STM records and invited to complete an electronic questionnaire and provide explicit consent for data linkage via REDCap® (Research Electronic Data Capture). A deterministic linkage between RNC and STM was enabled by using a common pseudonymisation service. Sociodemographic, clinical, and work-related characteristics were compared between linked and nonlinked participants and between women who did and did not RTW. Among 452 women contacted, 171 completed the questionnaire and provided informed consent (38% response rate). Ninety-six were successfully linked with the RNC dataset. Having Luxembourg as nationality or country of residence was associated with successful linkage ( P < 0.001). Among linked participants, 74 (77.1%) RTW after BC-related leave. Women who RTW were significantly younger at diagnosis than those who did not, and most resumed work in the same sector and company. Pseudonymised deterministic data linkage across three real-world data sources, including population-based cancer registry data, is feasible, and provides unique insights into RTW after BC. Crossborder residency patterns and heterogeneous cancer definitions between sources were key barriers to complete linkage. The population-based approach enables a more complete picture of RTW trajectories among women with BC, supporting robust real-world evidence and informing RTW surveillance and occupational health policies in highly mobile European crossborder regions.

Residents of food-insecure areas (FIAs) experience worse cancer outcomes, but underlying mechanisms remain poorly understood. Prior studies have not determined whether inequalities result from differences in cancer characteristics, treatment delivery, adherence, or food insecurity (FI) itself. We hypothesized that patients with locally advanced breast cancer (LABC) residing in FIAs would demonstrate worse overall survival (OS) despite receiving similar cancer treatments with comparable treatment adherence. This retrospective study analyzed 943 patients with LABC treated with comprehensive nodal irradiation from 2016 to 2023. χ 2 and Mann-Whitney U tests assessed differences in demographic, clinical, and treatment variables. Kaplan-Meier analysis and multivariable Cox regression models evaluated OS. Median follow-up was 25.0 months for non-FIA and 28.8 months for FIA residents. FIA residents (n = 60; 6.4%) were more likely to identify as Black ( P < .001), and have comorbidities including hypertension ( P < .001), diabetes mellitus (DM; P < .001), and higher ECOG PS ( P <.001). Although categorical obesity rates did not differ between groups at consultation (57.4% vs 42.3%; P = .153), they diverged significantly by follow-up (65.5% vs 40.9%; P < .001). Cancer and treatment characteristics did not differ between groups. Multivariable analysis identified FI (HR, 5.52; 95% CI, 1.76-17.27; P = .003), diabetes mellitus (HR, 2.96; 95% CI, 1.13-7.76; P = .027), and new pulmonary conditions at follow-up (HR, 9.57; 95% CI, 3.46-26.49; P < .001) as independent predictors of mortality. Hormone therapy delivery (HR, 0.12; 95% CI, 0.02-0.95; P = .045) and duration (HR, 0.96; 95% CI, 0.94-0.98; P < .001) were protective. Five-year OS was 74.9% for FIA versus 90.2% for non-FIA residents ( P = .005). Patients with LABC residing in FIAs had a 5.5 times higher mortality risk despite similar cancer characteristics, treatments, and adherence. Higher obesity rates among FIA residents that increased following treatment represent a novel characterization of the FI-obesity paradox in patients with breast cancer. These findings support residence in an FIA as an independent predictor of mortality and suggest that interventions must address nutritional quality and access.

Racial inequities in maternal morbidity and mortality persist in the postpartum period. Postpartum hospital use (PHU), including readmissions and emergency department visits, occurs in 5% to 9% of births, with rates among Black individuals at the higher end of this range. Risk-targeted interventions may improve efficiency and equity by directing resources to those at greatest risk postpartum and addressing structural barriers to care. Building on prior prediction model development and community-engaged intervention design, we conducted a pilot randomized controlled trial using a validated PHU risk calculator to identify and enroll high-risk participants into a postpartum education and patient navigation intervention. To evaluate feasibility and engagement with a postpartum educational and patient navigation intervention and generate preliminary estimates of effectiveness in reducing PHU within 30 days of delivery discharge. We conducted a randomized controlled trial among Black individuals who gave birth at a Philadelphia academic medical center between February 2024 and April 2025. Recruitment was guided by a risk calculator derived from a previously validated prediction model for PHU. Study coordinators abstracted predictor data from medical charts; self-identified Black individuals with ≥5.5% predicted PHU were eligible (cut-point selected from validation). Participants were enrolled before discharge from delivery hospitalization and randomized 1:1 to receive a postpartum educational and patient navigation intervention or standard care. The intervention included bedside printed and electronic education materials, and patient navigation including an in-hospital educational session and support via text message and phone calls through 30 days postpartum. The primary outcome was hospital use within 30 days of discharge, ascertained via electronic medical record and self-report. Secondary outcomes included depressive symptoms, self-efficacy, and perceived access to care self-reported on surveys at 3 weeks postpartum. Feasibility measures, including recruitment yield, retention, and implementation challenges identified from study logs and research team debriefs. Among 1051 individuals screened, 616 (58.6%) were eligible and approached for enrollment, and 220 were enrolled and randomized (110 intervention, 110 control). Use of the risk calculator resulted in a high social vulnerability cohort: 50.0% with annual household income <$45,000 and 14.2% unhoused. Clinical risk scores were similar in intervention and control groups. Coordinators reported challenges to risk calculator use, including time-intensive abstraction, discrepancies between variable definitions in administrative data (model development) and medical records (recruitment), and missing data. The overall 30-day cumulative incidence of PHU was 18.2%. Incidence was 20.0% among intervention participants and 16.4% among control participants (risk ratio [95% confidence interval]=1.2 [0.7-2.0]). Secondary outcomes were similar between groups. Among intervention participants, 79% reported that the educational materials were helpful and 61% reviewed them more than once. Among Black participants at elevated risk, engagement with a postpartum patient navigation and education intervention was high, although preliminary estimates did not suggest reduced PHU. Risk-based recruitment identified a cohort with elevated PHU but posed challenges for real-time risk ascertainment. These findings can inform larger multisite trials of risk-targeted, multilevel postpartum interventions.