Treatment Of Breast Cancer Research Articles

Preexisting Diabetes and Breast Cancer Treatment Among Low-Income Women

Diabetes is associated with poorer prognosis of patients with breast cancer. The association between diabetes and adjuvant therapies for breast cancer remains uncertain. To comprehensively examine the associations of preexisting diabetes with radiotherapy, chemotherapy, and endocrine therapy in low-income women with breast cancer. This population-based cohort study included women younger than 65 years diagnosed with nonmetastatic breast cancer from 2007 through 2015, followed up through 2016, continuously enrolled in Medicaid, and identified from the linked Missouri Cancer Registry and Medicaid claims data set. Data were analyzed from January 2022 to October 2023. Preexisting diabetes. Logistic regression was used to estimate odds ratios (ORs) of utilization (yes/no), timely initiation (≤90 days postsurgery), and completion of radiotherapy and chemotherapy, as well as adherence (medication possession ratio ≥80%) and persistence (<90-consecutive day gap) of endocrine therapy in the first year of treatment for women with diabetes compared with women without diabetes. Analyses were adjusted for sociodemographic and tumor factors. Among 3704 women undergoing definitive surgery, the mean (SD) age was 51.4 (8.6) years, 1038 (28.1%) were non-Hispanic Black, 2598 (70.1%) were non-Hispanic White, 765 (20.7%) had a diabetes history, 2369 (64.0%) received radiotherapy, 2237 (60.4%) had chemotherapy, and 2505 (67.6%) took endocrine therapy. Compared with women without diabetes, women with diabetes were less likely to utilize radiotherapy (OR, 0.67; 95% CI, 0.53-0.86), receive chemotherapy (OR, 0.67; 95% CI, 0.48-0.93), complete chemotherapy (OR, 0.71; 95% CI, 0.50-0.99), and be adherent to endocrine therapy (OR, 0.71; 95% CI, 0.56-0.91). There were no significant associations of diabetes with utilization (OR, 0.95; 95% CI, 0.71-1.28) and persistence (OR, 1.09; 95% CI, 0.88-1.36) of endocrine therapy, timely initiation of radiotherapy (OR, 1.09; 95% CI, 0.86-1.38) and chemotherapy (OR, 1.09; 95% CI, 0.77-1.55), or completion of radiotherapy (OR, 1.25; 95% CI, 0.91-1.71). In this cohort study, preexisting diabetes was associated with subpar adjuvant therapies for breast cancer among low-income women. Improving diabetes management during cancer treatment is particularly important for low-income women with breast cancer who may have been disproportionately affected by diabetes and are likely to experience disparities in cancer treatment and outcomes.

Cerebrospinal venous obstruction and breast cancer: A pilot study.

The venous drainage of the breasts is described and the cerebrospinal venous systems (CSVS) of six patients with treated breast cancer were assessed using duplex ultrasound to measure venous blood volume flows in the neck veins. All six patients with breast cancer showed evidence of cerebrospinal venous obstruction (CSVO). Further, all six demonstrated collateral flow in the erect position in the internal jugular vein on the same side as the diagnosed breast cancer. There is an indication for a well-designed case-control study using the duplex ultrasound neck vein examination, comparing patients treated for breast cancer with healthy women.

Polyphyllin VII Promotes Apoptosis in Breast Cancer by Inhibiting MAPK/ERK Signaling Pathway through Downregulation of SOS1.

Polyphyllin VII is a biologically active herbal monomer extracted from the traditional Chinese herbal medicine Chonglou. Many studies have demonstrated the anticancer activity of polyphyllin VII against various types of cancers, such as colon, liver, and lung cancer, but its effect on breast cancer has not been elucidated. In this study, we demonstrate that polyphyllin VII inhibited proliferation, increased production of intracellular reactive oxygen species, and decreased mitochondrial membrane potential in breast cancer cells. Notably, polyphyllin VII also induced apoptosis via the mitochondrial pathway. Transcriptome sequencing was used to analyze the targets of PPVII in regulating breast cancer cells. Mechanistic studies showed that polyphyllin VII downregulated Son of Sevenless1 (SOS1) and inhibited the MAPK/ERK pathway. Furthermore, PPVII exerted strong antitumor effects in vivo in nude mice injected with breast cancer cells. Our results suggest that PPVII may promote apoptosis through regulating the SOS1/MAPK/ERK pathway, making it a possible candidate target for the treatment of breast cancer.

Royal jelly and its hormonal effects in breast cancer: a literature review.

Breast cancer is the most common cancer in women which can be cured in most individuals with early-stage non-metastatic disease. Imbalance in estrogen signaling pathways and propagating levels of estrogens has important roles in breast cancer development. Targeting the estrogen receptor signaling pathway is linked to breast cancer treatment. Royal jelly is one of the bee products containing 10-hydroxy-2-decenoic acid, a structure similar to mammalian estrogen, allowing it to attach to estrogen receptors. It is considered as a general tonic and immunomodulator which may be helpful in reducing the side effects of cancer treatments. Currently, there are controversial data regarding the pros and cons of royal jelly in cancer. Here we provide an overview of the effects of royal jelly on sex hormones and its possible role in breast cancer. Electronic databases including PubMed, Scopus, and Web of Science were searched with the search terms royal jelly, cancer, and sexual hormones. All preclinical and clinical studies regarding the hormonal effects of royal jelly were included. According to the collected preclinical data, consumption of royal jelly at daily doses below 200mg/kg can be useful to decrease the risk of breast cancer since it reduces the serum level of estrogen; whereas increases progesterone, which subsequently decreases the expression of ERs on the ER-positive cells. Future clinical studies are essential to confirm the safe dose of royal jelly as an adjuvant therapy in breast cancer.

Cancer cell membrane cloaked fluorescent liposomes loaded with metal-phenolic complex nanoparticles for combinatorial therapy against breast cancer

The development of innovative strategies for effective cancer treatment remains a critical research focus. In this study, we present a novel approach by designing cancer cell membrane-cloaked fluorescent liposomes loaded with metal-phenolic complex nanoparticles for combinatorial therapy against breast cancer. This multifaceted therapeutic system leverages the unique properties of cancer cell membranes, fluorescent liposomes, and metal-phenolic complexes to create a highly targeted and versatile treatment platform. Cancer cell membranes serve as natural camouflage, allowing these nanoparticles to evade the immune system and specifically target breast cancer cells. The inclusion of fluorescent liposomes not only aids in real-time imaging of treatment progress but also enhances the therapeutic effect by providing photodynamic therapy. Metal-phenolic complexes provide a multifunctional payload, offering both thermally assisted cytotoxicity and the ability to modulate cellular pathways critical in cancer progression. The enhanced internalization found in 4T1 cell lines demonstrates the targeted efficiency of our nanosystem. We also observed a significant increase in intracellular reactive oxygen species (ROS), increased cell death, and a significant decrease in colony formation treated with the synthesized nanoparticles. Alteration in mitochondrial membrane potential indicated the onset of cellular apoptosis, which eventually resulted in cell death. The biomimetic CSpFeTA NPs exhibited remarkable deep tumor tissue penetration and apoptotic cell death assisted by NIR irradiation. The development of such a sophisticated nanosystem represents a significant advancement in cancer therapy, opening new avenues for personalized and effective breast cancer treatment.

Case report: Treatment with Phesgo® in a patient receiving hemodialysis

IntroductionPatients with metastatic HER2-positive breast cancer have multiple therapeutic options. However, most are not studied in the renal replacement therapy (RRT) setting.Case reportWe report the use of Phesgo® (subcutaneous fixed-dose combination of trastuzumab and pertuzumab) combined with exemestane as a first-line treatment of metastatic HER2-positive breast cancer in a hemodialysis patient with multiple comorbidities. Partial response was attained, with disease progression after 8 months without evidence of significant toxicity.DiscussionsThis case report is, to our knowledge, the first published case documenting the use of Phesgo® in a hemodialysis patient. No new safety signs were seen, and activity was documented, adding support to the use of this drug combination in such a patient population.

Breast cancer incidence, stage distribution, and treatment shifts during the 2020 COVID-19 pandemic: a nationwide population-level study

BackgroundThe first COVID-19 wave in 2020 necessitated temporary suspension of non-essential medical services including organized cancer screening programs in Belgium. This study assessed the impact of the pandemic on breast cancer (BC) incidence, stage at diagnosis, and management in Belgium in 2020.MethodsAll Belgian residents diagnosed with in situ or invasive BC in 2015–2020 in the nationwide, population-based cancer registry database were included. Incidence trends for 2015–2019 were extrapolated to predict incidence and stage distribution for 2020 and compared with the observed values. National healthcare reimbursement data were used to examine treatment strategies. Exact tumor diameter and nodal involvement, extracted from pathology reports, were analyzed for 2019 and 2020.Results74,975 tumors were selected for analysis of incidence and clinical stage. Invasive BC incidence declined by -5.0% in 2020, with a drop during the first COVID-19 wave (Mar-Jun; -23%) followed by a rebound (Jul-Dec; +7%). Predicted and observed incidence (in situ + invasive) was not different in patients < 50 years. In the 50–69 and 70 + age groups, significant declines of -4.1% and − 8.4% respectively were found. Excess declines were seen in clinical stage 0 and I in Mar-Jun, without excess increases in clinical stage II-IV tumors in Jul-Dec. There was no increase in average tumor diameter or nodal involvement in 2020. Patients diagnosed in Mar-Jun received significantly more neoadjuvant therapy, particularly neoadjuvant hormonal therapy for patients with clinical stage I-II BC.ConclusionsBC incidence decline in 2020 in Belgium was largely restricted to very early-stage BC and patients aged 50 and over. Delayed diagnosis did not result in an overall progression to higher stage at diagnosis in 2020. Observed treatment adaptations in Belgium were successful in prioritizing patients for surgery while preventing tumor progression in those with surgical delay. Continuation of monitoring BC incidence and stage in the future is crucial.

THE FORMULATION AND EVALUATION OF 6-THIOGUANINE AS A NANOSTRUCTURE LIPID CARRIER FOR THE TARGETED DELIVERY OF BREAST CANCER

Objective: The main goal was to avoid all the problems associated with usual breast cancer treatment by using 6-thioguanine as a nanostructure lipid carrier (TG-NLCS). This was accomplished by administering an effective and targeted dose of 6-thioguanine (TG) to the tumour site using a long-lasting and biodegradable delivery system. Methods: A combination of heat homogenization and ultrasonication was used to implement the emulsification process. To obtain the optimal formulation, the prepared formulations were first assessed for particle size, Polydispersity Index (PDI), zeta potential, entrapment efficiency, and drug loading capacity. Additionally, a range of physicochemical characterization techniques were employed, including dissolution studies, melting point determination, Fourier-Transform Infrared (FTIR) spectroscopy, and Field Emission Scanning Electron Microscopy (FESEM), as well as cytotoxicity assessment of TG-NLCs in MCF-7 breast cancer cells. Results: The selected formula, TG03, showed a zeta potential of-13.5±0.27 mV and a particle size of 149±0.55 nm. This was further examined using a FESEM. In the in vitro drug release study, the formula demonstrated better-controlled drug release for 48 h in comparison to other formulations. In addition, the significant anti-proliferation activity of TG-NLCs against the MCF-7 breast cancer cell line. Conclusion: Nanostructured lipid carriers (NLCs) are one type of multifunctional nanoparticle that includes many combinations of lipids and medicines for various delivery routes.

THE APPLICATION OF BIOANALYTICAL METHOD OF TAMOXIFEN AND ITS ACTIVE METABOLITES FOR THERAPEUTIC DRUG MONITORING IN BREAST CANCER PATIENTS: A REVIEW

Breast cancer is the most common cancer around the world and in Indonesia. The most widely used agent for breast cancer treatment is tamoxifen, with a fixed dose of 20 mg per day. Tamoxifen is metabolized by cytochrome P450 3A4 (CYP3A4) and 2D6 (CYP2D6) to endoxifen and 4-hydroxytamoxifen, which have 30-to 100-fold more potent antiestrogenic activity than tamoxifen. High variations of CYP3A4 and CYP2D6 genes can lead to interpatient variability in its metabolites concentration. The dose can be increased to 40 or 60 mg per day based on individual needs. Therapeutic drug monitoring (TDM) is required to measure the concentration of tamoxifen and its metabolites to decide the individualized dose. The measurement of drug levels should use a sensitive, selective, accurate, precise, and reliable bioanalytical method. Various bioanalytical methods have been developed in several matrices: urine, scalp hair, serum, plasma, dried blood spot (DBS), and volumetric absorptive microsampling (VAMS) samples, with different sample preparations, and frequently using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The bioanalytical method of tamoxifen and its metabolites in the DBS sample was more suitable in the TDM application due to the low invasive sampling technique, more stable sample, and rapid sample preparation. Therefore, it is more time-and cost-efficient than the other methods.

Ablative technologies in the treatment of breast cancer: a literature review

Ablative technologies in the treatment of breast cancer: a literature review

Magnetic resonance imaging findings of radiation-induced breast angiosarcoma: A case report

BACKGROUND Breast conservation surgery (BCS) with adjuvant radiotherapy has become a gold standard in the treatment of early-stage breast cancer, significantly reducing the risk of tumor recurrence. However, this treatment is associated with adverse effects, including the rare but aggressive radiation-induced angiosarcoma (RIAS). Despite its rarity and nonspecific initial presentation, RIAS presents a challenging diagnosis, emphasizing the importance of imaging techniques for early detection and accurate diagnosis. CASE SUMMARY We present a case of a 48-year-old post-menopausal woman who developed skin ecchymosis on the right breast seven years after receiving BCS and adjuvant radiotherapy for breast cancer. Initial mammography and ultrasound were inconclusive, showing post-treatment changes but failing to identify the underlying angiosarcoma. Contrast-enhanced breast magnetic resonance imaging (MRI) revealed diffuse skin thickening and nodularity with distinctive enhancement kinetics, leading to the diagnosis of RIAS. This case highlights the crucial role of MRI in diagnosing and determining the extent of RIAS, facilitating timely and appropriate surgical intervention. CONCLUSION Breast MRI is crucial for detecting RIAS, especially when mammography and ultrasound are inconclusive.

Breast Conserving Surgery Post Neo-Adjuvant Chemotherapy for Locally Advanced Breast Carcinoma in a Developing Country: Is It Safe?

Breast conserving surgery (BCS) is the standard treatment for early breast cancer and has similar survival with mastectomy. The role of BCS in locally advanced breast cancer (LABC), post neoadjuvant chemotherapy (NACT), is controversial. Surgeons, especially in developing countries, fear higher margin involvement and local recurrence (LR) in BCS. The aim of this study was to determine the LR in BCS compared to mastectomy in LABC post NACT and to ascertain the percentage of involved surgical margins following both methods of surgery. This was a retrospective study of breast cancer patients seen in Universiti Kebangsaan Malaysia Medical Centre (UKMMC). All patients had NACT followed by either mastectomy or BCS. The patients with Her2 enriched carcinomas did not have access to targeted therapy (Trastuzumab or Pertuzumab). The patients with ill-defined tumours underwent ultrasound assessment in the surgical clinics. All had post-operative radiotherapy. All with ER or PR positive cancers were given Tamoxifen for a minimum of 5 years. This study demonstrated that BCS post NACT was safe to be performed in selected patients with LABC in a developing country.

Enzyme-responsive mannose-grafted magnetic nanoparticles for breast and liver cancer therapy and tumor-associated macrophage immunomodulation

ABSTRACT Background Chemo-immunotherapy modifies the tumor microenvironment to enhance the immune response and improve chemotherapy. This study introduces a dual-armed chemo-immunotherapy strategy combating breast tumor progression while re-polarizing Tumor-Associated Macrophage (TAM) using prodigiosin-loaded mannan-coated magnetic nanoparticles (PG@M-MNPs). Methods The physicochemical properties of one-step synthetized M-MNPs were analyzed, including X-ray diffraction, FTIR, DLS, VSM, TEM, zeta potential analysis, and drug loading content were carried out. Biocompatibility, cancer specificity, cellular uptake, and distribution of PG@M-MNPs were investigated using fluorescence and confocal laser scanning microscopy, and flow cytometry. Furthermore, the expression levels of IL-6 and ARG-1 after treatment with PG and PG@M-MNPs on M1 and M2 macrophage subsets were studied. Results The M-MNPs were successfully synthesized and characterized, demonstrating a size below 100 nm. The release kinetics of PG from M-MNPs showed sustained and controlled patterns, with enzyme-triggered release. Cytotoxicity assessments revealed an enhanced selectivity of PG@M-MNPs against cancer cells and minimal effects on normal cells. Additionally, immuno-modulatory activity demonstrates the potential of PG@M-MNPs to change the polarization dynamics of macrophages. Conclusion These findings highlight the potential of a targeted approach to breast cancer treatment, offering new avenues for improved therapeutic outcomes and patient survival.

Berberine inhibits the progression of breast cancer by regulating METTL3-mediated m6A modification of FGF7 mRNA.

Berberine (BBR), an isoquinoline alkaloid from Coptidis rhizoma, has been found to have powerful activities against various human malignancies, including breast cancer. However, the underlying antitumor mechanisms of BBR in breast cancer remain poorly understood. Breast cancer cells were cultured and treated with different doses (0, 20, 40, and 60 μM) of BBR for 48 h. Cell viability, proliferation, apoptosis, invasion, and migration were assessed using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell, and wound healing assays. Fibroblast growth factor 7 (FGF7), methyltransferase-like 3 (METTL3), and insulin-like growth factor-2 mRNA-binding protein 3 (IGF2BP3) mRNA levels and protein levels were measured using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. Interaction between METTL3 and FGF7 m6A was assessed using methylated RNA immunoprecipitation (MeRIP)-qPCR and RNA immunoprecipitation (RIP) assay. Binding ability between IGF2BP3 and FGF7 mRNA was analyzed using RIP assay. BBR treatment hindered breast cancer cell proliferation, invasion, migration, and induced apoptosis. FGF7 expression was upregulated in breast cancer tissues, while its level was reduced in BBR-treated tumor cells. FGF7 upregulation relieved the repression of BBR on breast cancer cell malignant behaviors. In mechanism, METTL3 stabilized FGF7 mRNA through the m6A-IGF2BP3-dependent mechanism and naturally improved FGF7 expression. BBR treatment inhibited breast cancer growth in vivo. BBR treatment blocked breast cancer cell growth and metastasis partly by regulating METTL3-mediated m6A modification of FGF7 mRNA, providing a promising therapeutic target for breast cancer treatment.

Novel Pyrazole-Chalcone Hybrids: Synthesis and Computational Insights Against Breast Cancer.

More women die of breast cancer than of any other malignancy. The resistance and toxicity of traditional hormone therapy created an urgent need for potential molecules for treating breast cancer effectively. Novel biphenyl-substituted pyrazole chalcones linked to a pyrrolidine ring were designed by using a hybridization approach. The hybrids were assessed against MCF-7 and MDA-MB-231 cells by NRU assay. Among them, 8k, 8d, 8m, 8h, and 8f showed significantly potent IC50 values: 0.17, 5.48, 8.13, 20.51, and 23.61 µM) respectively, on MCF-7 cells compared to the positive control Raloxifene and Tamoxifen. Furthermore, most active compound 8k [3-(3-(4-fluorophenyl)-1-phenyl-1H-pyrazol-4-yl)-1-(2-(2-(pyrrolidin-1-yl)-ethoxy)-phenyl)-chalcone] showed cell death induced through apoptosis, cell cycle arrest at the G2/M phase, and demonstrated decrease of ER-α protein in western blotting study. Docking studies of 8k and 8d established adequate interactions with estrogen receptor-α as required for SERM binding. The active hybrids exhibited good pharmacokinetic properties for oral bioavailability and drug-likeness. Whereas, RMSD, RMSF, and Rg values from Molecular dynamics studies stipulated stability of the complex formed between compound 8k and receptor. All of these findings strongly indicate the antiproliferative potential of pyrazole-chalcone hybrids for the treatment of breast cancer.

Redox-Sensitive Poly(lactic-co-glycolic acid) Nanoparticles of Palbociclib: Development, Ultrasound/Photoacoustic Imaging, and Smart Breast Cancer Therapy.

Breast cancer is one of the leading causes of mortality in women globally. The efficacy of breast cancer treatments, notably chemotherapy, is hampered by inadequate localized delivery of anticancer agents to the tumor site, resulting in compromised efficacy and increased systemic toxicity. In this study, we have developed redox-sensitive poly(lactic-co-glycolic acid) (PLGA) nanoparticles for the smart delivery of palbociclib (PLB) to breast cancer. The particle size of formulated PLB@PLGA-NPs (nonredox-sensitive) and RS-PLB@PLGA-NPs (redox-sensitive) NPs were 187.1 ± 1.8 nm and 193.7 ± 1.5 nm, respectively. The zeta potentials of nonredox-sensitive and redox-sensitive NPs were +24.99 ± 2.67 mV and +9.095 ± 1.87 mV, respectively. The developed NPs were characterized for morphological and various physicochemical parameters such as SEM, TEM, XRD, DSC, TGA, XPS, etc. The % entrapment efficiency of PLB@PLGA-NPs and RS-PLB@PLGA-NPs was found to be 85.48 ± 1.29% and 87.72 ± 1.55%, respectively. RS-PLB@PLGA-NPs displayed a rapid drug release at acidic pH and a higher GSH concentration compared to PLB@PLGA-NPs. The cytotoxicity assay in MCF-7 cells suggested that PLB@PLGA-NPs and RS-PLB@PLGA-NPs were 5.24-fold and 14.53-fold higher cytotoxic compared to the free PLB, respectively. Further, the cellular uptake study demonstrated that redox-sensitive NPs had significantly higher cellular uptake compared to nonredox-sensitive NPs and free Coumarin 6 dye. Additionally, AO/EtBr assay and reactive oxygen species analysis confirmed the superior activity of RS-PLB@PLGA-NPs over PLB@PLGA-NPs and free PLB. In vivo anticancer activity in dimethyl-benz(a)anthracene-induced breast cancer rats depicted that RS-PLB@PLGA-NPs was highly effective in reducing the tumor size, hypoxic tumor, and tumor vascularity compared to PLB@PLGA-NPs and free PLB. Further, hemocompatibility study reveals that the developed NPs were nonhemolytic to human blood. Moreover, an in vivo histopathology study confirmed that both nanoparticles were safe and nontoxic to the vital organs.

Androgen receptor: Structure, signaling, function and potential drug discovery biomarker in different breast cancer subtypes.

The Androgen Receptor (AR) is emerging as an important factor in the pathogenesis of breast cancer (BC), which is the most common malignancy worldwide. >70 % of AR expression in primary and metastatic breast tumors has been observed which suggests that AR may be a new marker and a potential therapeutic target among AR-positive BC patients. Biological insight into AR-positive breast cancer reveals that AR may cross-talk with several vital signaling pathways, including key molecules and receptors. Downstream signaling of AR might also affect many clinically important pathways that are emerging as clinical targets in BC. AR exhibits different behaviors depending on the breast cancer molecular subtype. Preliminary clinical research using AR-targeted drugs, which have already been FDA-approved for prostate cancer (PC), has given promising results for AR-positive breast cancer patients. However, since AR positivity's prognostic and predictive value remains uncertain, it is difficult to identify and stratify patients who would benefit from AR-targeted therapies alone. Thus, the need of the hour is to target the androgen receptor as a monotherapy or in combination with other conventional therapies which has proven to be an effective clinical strategy for the treatment of prostate cancer patients, and these therapeutic strategies are increasingly being investigated in breast cancer. Therefore, in this manuscript, we review the role of AR in various cellular processes that promote tumorigenesis and aggressiveness, in different subtypes of breast cancer, as well as discuss ongoing efforts to target AR for the more effective treatment and prevention of breast cancer.

Targeted blocking of EGFR and GLUT1 by compound H reveals a new strategy for treatment of triple-negative breast cancer and nasopharyngeal carcinoma

BackgroundCytoplasmic epidermal growth factor receptor (EGFR) is overexpressed in both nasopharyngeal carcinoma (NPC) and triple-negative breast cancer (TNBC), while clinical outcome and prognosis vary greatly among patients treated with gefitinib, and all patients eventually develop resistance to this agent. Therefore, we propose a new concept for synthesizing multitarget compounds and reveal new therapeutic strategies for NPC and TNBC expressing EGFR. MethodsCompound H was synthesized in our previous study. Molecular docking, and cell thermal shift assays (CETSAs) and drug affinity responsive target stability(DARTS) were used to confirm the binding of compound H to EGFR and GLUT1. Methylthiazolyldiphenyl-tetrazolium bromide(MTT), annexin V-PE assays, mitochondrial membrane potential (MMP) assays, and animal models were used to evaluate the inhibitory effect of compound H on TNBC cell lines. Energy metabolism tests, Western blotting, and immunofluorescence staining were performed to evaluate the synergistic effects on EGFR- and glucose transporter type 1(GLUT1)-mediated energy metabolism. ResultsCompound H can simultaneously act on the EGFR tyrosine kinase ATP-binding site and inhibit GLUT1-mediated energy metabolism, resulting in reductions in ATP, MMP, intra-cellular lactic acid, and EGFR nuclear transfer. The anti-tumor activity of compound H is significantly superior to the combination of GLUT1 inhibitor BAY876 and EGFR inhibitor gefitinib. Compound H has remarkable anti-proliferative effects on TNBC MDA-MB231 cells, and importantly, no obvious toxicity effects of compound H were found in vivo. ConclusionsSynergistic effects of inhibition of EGFR- and GLUT1-mediated energy metabolism by compound H may present a new strategy for the treatment of TNBC and NPC.

Impact of the COVID-19 pandemic on breast cancer patient pathways and outcomes in the United Kingdom and the Republic of Ireland - a scoping review.

The COVID-19 pandemic brought unplanned service disruption for breast cancer diagnostic, treatment and support services. This scoping review describes these changes and their impact in the UK and the Republic of Ireland based on studies published between January 2020 and August 2023. Thirty-four of 569 papers were included. Data were extracted and results thematically organized. Findings include fewer new cases; stage shift (fewer early- and more late-stage disease); and changes to healthcare organization, breast screening and treatment. Examples are accepting fewer referrals, applying stricter referral criteria and relying more on virtual consultations and multi-disciplinary meetings. Screening service programs paused during the pandemic before enacting risk-based phased restarts with longer appointment times to accommodate reduced staffing numbers and enhanced infection-control regimes. Treatments shifted from predominantly conventional to hypofractionated radiotherapy, fewer surgical procedures and increased use of bridging endocrine therapy. The long-term impact of such changes are unknown so definitive guidelines for future emergencies are not yet available. Cancer registries, with their large sample sizes and population coverage, are well placed to monitor changes to stage and survival despite difficulties obtaining definitive staging during diagnosis because surgery and pathological assessments are delayed. Multisite longitudinal studies can also provide guidance for future disaster preparedness.

Assessment of Hypoxia in Breast Cancer: Emerging Functional MR Imaging and Spectroscopy Techniques and Clinical Applications.

Breast cancer is one of the most prevalent forms of cancer affecting women worldwide. Hypoxia, a condition characterized by insufficient oxygen supply in tumor tissues, is closely associated with tumor aggressiveness, resistance to therapy, and poor clinical outcomes. Accurate assessment of tumor hypoxia can guide treatment decisions, predict therapy response, and contribute to the development of targeted therapeutic interventions. Over the years, functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS) techniques have emerged as promising noninvasive imaging options for evaluating hypoxia in cancer. Such techniques include blood oxygen level-dependent (BOLD) MRI, oxygen-enhanced MRI (OE) MRI, chemical exchange saturation transfer (CEST) MRI, and proton MRS (1H-MRS). These may help overcome the limitations of the routinely used dynamic contrast-enhanced (DCE) MRI and diffusion-weighted imaging (DWI) techniques, contributing to better diagnosis and understanding of the biological features of breast cancer. This review aims to provide a comprehensive overview of the emerging functional MRI and MRS techniques for assessing hypoxia in breast cancer, along with their evolving clinical applications. The integration of these techniques in clinical practice holds promising implications for breast cancer management. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 1.