Breast Cancer Research Articles

Treatment utilization and non-drug interventions for vasomotor symptoms in breast cancer survivors taking endocrine therapy: Real-world findings from the United States and Europe

ObjectivesVasomotor symptoms induced by endocrine therapy are common in breast cancer survivors and a risk factor for therapy discontinuation and lower quality of life. The REALISE study evaluated the real-world treatment landscape in breast cancer survivors with vasomotor symptoms taking endocrine therapy, including pharmaceuticals, lifestyle changes, and over-the-counter products. Study designSecondary analysis of the Adelphi Vasomotor Disease Specific Programme™, a large cross-sectional point-in-time survey and chart review conducted in the US and five European countries (February–October 2020). Oncologists provided demographic, clinical, and treatment data for adult breast cancer survivors with induced vasomotor symptoms taking endocrine therapy (tamoxifen or aromatase inhibitors); patients voluntarily completed self-report surveys on their symptom severity, concomitant sleep and/or mood symptoms, lifestyle changes, and use of over-the-counter products. Main outcome measuresPatient characteristics; vasomotor symptom severity; use of pharmaceuticals, lifestyle changes, and over-the-counter products (from pre-defined lists); lines of treatment. ResultsOverall, 77 oncologists reported data for 618 breast cancer survivors, of whom 183 (29.6 %) completed self-report forms. Physicians classified 420 (68.0 %) women as experiencing moderate-severe vasomotor symptoms, of whom 66.9 % were receiving treatment. In total, 15.2 % of all breast cancer survivors were prescribed systemic hormone therapy. Venlafaxine (24.7 %), citalopram (16.5 %), and paroxetine (13.6 %) were the most commonly prescribed nonhormonal medications. Lifestyle changes (77.8 %) and over-the-counter products (61.6 %) were common, especially in patients with concomitant sleep and/or mood symptoms. ConclusionsDespite contraindications, a relatively large proportion of treatment-seeking breast cancer survivors with vasomotor symptoms were prescribed systemic hormone therapy. This, combined with high patient-reported use of lifestyle changes and over-the-counter products, suggests a need for symptomatic relief and demand for new nonhormonal alternatives with established safety profiles in this population.

Gold Nanocluster: A Photoelectric Converter for X-Ray-Activated Chemotherapy.

Despite the promise of activatable chemotherapy, the development of a spatiotemporally controllable strategy for prodrug activation in deep tissues remains challenging. Herein, a proof-of-concept is proposed for a gold nanocluster-based strategy that utilizes X-ray irradiation to trigger the liberation of platinum (Pt)-based prodrug conjugates, thus enabling radiotherapy-directed chemotherapy. Mechanistically, the irradiated activation of prodrugs is achieved through direct photoelectron transfer from the excited-state gold nanoclusters to the Pt(IV) center, resulting in the release of cytotoxic Pt(II) agents. Compared to the traditional combination of chemotherapy and radiotherapy, this radiotherapy-directed chemotherapy strategy offers superior antitumor efficacy and safety benefits through spatiotemporal synergy at the tumor site. Additionally, this strategy elicits robust immunogenic cell death and yields profound outcomes for combined immunotherapy of breast cancer. This versatile strategy is ushering in a new era of radiation-mediated chemistry for controlled drug delivery and the precise regulation of biological processes.

Residual Nodal Burden After Neoadjuvant Chemotherapy in cN1 Breast Cancer Patients with Positive Nodes at Targeted Axillary Dissection.

Targeted axillary dissection (TAD) facilitates nodal staging in cN1 breast cancer after neoadjuvant chemotherapy (NAC). Completion axillary node dissection (cALND) remains the standard of care for TAD-positive patients. This study investigated factors associated with additional positive nodes at cALND (cALND+) and the impact on the residual cancer burden (RCB). Retrospective review of cN1 breast cancer patients treated with NAC and TAD was conducted from July 2013 to June 2023. The review defined cN1 status by ultrasound (US) and biopsy. Patient, tumor, and treatment characteristics were evaluated. Multivariate analysis was performed to identify factors associated with cALND+, and RCB was calculated. Of 902 patients who underwent TAD, 554 (61.4%) were TAD-positive. 457 underwent cALND, and 124 (27%) were cALND+ (average 4.1 additional +nodes). The cALND+ patients had larger primary tumors at diagnosis (4 vs 3.5 cm; p=0.04), more than three suspicious nodes on initial US (30% vs 13%; p≤0.0001), larger residual primary tumors on pathology (median, 3 vs 2.1 cm; p=0.0004), and more positive TAD nodes (median, 2 vs 1; p≤0.0001). In the multivariate analysis, the factors associated with cALND+ were more than three suspicious nodes on initial US (odds ratio [OR], 2.9; p≤0.0001), more positive TAD nodes (OR, 1.1; p≤0.0001), larger clipped node metastasis (OR, 1.1; p≤0.0001), and larger residual tumor on pathology (OR, 1.1; p=0.006). Of 65 cALND+ patients with RCB class I or II, 29 (45%) had an increase in RCB based on cALND. Of cN1 breast cancer patients treated with NAC who are TAD-positive, approximately 25% will have additional nodal disease on cALND. In these patients, positive cALND is associated with greater disease burden, which has potential implications for RCB status and prognosis.

A highly emissive near infrared thiophene-benzoindolium ligand binding to mitochondrial G-quadruplexes triggers triple-negative breast cancer cell death

Small-molecule fluorescent ligands targeting mitochondrial G-quadruplexes (mtG4s) are considered as a promising direction in tumor therapy, especially those with dual roles of both detecting the mtG4 structures and interfering with the mtG4 functions. Herein, based on our previous studies, two novel thiophene-benzoindolium ligands (YS-1 and YS-2) were designed and synthesized. One of them, YS-2, may be a potential NIR fluorescent probe, with an absorption band centered at 595nm and an emission band centered at 685nm, as well as a good quantum yield upon binding G4s. YS-2 was further proved to selectively bind to mtG4s in MDA-MB-231 cells, and then induce mitochondrial dysfunction, showing suppressive effects on the proliferation of tumor cells in both 2D and 3D cell models. To sum up, a novel highly emissive NIR ligand binding to mtG4s was successfully discovered, giving insights into the future development of novel G4 fluorescent ligands targeting mtG4s with therapeutic possibilities against tumors.

Protease-Responsive Bitext Editing Biopolymer for Breast Cancer Imaging In Vivo

Protease-Responsive Bitext Editing Biopolymer for Breast Cancer Imaging In Vivo

Novel Thienopyrimidine-Hydrazinyl Compounds Induce DRP1-Mediated Non-Apoptotic Cell Death in Triple-Negative Breast Cancer Cells

Novel Thienopyrimidine-Hydrazinyl Compounds Induce DRP1-Mediated Non-Apoptotic Cell Death in Triple-Negative Breast Cancer Cells

ASO Author Reflections: First Descriptions of Patients with Pregnancy Associated Breast Cancer and Subsequent Pregnancy.

ASO Author Reflections: First Descriptions of Patients with Pregnancy Associated Breast Cancer and Subsequent Pregnancy.

Organizational impact of systemic implementation of digital breast tomosynthesis as a primary test for breast cancer screening in Italy.

We present a comprehensive investigation into the organizational, social, and ethical impact of implementing digital breast tomosynthesis (DBT) as a primary test for breast cancer screening in Italy. The analyses aimed to assess the feasibility of DBT specifically for all women aged 45-74, women aged 45-49 only, or those with dense breasts only. Questions were framed according to the European Network of Health Technology Assessment (EuNetHTA) Screening Core Model to produce evidence for the resources, equity, acceptability, and feasibility domains of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) decision framework. The study integrated evidence from the literature, the MAITA DBT trials, and Italian pilot programs. Structured interviews, surveys, and systematic reviews were conducted to gather data on organizational impact, acceptability among women, reading and acquisition times, and the technical requirements of DBT in screening. Implementing DBT could significantly affect the screening program, primarily due to increased reading times and the need for additional human resources (radiologists and radiographers). Participation rates in DBT screening were similar, if not better, to those observed with standard digital mammography, indicating good acceptability among women. The study also highlighted the necessity for specific training for radiographers. The interviewed key persons unanimously considered feasible tailored screening strategies based on breast density or age, but they require effective communication with the target population. An increase in radiologists' and radiographers' workload limits the feasibility of DBT screening. Tailored screening strategies may maximize the benefits of DBT while mitigating potential challenges.

Minimal Functionalization of Ruthenium Compounds with Enhanced Photoreactivity against Hard-to-Treat Cancer Cells and Resistant Bacteria.

Metallocompounds have emerged as promising new anticancer agents, which can also exhibit properties to be used in photodynamic therapy. Here, we prepared two ruthenium-based compounds with a 2,2'-bipyridine ligand conjugated to an anthracenyl moiety. These compounds coded GRBA and GRPA contain 2,2'-bipyridine or 1,10-phenathroline as auxiliary ligands, respectively, which provide quite a distinct behavior. Notably, compound GRPA exhibited remarkably high photoproduction of singlet oxygen even in water (ϕΔ = 0.96), almost twice that of GRBA (ϕΔ = 0.52). On the other hand, this latter produced twice more superoxide and hydroxyl radical species than GRPA, which may be due to the modulation of their excited state. Interestingly, GRPA exhibited a modest binding to DNA (Kb = 4.51 × 104), while GRBA did not show a measurable interaction only noticed by circular dichroism measurements. Studies with bacteria showed a great antimicrobial effect, including a synergistic effect in combination with commercial antibiotics. Besides that, GRBA showed very low or no cytotoxicity against four mammalian cells, including a hard-to-treat MDA-MB-231, triple-negative human breast cancer. Potent activities were measured for GRBA upon blue light irradiation, where IC50 of 43 and 13 nmol L-1 were seen against hard-to-treat triple-negative human breast cancer (MDA-MB-231) and ovarian cancer cells (A2780), respectively. These promising results are an interesting case of a simple modification with expressive enhancement of biological activity that deserves further biological studies.

Low-Cost Early Detection Device for Breast Cancer based on Skin Surface Temperature

Low-Cost Early Detection Device for Breast Cancer based on Skin Surface Temperature

Newer combination treatments for breast cancer coexisting with acute myeloid leukemia in the novel regimens era: A case report and literature review

Newer combination treatments for breast cancer coexisting with acute myeloid leukemia in the novel regimens era: A case report and literature review

Scar Decompression in Managing Breast Cancer-Related Lymphedema: Is it Needed?

Mastectomy, axillary lymph node dissection, and irradiation for breast cancer commonly result in perivascular and axillary scarring. This scarring is thought to cause functional venous stenosis that leads to downstream venous hypertension in the affected extremity. Standard surgical practice is to decompress perivascular scarring at the time of physiologic lymphedema surgery in patients with breast cancer-related lymphedema (BCRL). However, it is unknown whether this scar release influences surgical outcomes. The purpose of this study is to evaluate prevalence of functional venous stenosis in patients with BCRL and determine whether scar decompression is a necessary step in physiologic lymphedema surgery. The authors conducted a retrospective review of 64 patients with unilateral BCRL that presented to our lymphedema center between January 2020 and October 2022. Radiologist reports of venous duplex ultrasound for the bilateral upper extremities identified any disturbances in venous flow or indications of venous stenosis. Of the 64 patients with BCRL, 78% (n=50) had prior axillary lymph node dissection. Forty-seven (73%) patients completed ultrasound imaging, of which, one patient (2%) had venous stenosis in the affected lymphedematous extremity identified on duplex ultrasound that may have suggested functional scarring. Vascularized lymph node transfer (VLNT) without scar decompression was performed in six patients (9%). Average preoperative lymphedema life impact scale (LLIS) and L-dex scores were 35 and 19 units, with a mean decrease of 23 (67%) and 6 (30%) units postoperatively. Most patients with BCRL did not have identifiable functional venous stenosis on duplex ultrasound, apart from one patient with suspected post-thrombotic changes. All six patients that received VLNT without scar decompression had a successful outcome with decreased measures of lymphedema postoperatively. Scar decompression may therefore be unnecessary in physiologic lymphedema surgery, reducing operative times and avoiding risk of injury to neurovascular structures of the axilla.

HER2-targeted therapies beyond breast cancer - an update.

The receptor tyrosine-kinase HER2 (also known as ErbB2) is a well-established therapeutic target in patients with breast or gastric cancer selected on the basis of HER2 overexpression on immunohistochemistry and/or ERBB2 amplification on in situ hybridization. With advances in cancer molecular profiling and increased implementation of precision medicine approaches into oncology practice, actionable HER2 alterations in solid tumours have expanded to include ERBB2 mutations in addition to traditional HER2 overexpression and ERBB2 amplification. These various HER2 alterations can be found in solid tumour types beyond breast and gastric cancer, although few HER2-targeted therapeutic options have been established for the other tumour types. Nevertheless, during the 5 years since our previous Review on this topic was published in this journal, obvious and fruitful progress in the development of HER2-targeted therapies has been made, including new disease indications, innovative drugs with diverse mechanisms of action and novel frameworks for approval by regulatory authorities. These advances have culminated in the recent histology-agnostic approval of the anti-HER2 antibody-drug conjugate trastuzumab deruxtecan for patients with HER2-overexpressing solid tumours. In this new Review, we provide an update on the current development landscape of HER2-targeted therapies beyond breast cancer, as well as anticipated future HER2-directed treatment strategies to overcome resistance and thereby improve efficacy and patient outcomes.

Tracking the epidemiological trends of female breast cancer in Saudi Arabia since 1990 and forecasting future statistics using global burden of disease data, time-series analysis

BackgroundFemale breast cancer stands as the prime type of cancer in the Kingdom of Saudi Arabia (KSA), with a high incidence and mortality rates. This study assessed the burden of female breast cancer in KSA by analyzing and forecasting its incidence, mortality, and disability-adjusted life years (DALYs).MethodsWe retrieved data from the Global Burden of Disease (GBD) about female breast cancer from 1990 to 2021. Time-series analysis used the autoregressive integrated moving average (ARIMA) model to forecast female breast cancer statistics from 2022 to 2026.ResultsFrom 1990 to 2021, KSA reported 77,513 cases of female breast cancer. The age groups with the highest number of cases are 45–49 years, followed by 40–44 years, 50–54 years, and 35–39 years. The analysis also showed fewer cases in the younger age groups, with the lowest number in the less than 20-year-old age group. From 1990 to 2021, KSA reported 19,440 deaths due to breast cancer, increasing from 201 cases in 1990 to 1,190 cases in 2021. The age-standardized incidence rate/100,000 of breast cancer increased from 15.4 (95% confidence interval (CI) 11.2–21.0) in 1990 to 46.0 (95%CI 34.5–61.5) in 2021. The forecasted incidence rate of female breast cancer will be 46.5 (95%CI 45.8–46.5) in 2022 and 49.6 (95%CI 46.8–52.3) in 2026. The age-standardized death rate per 100,000 Saudi women with breast cancer increased from 6.73 (95%CI 6.73–9.03) in 1990 to 9.77 (95%CI 7.63–13.00) in 2021. The forecasted female breast cancer death rate will slightly decrease to 9.67 (95%CI 9.49–9.84) in 2022 and to 9.26 (95%CI 8.37–10.15) in 2026. DALYs increased from 229.2 (95%CI 165.7–313.6) in 1990 to 346.1 (95%CI 253.9–467.2) in 2021. The forecasted DALYs of female breast cancer will slightly decrease to 343.3 (95%CI 337.2–349.5) in 2022 reaching 332.1 (95%CI 301.2–363.1) in 2026.ConclusionsFemale breast cancer is still a significant public health burden that challenges the health system in KSA, current policies and interventions should be fashioned to alleviate the disease morbidity and mortality and mitigate its future burden.

High Sensitivity and Specificity Platform to Validate MicroRNA Biomarkers in Cancer and Human Diseases

We developed a technology for detecting and quantifying trace nucleic acids using a bracketing protocol designed to yield a copy number with approximately ± 20% accuracy across all concentrations. The microRNAs (miRNAs) let-7b, miR-15b, miR-21, miR-375 and miR-141 were measured in serum and urine samples from healthy subjects and patients with breast, prostate or pancreatic cancer. Detection and quantification were amplification-free and enabled using osmium-tagged probes and MinION, a nanopore array detection device. Combined serum from healthy men (Sigma-Aldrich, St. Louis, MO, USA #H6914) was used as a reference. Total RNA isolated from biospecimens using commercial kits was used as the miRNA source. The unprecedented ± 20% accuracy led to the conclusion that miRNA copy numbers must be normalized to the same RNA content, which in turn illustrates (i) independence from age, sex and ethnicity, as well as (ii) equivalence between serum and urine. miR-21, miR-375 and miR-141 copies in cancers were 1.8-fold overexpressed, exhibited zero overlap with healthy samples and had a p-value of 1.6 × 10−22, tentatively validating each miRNA as a multi-cancer biomarker. miR-15b was confirmed to be cancer-independent, whereas let-7b appeared to be a cancer biomarker for prostate and breast cancer, but not for pancreatic cancer.

FANCI Inhibition Induces PARP1 Redistribution to Enhance the Efficacy of PARP Inhibitors in Breast Cancer.

Breast cancer is a global public health concern with high mortality rates, necessitating the development of innovative treatment strategies. PARP inhibitors have shown efficacy in certain patient populations, but their application is largely limited to cancers with homologous recombination deficiency. Here, we identified the suppression of FANCI as a therapeutic strategy to enhance the efficacy of PARP inhibitors in breast cancer. Elevated FANCI expression in breast cancer was associated with poor prognosis and increased cell proliferation and migration. FANCI interacted with PARP1, and suppressing FANCI limited the nuclear localization and functionality of PARP1. Importantly, FANCI inhibition sensitized breast cancer cells to the PARP inhibitor talazoparib in the absence of BRCA mutations. Additionally, the CDK4/6 inhibitor palbociclib enhanced the sensitivity of breast cancer cells to talazoparib through FANCI inhibition. These findings highlight the potential of targeting FANCI to enhance the efficacy of PARP inhibitors in treating breast cancer.

Downregulation of tRF-Cys-GCA-029 by hyperglycemia promotes tumorigenesis and glycolysis of diabetic breast cancer through upregulating PRKCG translation

BackgroundDiabetes mellitus (DM) affects up to one-third of breast cancer (BC) patients. Patients with co-existing BC and DM (BC-DM) have worsened BC prognosis. Nevertheless, the molecular mechanisms orchestrating BC-DM prognosis remain poorly understood. tRNA-derived fragments (tRFs) have been shown to regulate cancer progression. However, the biological role of tRFs in BC-DM has not been explored.MethodstRF levels in tumor tissues and cells were detected by tRF sequencing and qRT-PCR. The effects of tRF on BC cell malignancy were assessed under euglycemic and hyperglycemic conditions in vitro. Metabolic changes were assessed by lactate, pyruvate, and extracellular acidification rate (ECAR) assays. Diabetic animal model was used to evaluate the impacts of tRF on BC tumor growth. RNA-sequencing (RNA-seq), qRT-PCR, Western blot, polysome profiling, luciferase reporter assay, and rescue experiments were performed to explore the regulatory mechanisms of tRF in BC-DM.ResultsWe identified that tRF-Cys-GCA-029 was downregulated in BC-DM tissues and under hyperglycemia conditions in BC cells. Functionally, downregulation of tRF-Cys-GCA-029 promoted BC cell proliferation and migration in a glucose level-dependent manner. tRF-Cys-GCA-029 knockdown also enhanced glycolysis metabolism in BC cells, indicated by increasing lactate/pyruvate production and ECAR levels. Notably, injection of tRF-Cys-GCA-029 mimic significantly suppressed BC tumor growth in diabetic-mice. Mechanistically, tRF-Cys-GCA-029 regulated BC cell malignancy and glycolysis via interacting with PRKCG in two ways: binding to the coding sequence (CDS) of PRKCG mRNA to regulate its transcription and altering polysomal PRKCG mRNA expression to modify its translation.ConclusionsHyperglycemia-downregulated tRF-Cys-GCA-029 enhances the malignancy and glycolysis of BC cells. tRF-Cys-GCA-029-PRKCG-glycolysis axis may be a potential therapeutic target against BC-DM.Graphical

Multi-class Breast Cancer Classification Using CNN Features Hybridization

Breast cancer has become the leading cause of cancer mortality among women worldwide. The timely diagnosis of such cancer is always in demand among researchers. This research pours light on improving the design of computer-aided detection (CAD) for earlier breast cancer classification. Meanwhile, the design of CAD tools using deep learning is becoming popular and robust in biomedical classification systems. However, deep learning gives inadequate performance when used for multilabel classification problems, especially if the dataset has an uneven distribution of output targets. And this problem is prevalent in publicly available breast cancer datasets. To overcome this, the paper integrates the learning and discrimination ability of multiple convolution neural networks such as VGG16, VGG19, ResNet50, and DenseNet121 architectures for breast cancer classification. Accordingly, the approach of fusion of hybrid deep features (FHDF) is proposed to capture more potential information and attain improved classification performance. This way, the research utilizes digital mammogram images for earlier breast tumor detection. The proposed approach is evaluated on three public breast cancer datasets: mammographic image analysis society (MIAS), curated breast imaging subset of digital database for screening mammography (CBIS-DDSM), and INbreast databases. The attained results are then compared with base convolutional neural networks (CNN) architectures and the late fusion approach. For MIAS, CBIS-DDSM, and INbreast datasets, the proposed FHDF approach provides maximum performance of 98.706%, 97.734%, and 98.834% of accuracy in classifying three classes of breast cancer severities.

A unified approach for breast cancer discrimination using metasurface-based microwave technology

Multifocal (MF) and multicentric (MC) breast cancers are more likely to be aggressive than unifocal (UF) breast tumors, and they are linked to high recurrence probability, lymph node metastases, and low survival rates. Metastasis is the process through which cancer cells spread to different body areas. Although the longevity of patients with metastatic breast cancer is high, it is restricted by the growth of brain metastases. Medical imaging techniques have inherent limits. Hence, a precise and sensitive substitution is required. Because microwave imaging is portable, non-ionizing, and affordable, it has become a viable method for the detection of breast cancer. As far as we know, this is the first research aiming at discriminating MF and MC breast cancers from UF ones. This proposal presents a 2×2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$2\ imes 2$$\\end{document} planar metasurface-based array antenna in the Industrial Scientific Medical frequency band at 2.4 GHz. The proposed array configuration significantly enhanced the gain to 4 dBi rather than a single element at 50 Ω. The geometric arrangement of the four antenna elements is optimized to discriminate the critical stage of breast cancers (UF, MF, or MC). As the proposed structure does not surround the breast, it contributes to a higher degree of comfort than the conventional antenna configurations. The magnitude and phase of S-parameters of the backscattered signals are analyzed in this research.

In-silico screening of bioactive compounds of Moringa oleifera as potential inhibitors targeting HIF-1α/VEGF/GLUT-1 pathway against Breast Cancer.

Breast cancer is among the most heterogeneous and aggressive diseases and a foremost cause of death in women globally. Hypoxic activation of HIF-1α in breast cancers triggers the transcription of a battery of genes encoding proteins that facilitate tumor growth and metastasis and is correlated with a poor prognosis. Based on the reported cytotoxic and anti-cancer properties of Moringa oleifera (Mo), this study explores the inhibitory effect of bioactive compounds from M.oleifera and breast cancer target proteins HIF-1α, VEGF, and GLUT-1 in silico. The X-ray crystallographic structures of HIF-1α, VEGF, and GLUT1 were sourced from the Protein Data Bank(PDB) and docked with 70 3D PubChem structures of bioactive compounds of M.oleifera using AutoDock Vina, and binding modes were analyzed using Discovery Studio. Five compounds with the highest binding energies were selected and further drug-likeness, oral bioavailability, ADME, and toxicity profiles were analyzed using SwissADME, ADMETSaR, and ADMETlab 3.0 web server. Out of the screened 70 bioactive compounds, the top five compounds with the best binding energies were identified namely Apigenin, Ellagic Acid, Isorhamnetin, Luteolin, and Myricetin with each receptor. Molecular docking results indicated that the ligands interact strongly with the target HIF-1α, VEGF, and GLUT-1 receptors through hydrogen bonds and hydrophobic interactions. These compounds showed favorable drug-like and pharmacokinetic properties, possessed no substantial toxicity, and were fairly bioavailable. Results suggested that the compounds possess strong potential in developing putative lead compounds targeting HIF-1α that are safe natural plant-based drugs against breast cancer.