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Residual Disease Burden After Neoadjuvant Therapy Among US Patients With High-Risk HER2-positive Early-Stage Breast Cancer A Population Effectiveness Model.

Approximately half of patients with high-risk HER2-positive early-stage breast cancer (ESBC) do not have pathologic complete response (pCR) after neoadjuvant therapy. The residual burden of disease among this population has not been previously quantified. We used decision-modeling techniques to simulate recurrence, progression from locoregional to distant cancer, breast cancer-related mortality, and mortality from other causes over a 10-year period in a hypothetical cohort. We derived progression probabilities primarily from the KATHERINE trial of T-DM1 (ado-trastuzumab emtansine) and mortality outcomes from the published literature. Modeled outcomes included recurrences, breast cancer deaths, deaths from other causes, direct medical costs, and costs due to lost productivity. To estimate the residual disease burden, we compared outcomes from a cohort of patients treated with T-DM1 versus a hypothetical cohort with no disease recurrence. We estimated that 9,300 people would experience incident high-risk HER2-positive ESBC in the United States in 2021 based on cancer surveillance databases, clinical trial data, and expert opinion. We estimated that, in this group, 2,118 would experience disease recurrence, including 1,576 distant recurrences, and 1,358 would experience breast cancer deaths. This residual disease burden resulted in 6,435 life-years lost versus the recurrence-free cohort, and healthcare-related costs totaling $644 million, primarily associated with treating distant cancers. Patients with HER2-positive ESBC who do not achieve pCR after neoadjuvant therapy are at ongoing risk of recurrence despite the effectiveness of neoadjuvant treatment. There is substantial clinical and economic value in further reducing the residual disease burden in this population.

Integrative Expression, Survival Analysis and Cellular miR-2909 Molecular Interplay in MRN Complex Check Point Sensor Genes (MRN-CSG) Involved in Breast Cancer.

Breast cancer, an emerging global challenge, is evidenced by recent studies of miRNAs involvement in DNA repair gene variants (MRE11, RAD50, and NBN as checkpoint sensor genes (CSG) - MRN-CSG). The identification of various mutations in MRN-CSG and their interactions with miRNAs is still not understood. The emerging studies of miR-2909 involvement in other cancers led us to explore its role as molecular mechanistic marker in breast cancer. The genomic and proteomic data of MRN-CSG of breast cancer patients (8426 samples) was evaluated to identify the mutation types linked with the patients survival rate. Additionally, molecular, 3D-structural and functional analysis was performed to identify miR-2909 as regulator of MRN-CSG. The genomic and proteomic data analysis shows genetic alterations with majority of missense mutations RAD50 (0.7%), MRE11 (1.5%), and NBN (11%), though with highest MRE11 mRNA expression in invasive ductal breast carcinoma as compared to other breast cancer types. The Kaplan-Meier survival curves suggest higher survival rate for unaltered groups as compared to the altered group. Network analysis and disease association of miR-2909 and MRN-CSG shows strong interactions with other partners. The molecular hybridization between miR-2909-RAD50 and miR-2909-MRE11 complexes showed thermodynamically stable structures. Further, argonaute protein, involved in RNA silencing, docking studies with miR-MRE11-mRNA and miR-RAD50-mRNA hybridized complexes showed strong binding affinity. The results suggest that miR-2909 forms strong thermodynamically stable molecular hybridized complexes with MRE11 and RAD50 mRNAs which further strongly interacts with argonaute protein to show potential molecular mechanistic role in breast cancer.

Management of ovarian and breast cancer risk in non-BRCA HBOC pathogenic variant carriers in a large California health care system.

To describe breast and ovarian cancer risk reduction strategies in the clinical management of women who test positive for non-BRCA hereditary breast and ovarian cancer (HBOC) pathogenic variants compared to those who test positive for pathogenic BRCA variants or have negative germline panel testing. Examination of imaging and preventive surgeries in women undergoing HBOC genetic testing from 112015 to 12312018, with follow up to 03312020 in Kaiser Permanente Northern California. A total of 13,271 tests which included HBOC genes were identified. Rate of bilateral salpingo-oophorectomy after genetic testing were similar for BRCA and the non-BRCA moderate risk ovarian pathogenic variants (PVs) (47.4% vs 54%, p 0.25). Rates were lower for low risk or unknownrisk non-BRCA PVs (12.8%, p < 0.001, 5.3% (p < 0.001). Rates of surveillance for ovarian cancer with ultrasound and CA 125 in the first year was 63.3% and 64.7% for BRCA PV, 37.5% and 27.1%, for non-BRCA moderate risk PVs and 13.7% and 4.6%, for low-risk PVs. Bilateral mastectomy rates were 19.7% for BRCA PV, 10.1% (p 0.028) for non-BRCA breast high risk PVs, for moderate risk PVs 7.7% (p < 0.001) and for unknown risk 0.4% (p < 0.001). MRI surveillance rates in the first year similarly were 47.4% for non-BRCA BRCA PV, 43% for breast high risk PV, 39.4% for moderate risk and 4.9% for unknown risk PV. Surgical and surveillance strategies are underutilized for HBOC PV, however there is concordance of uptake of preventive strategies with specific risk associated with non-BRCA PVs.

Development, implementation and formative evaluation of a motivational-volitional intervention to promote sustainable physical activity in breast cancer survivors.

The aim of the current project was the development, implementation and evaluation of the programme, Motivational-Volitional Intervention-Movement After Breast Cancer (Mo-Vo-BnB), an intervention for the sustainable promotion of physical activity of breast cancer survivors. In a multi-stage interdisciplinary development process, the pedagogical-didactic, psychological and physical evidence-based programme was developed and implemented for women after breast cancer who were approved for medical rehabilitation and were minimally, physically active (<60 minweek). Train-the-trainer seminars were carried out for the implementation. Four sessions were implemented in two German clinics. The training quality, didactic methods and accompanying material were evaluated 6 weeks and 12 months after implementation by patients, trainers and project members (n 127 evaluations). The standardised and published MoVo-BnB programme can provide practical and quality training. Content and methods can be implemented according to the manual. Training quality, didactic methods, and accompanying materials were evaluated positively. The results suggest that MoVo-BnB is a useful standardised intervention for promoting the physical activity of breast cancer survivors. The demonstrated process is also suitable for other projects. German Clinical Trials Register (DRKS) DRKS00011122 Trial registration date 2016 October 13.

CD8

Immunometabolism has advanced our understanding of how the cellular environment and nutrient availability regulates immune cell fate. Not only are metabolic pathways closely tied to cell signaling and differentiation, but can induce different subsets of immune cells to adopt unique metabolic programs, influencing disease progression. Dysregulation of immune cell metabolism plays an essential role in the progression of several diseases including breast cancer (BC). Metabolic reprogramming plays a critical role in regulating T cell functions. CD8

Passive exposure to electronic cigarette aerosol in pregnancy A case study of a family.

Passive exposure to the aerosols of electronic cigarettes (e-cigarettes) has been little studied. We assessed this exposure in late pregnancy in a woman and her 3-year-old child, exposed through e-cigarette use by another household member. This prospective longitudinal case study involved a family unit consisting of an e-cigarette user, a pregnant woman who delivered an infant during the study, and the couples older 3-year-old son. At 31, 36, and 40 weeks of the pregnancy, we measured biomarkers (nicotine metabolites, tobacco-specific nitrosamines, propanediols, glycerol, and metals) in the urine and hair of all three participants and in the saliva of the adults, in cord blood at delivery, and in the breast milk at the postpartum period. Samples from the e-cigarette user showed quantifiable concentrations of all analytes assessed (maximum urinary cotinine concentration, 4.9 ngmL). Among samples taken from the mother, nicotine and its metabolites were found mainly in urine and also in saliva and hair, but not in cord blood. During the postpartum period, we found cotinine concentrations of 2.2 ngmL in the mothers urine and 0.22 ngmL in breast milk 1,2-propanediol was generally detected in urine and saliva, but not in cord blood or breast milk. The maximum urinary cotinine concentration in the 3-year-old child was 2.6 ngmL and propanediols also were detected in his urine. Nitrosamines were not detected in samples taken from the mother or the 3-year-old. Metals found in the refill liquid were detected at low levels in both the mother and the 3-year-old. We detected low but not negligible concentrations of e-cigarette-related analytes (including cord blood and breast milk) in an exposed pregnant non-user and in a 3-year-old child also living in the home. Passive exposure to e-cigarette aerosols cannot be disregarded and should be assessed in larger observational studies.

Therapeutic Nanocarriers Inhibit Chemotherapy-Induced Breast Cancer Metastasis.

Chemotherapy, although effective against primary tumors, may promote metastasis by causing the release of proinflammatory factors from damaged cells. Here, polymeric nanoparticles that deliver chemotherapeutics and scavenge proinflammatory factors simultaneously to inhibit chemotherapy-induced breast cancer metastasis are developed. The cationic nanoparticles can adsorb cell-free nucleic acids (cfNAs) based on charge-charge interaction, which downregulates the expression of Toll-like receptors and then reduces the secretion of inflammatory cytokines. Through in vitro structural optimization, cationic polyamidoamine (PAMAM) dendrimers modified with drug-binding dodecyl groups and diethylethanolamine surface groups (PAMAM-G3-C12

Predictive and prognostic values of tumor infiltrating lymphocytes in breast cancers treated with neoadjuvant chemotherapy A meta-analysis.

This meta-analysis assessed the predictive and prognostic value of tumor infiltrating lymphocytes (TILs) in neoadjuvant chemotherapy (NACT) treated breast cancer and an optimal threshold for predicting pathologic complete response (pCR). A systematic search of PubMed, EMBASE and Web of Science electronic databases was conducted to identify eligible studies published before April 2022. Either a fixed or random effects model was applied to estimate the pooled hazard ratio (HR) and odds ratio (OR) for prognosis and predictive values of TILs in breast cancer patients treated with NACT. The study is registered with PROSPERO (CRD42020221521). A total of 29 published studies were eligible. Increased levels of TILs predicted response to NACT in HER2 positive breast cancer (OR 2.54 95%CI, 1.50-4.29) and triple negative breast cancer (TNBC) (OR 3.67, 95%CI, 1.93-6.97), but not for hormone receptor (HR) positive breast cancer (OR 1.68, 95 %CI, 0.67-4.25). A threshold of 20% of H E-stained TILs was associated with prediction of pCR in both HER2 positive breast cancer (P 0.035) and TNBC (P 0.001). Moreover, increased levels of TILs (either iTILs or sTILs) were associated with survival benefit in HER2-positive breast cancer and TNBC. However, an increased level of TILs was not a prognostic factor for survival in HR positive breast cancer (pooled HR 0.64, 95%CI 0.03-14.1, P 0.78). Increased levels of TILs were associated with increased rates of response to NACT and improved prognosis for the molecular subtypes of TNBC and HER2-positive breast cancer, but not for patients with HR positive breast cancer. A threshold of 20% TILs was the most powerful outcome prognosticator of pCR.

Impact of baseline telomere length on survival and chemotherapy related toxicity in breast cancer patients receiving (neo)adjuvant anthracycline containing chemotherapy.

The aim of this study is to assess baseline mean leukocyte telomere length (TL) as a potential predictive factor for chemotherapy toxicity and a prognostic marker for long-term outcome in early breast cancer (BC) patients. 445 BC patients were selected, diagnosed between 2007 and 2010 with early BC and treated with (neo)adjuvant fluorouracil, epirubicin and cyclophosphamide (FEC) or with FEC and Docetaxel (FEC-D). RT-qPCR was performed on germline DNA samples collected at diagnosis before any treatment, to measure mean leukocyte TL. Uni- and multivariable logistic regression or Cox proportional hazard regression analyses were carried out to assess correlation between baseline TL and toxicity parameters (derived from the medical chart) or longer-term outcome. Baseline TL correlated with age as expected (p 0.005), but not with febrile neutropenia (n 97), left ventricular ejection fraction >10% decrease (n 17) nor other toxicity endpoints measured (all p > 0.05). TL was neither associated with overall survival, breast cancer specific survival or distant disease-free survival (all p > 0.05). Baseline TL is not associated with chemotherapy-related toxicity nor long-term outcome in BC patients.

Correlation of CT-data derived from multiparametric dual-layer CT-maps with immunohistochemical biomarkers in invasive breast carcinomas.

To examine the correlation of quantitative measurements from material decomposition maps calculated from dual-layer CT (DLCT)-image datasets with immunohistochemical biomarkers of invasive breast carcinomas. All patients at the University Breast Cancer Center who underwent a clinically indicated dual-layer CT-scan for staging of invasive ductal breast carcinoma from 012016 to 072020 were prospectively included. Iodine concentration maps and maps of the effective atomic numbers (Zeffective) were reconstructed from the image datasets. ROI-based evaluations of the index tumors and predefined references tissues for normalization were performed semi-automatically in identical anatomical positions using dedicated evaluation software. Statistical analysis was essentially descriptive using Spearmańs rank correlation and (multivariable) partial correlation. Bivariate showed statistically significant correlations of iodine contents (r -0.154-0.2020.180, p 0.0390.0060.015), and Zeffective-values (r -0.158-0.1990.179, p 0.0340.0070.016) for all 184 carcinomas and the subgroup of 168 invasive ductal carcinomas. The results were confirmed by multivariate analyses with age, diameter and ACR-grade as possible confounders. Normalization of the measured target values with those in the aorta confirmed significant correlations of iodine content and Zeffective compared to Estrogen (r 0.174, p 0.019), Progesteron (r 0.1680.177, p 0.0240.017), and HER2 receptor expression (r -0.222-0.184, p 0.0030.013). All CT-parameters showed significant correlations with immunohistochemical subtyping (r 0.1910.192, p 0.010). Our preliminary results indicate that iodine content and Zeffective-values derived from DLCT-examinations correlate with hormone receptor expression in invasive breast carcinomas. Assignments to benign entities already seam feasible in clinical routine CT-diagnostics. After further investigations iodine content and Zeffective may be translated as diagnostical and prognostical biomarkers into clinical routine in the long term.

Long-term exposure to residential green spaces and site-specific cancer mortality in urban Belgium A 13-year follow-up cohort study.

Residing in greener areas may decrease the burden of chronic diseases, but the association with cancer is unclear. We studied the associations between residential green spaces and site-specific cancer mortality in urban Belgium. We linked the 2001 Belgian census, register mortality data for 2001-2014, and environmental information (green spaces and air pollution) at baseline residence (2001). We included residents from the largest Belgian urban areas aged ≥ 30 years at baseline. Exposure to residential green spaces was assessed using the Normalized Difference Vegetation Index (NDVI), Urban Atlas, and perceived neighbourhood greenness (from the census). We used Cox proportional hazards models to obtain hazard ratios (HR) and their 95 % confidence intervals (95 %CI) of the mortality risk from lung, colorectal, breast (in women) and prostate cancer (in men) per interquartile range increment in residential green spaces. We further analyzed the role of outdoor air pollution and effect modification by age and socioeconomic position (SEP) in main associations. 2,441,566 individuals were included at baseline. During follow-up, 1.2 % died from lung cancer, 0.6 % from colorectal cancer, 0.8 % from breast cancer, and 0.6 % from prostate cancer. After adjustment, higher exposure to green spaces was associated with a reduced mortality risk from lung cancer and breast cancer e.g., for NDVI within 300 m, HR0.946 (95 %CI0.924,0.970), and HR0.927 (95 %CI0.892,0.963), respectively, but not with colorectal or prostate cancer mortality. For the latter, a suggestive hazardous effect of green spaces was found. Air pollution seemed to have only a marginal role. Beneficial effects of greenspace were generally stronger in < 65-year-old, but no clear trend by SEP was found. Our findings suggest that residing in green areas could decrease mortality risk from lung and breast cancer, potentially independent from air pollution. Future studies should consider different indicators of greenspace exposure and investigate potential pathways underlying the associations.

The severity of individual menopausal symptoms, cardiovascular disease, and all-cause mortality in the Womens Health Initiative Observational Cohort.

The aim of this study was to examine the association between common menopausal symptoms (MS) and long-term cardiovascular disease (CVD) and all-cause mortality. In an observational cohort of 80,278 postmenopausal women with no known CVD at baseline from the Womens Health Initiative, we assessed individual MS severity (mild vs none moderatesevere vs none) for night sweats, hot flashes, waking up several times at night, joint pain or stiffness, headaches or migraines, vaginal or genital dryness, heart racing or skipping beats, breast tenderness, dizziness, tremors (shakes), feeling tired, forgetfulness, mood swings, restless or fidgety, and difficulty concentrating. Outcomes included total CVD events (primary) and all-cause mortality (secondary). Associations between specific MS, their severity, and outcomes were assessed during a median of 8.2 years of follow-up. All results were multivariable adjusted, and individual associations were Bonferroni corrected to adjust for multiple comparisons. A machine learning approach (least absolute shrinkage and selection operator) was used to select the most parsimonious set of MS most predictive of CVD and all-cause mortality. The severity of night sweats, waking up several times at night, joint pain or stiffness, heart racing or skipping beats, dizziness, feeling tired, forgetfulness, mood swings, restless or fidgety, and difficulty concentrating were each significantly associated with total CVD. The largest hazard ratio (HR) for total CVD was found for moderate or severe heart racing or skipping beats (HR, 1.55 95% confidence interval CI, 1.29-1.86). The individual severities of heart racing or skipping beats, dizziness, tremors (shakes), feeling tired, forgetfulness, mood swings, restless or fidgety, and difficulty concentrating were associated with increased all-cause mortality. Moderate or severe dizziness had the largest HR (1.58 95% CI, 1.24-2.01). Multiple symptom modeling via least absolute shrinkage and selection operator selected dizziness, heart racing, feeling tired, and joint pain as most predictive of CVD, whereas dizziness, tremors, and feeling tired were most predictive of all-cause mortality. Among postmenopausal women with no known CVD at baseline, the severity of specific individual MS was significantly associated with incident CVD and mortality. Consideration of severe MS may enhance sex-specific CVD risk predication in future cohorts, but caution should be applied as severe MS could also indicate other health conditions.

Association between vitamin D and calcium intakes, breast microcalcifications, breast tissue age-related lobular involution and breast density.

To demystify the potential role of vitamin D and calcium intakes in breast carcinogenesis, we explored the association between these two nutrients and three biomarkers of breast cancer risk the presence of microcalcifications, age-related lobular involution and breast density. A total of 82 premenopausal and 79 postmenopausal women diagnosed with breast cancer completed a food frequency questionnaire to assess their total vitamin D and calcium intakes. Presence of microcalcifications was determined by reviewing pathology reports. Age-related lobular involution was assessed in nontumoral breast tissue on hematoxylin-eosin-stained slides and percent breast density was assessed by a computer-assisted method. Multivariate generalized linear models were used to evaluate associations between quartiles of vitamin D and calcium intakes and the biomarkers of breast cancer risk. Increasing quartiles of vitamin D intake were inversely associated with the presence of microcalcifications (fourth quartile Q4 prevalence ratio PR 0.55 Ptrend 0.021) and breast density (Q4-Q1 -7.7% Ptrend 0.023) in postmenopausal women, and positively associated with age-related lobular involution in women with microcalcifications (Q4 PR 1.62 Ptrend 0.036). Increasing quartiles of calcium intake were inversely associated with microcalcifications among all (Q4 PR 0.44), premenopausal (Q4 PR 0.37) and postmenopausal women (Q4 PR 0.38 Ptrend < 0.014 for all). It was also inversely associated with breast density in women without microcalcification (Q4-Q1 -8.3% Ptrend 0.047), but positively associated with breast density in women with microcalcifications (Q4-Q1 10.0% Ptrend 0.032). Results suggest that the association between vitamin D and calcium intakes and breast cancer risk factors could be influenced by the presence of microcalcifications.

Effects of Chicory and Fumitory on Hot Flashes Among Breast Cancer Survivors A Randomized, Double-Blind Placebo-Controlled Trial.

Iodinated Contrast Enhancement of Breast Cancer on Prone Multidetector Computed Tomography-Preliminary Findings.

Contrast-enhanced breast imaging has gained increasing importance in the diagnosis and management of breast cancer. The aim of this study was to assess breast cancer enhancement after contrast administration on prone multidetector computed tomography (MDCT). This retrospective, unicentric, institutional review board-approved study included patients with newly diagnosed breast cancer who were submitted to contrast-enhanced MDCT in prone position, with image acquisition before and after nonionic iodinated contrast administration. Sixty breast cancer patients aged between 31 and 74 years (mean, 49 years) were included. Most patients (n 50, 83.3%) had no special type invasive breast carcinoma and luminal subtype (n 45, 75%). All index breast tumors were identified on prone MDCT. Forty-three cases (70.5%) presented as mass, 13 (21.3%) as nonmass enhancement and 4 (6.6%) as both mass and nonmass enhancement. Mean tumor density was 37.8 HU and 87.9 HU on precontrast and postcontrast images, respectively. Mean contrast enhancement was 50.2 HU (range, 20-109 HU). There were no statistically significant differences in tumor enhancement according to histological type, molecular subtype, nuclear grade, tumor size, or imaging presentation. Our results show that breast cancer usually can be identified and have significant contrast enhancement on prone MDCT images. This method could be used as an alternative when other contrast-enhanced breast imaging methods are not available.

Attention-based Deep Learning for the Preoperative Differentiation of Axillary Lymph Node Metastasis in Breast Cancer on DCE-MRI.

Previous studies have explored the potential on radiomics features of primary breast cancer tumor to identify axillary lymph node (ALN) metastasis. However, the value of deep learning (DL) to identify ALN metastasis remains unclear. To investigate the potential of the proposed attention-based DL model for the preoperative differentiation of ALN metastasis in breast cancer on dynamic contrast-enhanced MRI (DCE-MRI). Retrospective. A total of 941 breast cancer patients who underwent DCE-MRI before surgery were included in the training (742 patients), internal test (83 patients), and external test (116 patients) cohorts. A 3.0 T MR scanner, DCE-MRI sequence. A DL model containing a 3D deep residual network (ResNet) architecture and a convolutional block attention module, named RCNet, was proposed for ALN metastasis identification. Three RCNet models were established based on the tumor, ALN, and combined tumor-ALN regions on the images. The performance of these models was compared with ResNet models, radiomics models, the Memorial Sloan-Kettering Cancer Center (MSKCC) model, and three radiologists (W.L., H.S., and F. L.). Dice similarity coefficient for breast tumor and ALN segmentation. Accuracy, sensitivity, specificity, intercorrelation and intracorrelation coefficients, area under the curve (AUC), and Delong test for ALN classification. The optimal RCNet model, that is, RCNet DCE-MRI-based RCNet model could provide a noninvasive auxiliary tool to identify ALN metastasis preoperatively in breast cancer, which may assist radiologists in conducting more accurate evaluation of ALN status. 3 TECHNICAL EFFICACY Stage 2.

A dedicated breast-PETCT scanner Numerical observer study of lesion detection.

Dedicated, breast-specific positron emission tomography (BPET)-cone-beam computed tomography (BPETCT) systems have been developed to improve detection and diagnosis of cancer in women with indeterminate mammograms caused by radiodense breasts. The absorption of X-rays that often vexes mammography in this subset of women does not affect the detection of the high energy annihilation photons used in PET. PET imaging of the breast, however, is subject to limitations caused by their comparatively low spatial resolution (∼2 mm) and often moderate radiotracer uptake in lesions. The purpose of this investigation is to explore the PET-based lesion detection capabilities of a BPETCT scanner developed by the Department of Radiology Instrumentation group at West Virginia University. The PET component of the system consists of a rotating pair of 96 × 72 arrays of 2 × 2 × 15 mm The results showed that the smallest detectable lesion with this system is no smaller than ∼3 mm in diameter with a TBR of 61. Simulated lesions with diameters of 4 mm and greater were calculated to have good to excellent likelihood of detection for all TBRs tested. The results from this investigation identified the detectability capabilities and limitations for a dedicated breast-PETCT scanner. Its ability to detect relatively small simulated FDG-avid breast lesions for a range of TBRs indicates its potential for clinical application. Finally, the study used methodologies that could be applied to a detectability assessment of other PETCT scanners.

Two fully automated data-driven 3D whole-breast segmentation strategies in MRI for MR-based breast density using image registration and U-Net with a focus on reproducibility.

Presence of higher breast density (BD) and persistence over time are risk factors for breast cancer. A quantitatively accurate and highly reproducible BD measure that relies on precise and reproducible whole-breast segmentation is desirable. In this study, we aimed to develop a highly reproducible and accurate whole-breast segmentation algorithm for the generation of reproducible BD measures. Three datasets of volunteers from two clinical trials were included. Breast MR images were acquired on 3 T Siemens Biograph mMR, Prisma, and Skyra using 3D Cartesian six-echo GRE sequences with a fat-water separation technique. Two whole-breast segmentation strategies, utilizing image registration and 3D U-Net, were developed. Manual segmentation was performed. A task-based analysis was performed a previously developed MR-based BD measure, MagDensity, was calculated and assessed using automated and manual segmentation. The mean squared error (MSE) and intraclass correlation coefficient (ICC) between MagDensity were evaluated using the manual segmentation as a reference. The test-retest reproducibility of MagDensity derived from different breast segmentation methods was assessed using the difference between the test and retest measures (Δ

Pharmacokinetics and Pharmacodynamics of PARP Inhibitors in Oncology.

Olaparib, niraparib, rucaparib, and talazoparib are poly (ADP-ribose) polymerase (PARP) inhibitors approved for the treatment of ovarian, breast, pancreatic, andor prostate cancer. Poly (ADP-ribose) polymerase inhibitors are potent inhibitors of the PARP enzymes with comparable half-maximal inhibitory concentrations in the nanomolar range. Olaparib and rucaparib are orally dosed twice a day, extensively metabolized by cytochrome P450 enzymes, and inhibitors of several enzymes and drug transporters with a high risk for drug-drug interactions. Niraparib and talazoparib are orally dosed once a day with a lower risk for niraparib and a minimal risk for talazoparib to cause drug-drug interactions. All four PARP inhibitors show moderate-to-high interindividual variability in plasma exposure. Higher exposure is associated with an increase in toxicity, mostly hematological toxicity. For talazoparib, exposure-efficacy relationships have been described, but for olaparib, niraparib, and rucaparib this relationship remains inconclusive. Further studies are required to investigate exposure-response relationships to improve dosing of PARP inhibitors, in which therapeutic drug monitoring could play an important role. In this review, we give an overview of the pharmacokinetic properties of the four PARP inhibitors, including considerations for patients with renal dysfunction or hepatic impairment, the effect of food, and drug-drug interactions. Furthermore, we focus on the pharmacodynamics and summarize the available exposure-efficacy and exposure-toxicity relationships.

A novel germline mutation of TP53 with breast cancer diagnosed as Li-Fraumeni syndrome.

TP53 is a tumor suppressor gene and, when dysfunctional, it is known to be involved in the development of cancers. Li-Fraumeni syndrome (LFS) is a hereditary tumor with autosomal dominant inheritance that develops in people with germline pathogenic variants of TP53. LFS frequently develops in parallel to tumors, including breast cancer. We describe a novel germline mutation in TP53 identified by performing a multi-gene panel assay in a breast cancer patient with bilateral breast cancer.

Breast Cancer Screening and Axillary Adenopathy in the Era of COVID-19 Vaccination.

A 50-year-old woman with persistent axillary lymphadenopathy 17 weeks after COVID-19 vaccination was ultimately diagnosed with biopsy-proven benign reactive lymphadenopathy. In contrast, a 60-year-old woman with axillary lymphadenopathy and concurrent suspicious breast findings 9 weeks after COVID-19 vaccination was ultimately diagnosed with biopsy-proven metastatic breast carcinoma. This article reviews the current guidelines regarding breast cancer screening and management of axillary lymphadenopathy in the setting of COVID-19 vaccination.

Relationship between Race and Access to Newer Mammographic Technology in Women with Medicare Insurance.

Background Racial disparities in breast cancer mortality have been reported. Mammographic technology has undergone two major technology transitions since 2000 first, the transition from screen-film mammography (SFM) to full-field digital mammography (FFDM) and second, the transition to digital breast tomosynthesis (DBT). Purpose To examine the relationship between use of newer mammographic technology and race in women receiving mammography services. Materials and Methods This was a multiyear (January 2005 to December 2020) retrospective study of women aged 40-89 years with Medicare fee-for-service insurance who underwent mammography. Data were obtained using a 5% research identifiable sample of all Medicare fee-for-service beneficiaries. Within-institution and comparable-institution use of mammographic technology between Black women or women of other races and White women were assessed with multivariable logistic and linear regression, respectively, adjusted for age, race, Charlson comorbidity index, per capita income, urbanicity, and institutional capability. Results Between 2005 and 2020, there were 4 028 696 institutional mammography claims for women (mean age, 72 years ± 8 SD). Within an institution, the odds ratio (OR) of Black women receiving digital mammography rather than SFM in 2005 was 0.80 (95% CI 0.70, 0.91

Evaluation of Seropositivity After Standard Doses of Vaccination Against SARS-CoV-2 in Patients With Early Breast Cancer Receiving Adjuvant Treatment.

Coronavirus disease 2019 (COVID-19) pandemic affected millions of individuals, and patients with cancer are known to be more susceptible. Vaccines against SARS-CoV-2 have been developed and used for patients with cancer, but scarce data are available on their efficacy in patients under active anti-cancer therapies. In this study, we semi-quantitatively measured the titers of the immunoglobulin G against the anti-spike protein subunit 1 of SARS-CoV-2 after vaccination of patients with early breast cancer undergoing concurrent chemotherapy, endocrinal or targeted non-cytotoxic treatments, and no treatments. Standard doses of COVID-19 vaccines provided sufficient immune responses in patients with early breast cancer, regardless of the type of anticancer therapies. However, the post-vaccination serum anti-spike antibody titers were significantly lower in the patients under cytotoxic chemotherapy. Our study emphasizes the importance of the personalized risk stratification and consideration for booster doses in more vulnerable populations.

Post-Remedial Oxygen Supply A New Perspective on Photodynamic Therapy to Suppress Tumor Metastasis.

Photodynamic therapy (PDT) holds great promise in tumor therapy due to high safety, efficacy, and specificity. However, the risk of increased metastasis in hypoxic tumors after oxygen-dependent PDT remains underestimated. Here, we propose a post-PDT oxygen supply (POS) strategy to reduce the risk of metastasis. Herein, biocompatible and tumor-targeting Ce6BSA and PFCBSA nanoparticles were constructed for PDT and POS in a 4T1-orthotropic breast cancer model. PDT with Ce6BSA nanoparticles increased tumor metastasis via the HIF-1α signaling pathway, whereas POS significantly reduced the PDT-triggered metastasis by blocking this pathway. Furthermore, POS, with clinical protocols and an FDA-approved photosensitizer (hypericin), and oxygen inhalation reduced PDT-induced metastasis. Our study findings indicate that PDT may increase the risk of tumor metastasis and that POS may solve this problem. POS can reduce the metastasis resulting not only from PDT but also from other oxygen-dependent treatments such as radiotherapy and sonodynamic therapy.

AIE-active Ir(III) complexes functionalised with a cationic Schiff base ligand synthesis, photophysical properties and applications in photodynamic therapy.

Photodynamic therapy (PDT) is a promising cancer treatment method. Traditional small-molecule photosensitizers (PSs) suffer from low intersystem crossing (ISC) ability and aggregation-caused quenching (ACQ), which adversely affects the luminous efficiency and singlet oxygen (

Photodynamic therapy in breast cancer treatment.

Breast cancer is a serious public problem in modern society. Photodynamic therapy (PDT) is increasingly used in modern medicine. Currently, PDT is an innovative method of treating breast cancer. Irreversible damage to neoplastic tissues is associated with the use of physicochemical processes. Generating cytotoxic reactive oxygen species singlet oxygen (1O2) is leading to tumor cell death. At the same time, valuable information can be extracted from breast cancer cells. Photogenerated 1O2 is the major factor responsible for cell necrosis during PDT. 1O2 can react rapidly intracellularly with all organic substances. The use of photodynamic therapy on tissues in vitro creates conditions for testing various types of solutions and implementing them in in vivo treatment. This article is a review of recent advances in PDT for treatment of breast cancer. PDT is a novel cancer diagnostic and cancer treatment therapy. Therefore, an understanding of the possibility to generate a toxic form of 1O2 is necessary. The knowledge gained from the basics of PDT in vitro can be useful in biomedical applications in vivo. The current literature mentions PDT in the treatment of cancers located very deep within the human body. Therefore, the development of agents used to deliver 1O2 to the deep cancerous tissue is a new challenge which can have an efficient impact on this discipline. This review covers the literature between 2000-2022.

Ubiquitin C-terminal hydrolase L1 (UCHL1), a double-edged sword in mammalian oocyte maturation and spermatogenesis.

Recent studies have shown that ubiquitin-mediated cell apoptosis can modulate protein interaction and involve in the progress of oocyte maturation and spermatogenesis. As one of the key regulators involved in ubiquitin signal, ubiquitin C-terminal hydrolase L1 (UCHL1) is considered a molecular marker associated with spermatogonia stem cells. However, the function of UCHL1 was wildly reported to regulate various bioecological processes, such as Parkinsons disease, lung cancer, breast cancer and colon cancer, how UCHL1 affects the mammalian reproductive system remains an open question. We identified papers through electronic searches of PubMed database from inception to July 2022. Here, we summarize the important function of UCHL1 in controlling mammalian oocyte development, regulating spermatogenesis and inhibiting polyspermy, and we posit the balance of UCHL1 was essential to maintaining reproductive cellular and tissue homeostasis. This study considers the double-edged sword role of UCHL1 during gametogenesis and presents new insights into UCHL1 in germ cells.

Validation of the modified Chinese Information and Support Needs Questionnaire (ISNQ-C) for daughters of mothers with breast cancer.

Adult daughters concerned about getting breast cancer throughout their lives and required support because their mothers had breast cancer. This article aims to examine the revised Information and Support Needs Questionnaire (ISNQ) and validate it in a Taiwanese community population comprising daughters of mothers with breast cancer. Using convenience sampling, daughters of mothers with breast cancer were recruited and were separated into 2 samples (Sample 1, Thirty-two items addressing 5 factors were identified for the ISNQ-C. Each factor had good internal consistency. The criterion validity was supported by significant correlations between the ISNQ-C scores and scores on the impacts of an event, anxiety, and depression. Known-group comparisons revealed that the group with deceased mothers reported significantly more unmet needs related to releasing my anxiety compared to the group where the mother was stable and undergoing regular follow-ups. The ISNQ-C demonstrated good reliability and validity in terms of assessing needs among daughters of mothers with breast cancer in Taiwan. Using this assessment tool before genetic counseling to target the individual needs of this population at risk for breast cancer would be helpful to provide personalized care.

Meta-Analysis of the Application Effect of Different Modalities of Thermal Ablation and Surgical Treatment in Papillary Thyroid Microcarcinoma.

Papillary thyroid microcarcinoma (PTMC) refers to papillary thyroid carcinoma (PTC) with a maximum diameter of 10 mm. Thermal ablation, including radiofrequency ablation (RFA), microwave ablation (MWA), and laser ablation (LA), has been applied in the treatment of benign thyroid nodules and captured extensive attention. At present, the application of thermal ablation in PTMC has been extensively reported, but outcomes such as volume reduction rate (VRR), complete remission rate (CRR), and adverse reaction rate (ARR) vary considerably. Therefore, this meta-analysis was performed to evaluate the safety and efficacy of different treatment methods of PTMC. We did a systematic review and network meta-analysis. We searched PubMed, EMBase, and Cochrane-Library from the date of inception to January 10, 2022, to retrieve the VRR, CRR, and ARR of MWA, RFA, LA and surgical treatment of PTMC, and a meta-analysis was performed using the R meta-package. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, and sensitivity analyses, cumulative meta-analyses, and publication bias were also performed. Relevant literature was retrieved with keywords the eligible cohort studies were screened based on the established inclusion and exclusion criteria. A total of 1515 patients were included in the 12-month follow-up. The overall VRR was 86.25% (95% CI 77.89, 94.60), and the VRR was RFA > WMA > LA, but the differences were not significant. A total of 1483 patients were included in the last follow-up. The overall VRR was 99.41% (95% CI 99.11, 99.72), and the VRR was RFA > WMA > LA, but the differences were not significant. A total of 1622 patients showed complete remission at the last follow-up, and the overall CRR was 0.63 (95% CI 0.46, 0.79). The CRR was RFA > LA > WMA, but the differences were not significant. A total of 1883 patients had adverse reactions at the last follow-up, and the overall ARR was 0.06 (95% CI 0.03, 0.08). The ARR at the last follow-up was RFA Surg < LA < WMA. The ARR of the RFA and Surg subgroups was significantly lower than that of the WMA subgroup. Similar good efficacy and safety profiles were observed in WMA, RFA, LA, and surgical treatment in PTMC, among which RFA showed the best volume reduction, complete remission rate, and adverse reaction reduction. However, there is a slight bias in the limited literature included in this study, and we did not conduct or refer to mechanistic studies to confirm its specific mechanism of action. Clinicians are advised to use their discretion in the choice of treatment.

Multicenter Randomized Open-Label Phase II Clinical Study Comparing Outcomes of NK105 and Paclitaxel in Advanced or Recurrent Breast Cancer.

NK105 is a paclitaxel (PTX)-incorporating core-shell-type polymeric micellar nanoparticle formulation composed of block copolymers (polyethylene glycol and a polyamino acid). The efficacy and safety of NK105 and paclitaxel in advanced or recurrent breast cancer have never been compared at equivalent dose levels. Patients were randomly assigned to either NK105 or PTX in a 11 ratio. The study drug was administered on Day 1, 8, and 15 of a 28-day cycle with 80 mgm A total of 123 patients (NK105, n62 PTX, n61) received one of the two drugs. There was no significant difference in ORR, the median PFS, or OS (NK105 group 41.9%, 9.1, and 27.5 months, respectively PTX group 45.9%, 7.8, and 32.4 months, respectively). Neutropenia occurred more frequently in the NK105 group, but most patients did not require granulocyte-colony stimulating factor or dose-reduction. The median time to onset of peripheral sensory neuropathy (PSN) in the NK105 group was significantly longer than that in the PTX group (p0.001), and PSN (≥ grade 3) was not observed in the NK105 group. Weekly NK105 administration was well-tolerated. Efficacy was similar in both groups. The PSN profile was better in the NK105 group.

High platelet-to-lymphocyte ratios in triple-negative breast cancer associates with immunosuppressive status of TILs.

Rating lymphocytes (TILs) are a prognostic marker in breast cancer and high TIL infiltration correlates with better patient outcomes. Meanwhile, parameters involving immune cells in peripheral blood have also been established as prognostic markers. High platelet-to-lymphocyte ratios (PLRs) and neutrophil-to-lymphocyte ratios (NLRs) are related to poor outcomes in breast cancer, but their mechanisms remain unknown. To date, TILs and these parameters have been examined separately. We investigated the relationship between TILs and the peripheral blood markers, PLR and NLR, in the same patients, using surgical specimens from 502 patients with invasive breast carcinoma without preoperative chemotherapy. For analysis of triple-negative breast cancer (TNBC) patient outcomes, 59 patients who received preoperative chemotherapy were also examined. For immune cell profiling, multiplexed fluorescent immunohistochemistry (mfIHC) of CD3, CD4, CD8, FOXP3 and T-bet, was conducted. A positive correlation between PLR and TIL was observed in TNBC (P 0.013). On mfIHC, tumors in patients with high PLR and NLR contained more CD3 Our data suggest that the combination of PLR with TIL assessment may enable more accurate prediction of patient outcomes with TNBC.

Colorectal cancer screening utilization among breast, cervical, prostate, skin, and lung cancer survivors.

To examine whether sociodemographic characteristics, access to care, risk behavior factors, and chronic health conditions were associated with colorectal cancer (CRC) screening utilization among breast, cervical, prostate, skin, and lung cancer survivors. We analyzed the 2020 Behavioral Risk Factor Surveillance System (BRFSS) data on 9780 eligible cancer survivors. Descriptive statistics and multivariable logistic regression models were applied to assess the association between guideline-concordant CRC screening and the mentioned characteristics. Overall, 81.9%, 65%, 88%,78.1%, and 80.1% of breast, cervical, prostate, skin, and lung cancer survivors received CRC screening, respectively (p-value < 0.001). In multivariable analysis, breast, cervical, and skin cancer survivors aged 60 years or older were associated with higher odds of receiving CRC screening. Respondents that had their recency of routine checkup two or more years before had lower odds of having CRC screening among cervical (OR 0.06 95% CI, 0.02-0.22), prostate (OR 0.26 95% CI, 0.14-0.49), and skin cancer (OR 0.50 95% CI, 0.36-0.70) survivors. The presence of chronic diseases was also associated with guideline-concordant CRC screening among breast, prostate, and skin cancer survivors. Our findings provide important evidence on potential factors that are associated with guideline-concordant CRC screening utilization across different cancer survivors, which include older age, recency of routine checkup, and multiple chronic diseases. Moreover, variation in CRC screening utilization across cancer survivors may highlight missed opportunities for secondary cancer prevention. Establishing clear CRC screening guidelines and including patient-provider communication on recommendation in cancer survivorship care may increase adherence to CRC screening.

Can We Forgo Sentinel Lymph Node Biopsy in Women Aged ≥ 50 Years with Early-Stage Hormone-Receptor-Positive HER2-Negative Special Histologic Subtype Breast Cancer

Breast cancer has significant biologic heterogeneity, which influences treatment decisions. We hypothesized that in postmenopausal women (≥ 50 years) with clinical T1-2, N0, hormone receptor positive (HR), HER2 negative (HER2-) breast cancer of special histology (mucinous, tubular, cribriform, papillary), information from sentinel lymph node biopsy (SLNB) may not change adjuvant therapy recommendations. We constructed a cohort from the National Cancer Database of women aged ≥ 18 years with cT1-2 N0 HR HER2- invasive breast cancer. We calculated the frequency of nodal positivity by histology. We measured the frequency of N2N3 disease, the distribution of Oncotype DX 21-gene assay recurrence score (ODX RS) across special histology by nodal status, and frequency of chemotherapy use by ODX RS and pathologic N stage. In women with cN0 HRHER2- special histologic subtype breast cancer, the likelihood of pathologic nodal positivity is less than 5%, and 99.7% of patients had N0 or N1 disease. Among women aged ≥ 50 years with HRHER2- special histologic subtype breast cancer, there was low prevalence of high ODX RS > 25 in both N0 and N1 patients (7% overall). Receipt of chemotherapy correlated with Oncotype DX scores as anticipated, with the lowest use in women with a lowintermediate RS (from 2 to 6% for N0 and 6-24% for N1) and the highest use in women with high risk Oncotype scores (from 74 to 92%). Our study suggests that SLNB could potentially be omitted in select postmenopausal women with cT1-2 N0 HRHER2- special histologic subtype breast cancer when ODX RS is available.

Autophagy (but not metabolism) is a key event in mitoxantrone-induced cytotoxicity in differentiated AC16 cardiac cells.

Mitoxantrone (MTX) is an antineoplastic agent used to treat advanced breast cancer, prostate cancer, acute leukemia, lymphoma and multiple sclerosis. Although it is known to cause cumulative dose-related cardiotoxicity, the underlying mechanisms are still poorly understood. This study aims to compare the cardiotoxicity of MTX and its pharmacologically active metabolite naphthoquinoxaline (NAPHT) in an in vitro cardiac model, human-differentiated AC16 cells, and determine the role of metabolism in the cardiotoxic effects. Concentration-dependent cytotoxicity was observed after MTX exposure, affecting mitochondrial function and lysosome uptake. On the other hand, the metabolite NAPHT only caused concentration-dependent cytotoxicity in the MTT reduction assay. When assessing the effect of different inhibitorsinducers of metabolism, it was observed that metyrapone (a cytochrome P450 inhibitor) and phenobarbital (a cytochrome P450 inducer) slightly increased MTX cytotoxicity, while 1-aminobenzotriazole (a suicide cytochrome P450 inhibitor) decreased fairly the MTX-triggered cytotoxicity in differentiated AC16 cells. When focusing in autophagy, the mTOR inhibitor rapamycin and the autophagy inhibitor 3-methyladenine exacerbated the cytotoxicity caused by MTX and NAPHT, while the autophagy blocker, chloroquine, partially reduced the cytotoxicity of MTX. In addition, we observed a decrease in p62, beclin-1, and ATG5 levels and an increase in LC3-II levels in MTX-incubated cells. In conclusion, in our in vitro model, neither metabolism nor exogenously given NAPHT are major contributors to MTX toxicity as seen by the residual influence of metabolism modulators used on the observed cytotoxicity and by NAPHTs low cytotoxicity profile. Conversely, autophagy is involved in MTX-induced cytotoxicity and MTX seems to act as an autophagy inducer, possibly through p62LC3-II involvement.

Quinoline-imidazolebenzimidazole derivatives as dual-multi-targeting hybrids inhibitors with anticancer and antimicrobial activity.

Two new classes of hybrid quinoline-imidazolebenzimidazole derivatives (the hybrid QIBS salts and QIBC cycloadducts) were designed and synthesized to evaluate their anticancer and antimicrobial activity. The strategy adopted for synthesis is straight and efficient, in four steps N-acylation, N-alkylation, quaternization and a Huisgen 3 2 cycloaddition. The in vitro single-dose anticancer assay of forty six hybrid quinoline-benzimidazole compounds reveal that one QIBS salt (11h), has an excellent quasi nonselective activity against all type of cancer cell with an excellent PGI in the area of 90-100% and very good lethality. Three others quinoline-imidazolebenzimidazole hybrids (8h, 12h, 12f) has an excellent selective activity against some cancer cell lines breast cancer MDA-MB-468 and Leukemia HL-60 TB). The five-dose assay screening confirms that compound 11h possesses excellent anti-proliferative activity, with GI

Reduced Survival Outcome After Receiving a New Cancer Diagnosis in the Emergency Department Findings from a Hospital Network in Rural Eastern North Carolina.

Patients whose cancer was found during an Emergency Department (ED) visit often present at later stages when survival outcomes are worse. Limited research has characterized the survival experience of cancer patients who receive their diagnosis through the ED versus those who do not. A retrospective cohort study identified all patients presenting to the ED between 2014 and 2015 in a rural, regional hospital system with a visit or resulting admission associated with an oncologic ICD-9 code. The chart was abstracted to determine a new cancer diagnosis versus an existing case. Cox proportional hazards (HR) estimated survival time. Patient and cancer characteristics were compared between those who were newly diagnosed through the ED and patients who were not. Thirty-nine percent of patients in our sample received their new cancer diagnosis as a result of an ED visit. The median survival was lower in cancer cases diagnosed through the ED (13 vs. 39 months, P < .001), men (20 vs. 32 months, P < .001), and patients aged ≥ 65 (22 months vs. 32 months, P < .001). Factors associated with lower survival were having a type of cancer location other than breast (HR 1.96 P < .001), followed by being newly diagnosed with cancer through the ED (HR 1.71 P < .001), and stage IV at diagnosis (HR 1.70 P < .001). Patients who received a new cancer diagnosis through the ED and required subsequent hospitalization had shorter overall survival and presented with advanced disease. Future research should address socioeconomic factors that may influence these patterns of cancer presentation.

Health effects associated with consumption of unprocessed red meat a Burden of Proof study.

Characterizing the potential health effects of exposure to risk factors such as red meat consumption is essential to inform health policy and practice. Previous meta-analyses evaluating the effects of red meat intake have generated mixed findings and do not formally assess evidence strength. Here, we conducted a systematic review and implemented a meta-regression-relaxing conventional log-linearity assumptions and incorporating between-study heterogeneity-to evaluate the relationships between unprocessed red meat consumption and six potential health outcomes. We found weak evidence of association between unprocessed red meat consumption and colorectal cancer, breast cancer, type 2 diabetes and ischemic heart disease. Moreover, we found no evidence of an association between unprocessed red meat and ischemic stroke or hemorrhagic stroke. We also found that while risk for the six outcomes in our analysis combined was minimized at 0 g unprocessed red meat intake per day, the 95% uncertainty interval that incorporated between-study heterogeneity was very wide from 0-200 g d

YTHDF2-mediated FGF14-AS2 decay promotes osteolytic metastasis of breast cancer by enhancing RUNX2 mRNA translation.

LncRNA FGF14-AS2 is a critical suppressor in breast cancer (BCa) metastasis. However, whether FGF14-AS2 plays a role in the bone metastasis of BCa remains unknown. TRAP assay and intratibial injection were carried out to evaluate the role of FGF14-AS2 in BCa bone metastasis in vitro and in vivo. Polyribosome profiling was done to examine the translation level. RNA pulldown combined with LCMS was performed to identify the lncRNA-binding partner, RIP, dual-luciferase assay, and Co-IP assays as well to testify these physical interactions. The prognostic value of FGF14-AS2 expression level in BCa patients was analysed using Kaplan-Meier Plotter. We found that FGF14-AS2 suppresses osteoclast differentiation and osteolytic metastasis of BCa. Mechanistically, FGF14-AS2 suppresses the translation of RUNX2 by inhibiting the assembly of eIF4EeIF4G complex and the phosphorylation of eIF4E, thereby reducing the transcription of RANKL, an essential regulator of osteoclast differentiation. Moreover, FGF14-AS2 is downregulated by YTHDF2-mediated RNA degradation in an m FGF14-AS2 plays a crucial role in osteolytic metastasis, and may serve as a promising prognostic biomarker and therapeutic target for BCa bone metastasis.

Elucidating tumor heterogeneity from spatially resolved transcriptomics data by multi-view graph collaborative learning.

Spatially resolved transcriptomics (SRT) technology enables us to gain novel insights into tissue architecture and cell development, especially in tumors. However, lacking computational exploitation of biological contexts and multi-view features severely hinders the elucidation of tissue heterogeneity. Here, we propose stMVC, a multi-view graph collaborative-learning model that integrates histology, gene expression, spatial location, and biological contexts in analyzing SRT data by attention. Specifically, stMVC adopting semi-supervised graph attention autoencoder separately learns view-specific representations of histological-similarity-graph or spatial-location-graph, and then simultaneously integrates two-view graphs for robust representations through attention under semi-supervision of biological contexts. stMVC outperforms other tools in detecting tissue structure, inferring trajectory relationships, and denoising on benchmark slices of human cortex. Particularly, stMVC identifies disease-related cell-states and their transition cell-states in breast cancer study, which are further validated by the functional and survival analysis of independent clinical data. Those results demonstrate clinical and prognostic applications from SRT data.

Smoking and Radiation-induced Skin Injury Analysis of a Multiracial, Multiethnic Prospective Clinical Trial.

Smoking during breast radiotherapy (RT) may be associated with radiation-induced skin injury (RISI). We aimed to determine if a urinary biomarker of tobacco smoke exposure is associated with increased rates of RISI during and after breast RT. Women with Stage 0-IIIA breast cancer treated with breast-conserving surgery or mastectomy followed by RT to the breast or chest wall with or without regional nodal irradiation were prospectively enrolled on a multicenter study assessing acutelate RISI. 980 patients with urinary cotinine (UCot) measurements (baseline and end-RT) were categorized into three groups. Acute and late RISI was assessed using the ONS Acute Skin Reaction scale and the LENT-SOMA Criteria. Late Grade 2 and Grade 3 RISI occurred in 18.2% and 1.9% of patients, respectively-primarily fibrosis, pain, edema, and hyperpigmentation. Grade 2 late RISI was associated with UCot group (P 006). Multivariable analysis identified UCot-based light smokersecondhand smoke exposure (HR 1.79, P .10) and smoking (HR 1.60, p .06) as non-significantly associated with an increased risk of late RISI. Hypofractionated breast RT was associated with decreased risk of late RISI (HR 0.51, P.03). UCot was not associated with acute RISI, multivariable analysis identified race, obesity, RT sitefractionation, and bra size to be associated with acute RISI. Tobacco exposure during breast RT may be associated with an increased risk of late RISI without an effect on acute toxicity. Smoking cessation should be encouraged prior to radiotherapy to minimize these and other ill effects of smoking.

NIR-II Excitation Phototheranostic Platform for Synergistic Photothermal TherapyChemotherapyChemodynamic Therapy of Breast Cancer Bone Metastases.

To improve bone metastases treatment efficacy, current strategies are focused on the integration of chemotherapy with phototheranostic. However, the success of phototheranostic approaches is hampered by the limited tissue penetration depth of near-infrared-I (NIR-I) light (700-900 nm). In this study, a NIR-II (1000-1700 nm) excitation phototheranostic (BTZFe

How cancer cells make and respond to interferon-I.

Acute exposure of cancer cells to high concentrations of type I interferon (IFN-I) drives growth arrest and apoptosis, whereas chronic exposure to low concentrations provides important prosurvival advantages. Tyrosine-phosphorylated IFN-stimulated gene (ISG) factor 3 (ISGF3) drives acute deleterious responses to IFN-I, whereas unphosphorylated (U-)ISGF3, lacking tyrosine phosphorylation, drives essential constitutive prosurvival mechanisms. Surprisingly, programmed cell death-ligand 1 (PD-L1), often expressed on the surfaces of tumor cells and well recognized for its importance in inactivating cytotoxic T cells, also has important cell-intrinsic protumor activities, including dampening acute responses to cytotoxic high levels of IFN-I and sustaining the expression of the low levels that benefit tumors. More thorough understanding of the newly recognized complex roles of IFN-I in cancer may lead to the identification of novel therapeutic strategies.

Association between COVID-19 incidence and postponement or cancellation of elective surgeries in Japan until September 2020 a cross-sectional, web-based survey.

This study aimed to examine whether and how the COVID-19 pandemic has affected the postponement or cancellation of elective surgeries in Japan. A cross-sectional, web-based, self-administered survey was conducted nationwide from August 25 to September 30 2020. We used data from the Japan COVID-19 and Society Internet Survey collected by a large internet research agency, Rakuten Insight, which had approximately 2.2 million qualified panellists in 2019. From a volunteer sample of 28 000 participants, we extracted data from 3678 participants with planned elective surgeries on any postponement or cancellation of elective surgeries. The main outcome measure was any postponement or cancelltion of elective surgeries. In addition, for all respondents, we extracted data on sociodemographic, health-related characteristics, psychological characteristics and prefectural-level residential areas. We used weighted logistic regression approaches to fulfil the study objectives, minimising potential bias relating to web-based surveys. Of the 3678 participants, 431 (11.72%) reported experiencing postponement or cancellation of their elective surgeries. Notably, the participants living in prefectures where the declaration of the state of emergency was made on 7 April 2020 were significantly more likely to experience postponement or cancellation of elective surgeries than those residing in prefectures with the state of emergency beginning on 16 April 2020 (174 (26.02%) vs 153 (12.15%)). The proportion of patients whose elective surgery had been postponed was limited during Japans first wave of the COVID-19 pandemic, although the declaration of a state of emergency increased the likelihood of postponement. It is imperative to increase awareness of the secondary health effects related to policy intervention in pandemics and other health crises and to use appropriate countermeasures such as standard infectious control measures and triage of surgical patients.

Optimizing Preventive Adjuvant Linac-Based (OPAL) Radiation A Phase 2 Trial of Daily Partial Breast Irradiation.

Evidence supports use of partial-breast irradiation (PBI) in the management of early breast cancer, but the optimal dose-fractionation remains unsettled. We conducted a phase 2 clinical trial (OPAL trial) to evaluate a novel PBI dosing schedule of 35 Gy in 10 daily fractions. Patients with close (<2 mm) margins also received a boost of 9 Gy in 3 fractions. Eligible patients underwent margin-negative lumpectomy for ductal carcinoma in situ or estrogen receptor-positive invasive breast cancer, up to 3 cm, pTis-T2 N0. The primary outcome was any grade ≥2 toxic effect occurring from the start of radiation through 6 months of follow-up. Secondary outcomes included patient-reported cosmesis, breast pain, and functional status, measured using the Breast Cancer Treatment Outcomes Scale, and physician-reported cosmesis, measured using the Radiation Therapy and Oncology Group scale. The Cochran-Armitage trend test and multivariable mixed-effects longitudinal growth curve models compared outcomes for the OPAL study population with those for a control group of similar patients treated with whole-breast irradiation (WBI) plus boost. All 149 patients enrolled on the OPAL trial received the prescribed dose, and 17.4% received boost. The median age was 64 years 83.2% were White, and 73.8% were overweight or obese. With median follow-up of 2.0 years, 1 patient (0.7%) experienced in-breast recurrence. Prevalence of the primary toxicity outcome was 17.4% (26 of 149 patients) in the OPAL trial compared with 72.7% (128 of 176 patients) in the control WBI-plus-boost cohort (P < .001). In longitudinal multivariable analysis, treatment on the OPAL trial was associated with improved patient-reported cosmesis (P < .001), functional status (P .004), breast pain (P .004), and physician-reported cosmesis (P < .001). Treatment with daily PBI was associated with substantial reduction in early toxicity and improved patient- and physician-reported outcomes compared with WBI plus boost. Daily external-beam partial-breast irradiation with 13 or fewer fractions merits further prospective evaluation.

Radiotherapy activity in the COVID 19 pandemic Brazils operational national-level study.

During the COVID-19 pandemic, patients with cancer are at increased risk of not having timely diagnosis and access to cancer treatment. The present study evaluated the COVID-19 pandemic impact on radiotherapy activity in Brazil. A national-level study was performed to evaluate the RT utilization for prostate, breast, head neck (HN), Gynecology (GYN), Gastrointestinal (GI), lung cancers, and bonebrain metastases. The data on the RT executed was extracted from the Brazilian Ministry of Health database. The NON-COVID period was considered the control group, and the comparison groups were COVID-2020 (without vaccine) and COVID-2021 (with vaccine). We collected the data of 238,355 procedures executed on three periods. Significant difference in the RT utilization between NON-COVID and COVID-2020 were observed for prostate cancer, bone and brain metastases (-12.3%, p0.02, 24%, p0.02 and 14%, p0.04, respectively). Comparing 2 equivalents months from NON-COVID-2019 (ref), COVID-2020, and COVID-2021, a significant increase was identified for bone and brain metastases (2020 21%, and 2021 32%), and (2020 20%, and 2021 14%). A stable drop occurred for prostate cancer (2020 -11% and 2021 -10%), and a variation was observed for breast (2020 8%, and 2021 -1%) and lung cancer (2020 10%, and 2021 -3%). For other cancers, non-significant changes were observed when comparing 2020 and 2021. The RT activity was heterogeneously affected with a substantial increase for bone and brain metastases and a meaningful decline for prostate cancer. With a significant increase in the use of palliative radiotherapy for bone and brain metastases and a meaningful reduction in curative radiotherapy for prostate cancer, we hope these findings can help governments, RT services, medical communities, and other stakeholders develop strategies to mitigate the impact of the present and future pandemics. Finally, despite the changes imposed by the COVID pandemic, it is imperative to enhance screening, increase cancer diagnosis at an early stage, and improve access to all cancer treatments, including radiotherapy.

ERK activation modulates invasiveness and Reactive Oxygen Species (ROS) production in triple negative breast cancer cell lines.

Triple negative breast cancer (TNBC) is the breast cancer subtype with the worst prognosis and still lacks a targeted therapy. In this study, we found increased ERK phosphorylation in TNBC cell lines and an important role for ERK in sustaining the migration of TNBC cells. Although ROS have been suggested to have an important role in sustaining MAPK signaling, antioxidant treatment increased ERK phosphorylation, probably suggesting increased invasive potential. Interestingly, treatment with PD0325901 (PD), a MEK inhibitor, decreased ROS levels in TNBC cells and decreased mitochondrial fragmentation in the MDAMB231 cell line. Our data supports an important role for MEKERK in TNBC, sustaining cellular migration, regulating mitochondrial dynamics and ROS production in this breast cancer subtype.

CD55 in cancer Complementing functions in a non-canonical manner.

CD55, or decay accelerating factor, is a membrane lipid microdomain-associated, GPI-anchored protein implicated in the shielding of cells from complement-mediated attack via accelerating decay of C3 and C5. Loss of CD55 is associated with a number of pathologies due to hyperactivation of the complement system. CD55 is also implicated in cancer progression thought to be driven via its role in cell shielding mechanisms. We now appreciate that CD55 can signal intracellularly to promote malignant transformation, cancer progression, cell survival, angiogenesis, and inhibition of apoptosis. Outside-in signaling via CD55 is mediated by signaling pathways including JNK, JAKSTAT, MAPKNF-κB, and LCK. Moreover, CD55 is enriched in the cancer stem cell (CSC) niche of multiple tumors including breast, ovarian, cervical, and can be induced by chemotherapeutics and hypoxic environments. CSCs are implicated in tumor recurrence and chemoresistance. Here, we review the unexpected roles of CD55 in cancer including the roles of canonical and noncanonical pathways that CD55 orchestrates. We will highlight opportunities for therapeutic targeting CD55 and gaps in the field that require more in-depth mechanistic insights.

Coverage rate of opportunistic and organised breast cancer screening in France Department-level estimation.

In France, the national breast cancer screening programme (NBCSP), targeting women aged 50-74 years was rolled out nationwide in 2004. It aims at reducing breast cancer mortality. In addition to the NBCSP, the use of opportunistic screening is permitted in France. The objective of this study is to estimate both opportunistic use and overall coverage rates of breast cancer screening, among women 40-84 years of age, in France. The French medico-administrative health data system (SNDS) was used to identify women performing an opportunistic or organised mammography screening in France in 2016-2017. The two-yearly opportunistic mammography screening is 18 % among women aged 40-84 it is 11 % among women aged 50-74, i.e., the target age range for organised screening, 36 % among women aged 40-49 and 13 % among women aged 75-84. The overall two-yearly screening coverage is 48 % for all women aged 40-84 it is 60 % among women aged 50-74, 36 % among women 40-49 and 16 % for those aged 75-84. Geographical variations in screening are lessened when the two screening strategies are considered, as they balance each other. Although coverage in the NBCSP is around 50 % in France, more than one third of the women make use of opportunistic screening within and outside the target age range. Organized screening appears to improve equity of access to mammography screening service. The lack of data on opportunistic screening practices hinders the evaluation of French screening practices as a whole.

Modality-correlation embedding model for breast tumor diagnosis with mammography and ultrasound images.

The fusion of mammography and ultrasound images helps to improve tumor classification accuracy. However, traditional fusion models ignore the correlation between these two modalities, resulting in limited performance improvement. To address this problem, a modality-correlation embedding model was proposed for breast tumor diagnosis by combining mammography and ultrasound imaging. By jointly optimizing the correlation between mammography and ultrasound and classification loss of individual modalities, two mappings are learned to project mammography and ultrasound from their original feature spaces into a common label space. A novel modality-correlation term is introduced to maintain the pairwise closeness of multimodal data in the common label space. Contrary to previous studies that did not consider the correlation between multimodal data, the proposed term can exploit the learned correlation information in the fusion process, which guarantees the consistency of the diagnosis results of multimodal images from the same patient. The proposed method was evaluated on our dataset, which contained ultrasound and mammography images from 73 patients. The area under the ROC curve, accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 95.83, 95, 91.67, 95.83, 95.83, and 88.89%, respectively. The experimental results also demonstrate that the proposed method outperforms traditional fusion methods.

Experience of the Hybrid technique for breast cancer planning in an oncology care center in Lima-Peru.

To investigate, describe and evaluate the dosimetric parameters of the hybrid technique as a combination of the 3D Irregular Surface Compensator (3D-ISC) technique and modulated volumetric arc therapy (VMAT) for breast cancer planning. The study involved planning a patient with left breast cancer. Planning was carried out with 3D-ISC, VMAT and Hybrid techniques. The 3 techniques were compared with respect to the target volume (PTV), coverage, gradient and protection of organs at risk (OARs). The Eclipse version 13.6 planning system was used and the prescription of the dose obeyed the hypofractionated scheme of 40.05Gy in 15 sessions (267 cGy per fraction) followed by a 13.35Gy boost in 5 sessions. The tangential field technique was the one with the lowest dose values delivered to healthy organs. However, with respect to the gradient, the VMAT technique was better. The Hybrid technique was the balance between the 3D-ISC and VMAT technique because after the evaluation of dosimetric parameters for both the OARs and the PTV coverage, values were found within the limits allowed according to the RTOG. The hybrid 3D-ISC and VMAT technique can be considered as a viable option for breast planning, achieving better control in OARs without losing priority over PTV coverage in addition to obtaining a good plan quality.

Exploring Bias in Scientific Peer Review An ASCO Initiative.

To investigate implicit bias (IB) in the peer review process across ASCO and Conquer Cancer Foundation and to propose potential mitigation strategies. We, ASCO Working Group on Implicit Bias, selected four data sources (1) literature search (a) defining IB in peer review, (b) evidence of IB in peer review, and (c) strategies to mitigate IB (2) created and analyzed an ASCO database for sex, race, and institutional affiliation regarding peer review success (3) constructed and conducted qualitative interviews of key stakeholders within the ASCO board, publications, and grants committee, on experience with IB within ASCO and (4) constructed, delivered, and analyzed results of member survey on perception of IB within ASCO. Historically uncommon, PubMed articles on IB in peer review subsequently increased exponentially in the past 2 decades. Qualitative interviews of ASCO key stakeholders reveal that system changes and IB training were priorities. The committee member survey reported that their peer review decisions could be affected by IB and that mitigating IB should be a priority. Most reported having never been trained on IB. Available data from ASCO database support stakeholder findings, suggesting that there exists a disproportionate representation of males and better-known institutions among both reviewer positions and awardees. Ethnicityrace data were insufficiently reported. Limited data on interventionsstrategies to mitigate IB in the peer-reviewed literature suggest that there are feasible processes for grants, program committees, and journals. Limited data reveal that the peer review process at ASCO is not exempt from IB and suggest association with sex and institutional affiliation. Working Group on Implicit Bias recommends three actions to mitigate IB within peer review (1) create awareness and a culture of inclusivity, (2) create systems to reduce IB, and (3) collect data for ongoing analysis.

Development of an Electronic Health Record Registry to Facilitate Collection of Commission on Cancer Metrics for Patients Undergoing Surgery for Breast Cancer.

Accurate and efficient data collection is a challenge for quality improvement initiatives and clinical research. We describe the development of a custom electronic health record (EHR)-based registry to automatically extract structured Commission on Cancer axillary surgery-specific metrics from a custom synoptic note template included in the operative reports for patients with breast cancer undergoing surgery. The smart functionality of our enterprise-based EHR system was leveraged to create a custom smart phrase to capture axillary surgery-specific variables. A multidisciplinary team developed structured data elements correlating to each axillary surgery-specific variable. These data elements were then included in a note template for the operative report. Each variable could be aggregated and converted into a single flat database through the EHRs reporting workbench and serve as a live, prospective registry for all users within the EHR. The final axillary surgery-specific note template in a synoptic format allowed for efficient and easy entry and automatic collection of breast cancer-specific metrics. From initial adoption in February 2021-December 2021, there were 1,254 patients who underwent breast surgery with axillary surgery. The operative notes allowed for automatic capture of metrics from 60.5% (n 759) of patients. Data capture improved from 37.6% in the initial adoption period of 6 months to 86.2% in the last 5 months. We were able to demonstrate successful implementation of provider-driven structured data entry into EHR systems that permits automatic data capture. The end result is a custom synoptic note template and a real-time, prospective registry of breast cancer-specific Commission on Cancer metrics that are robust enough to use for quality improvement initiatives and clinical research.

Cinobufagin inhibits proliferation and induces apoptosis of hepatocarcinoma cells by activating apoptosis, AKT, and ERK pathways.

Cinobufagin is one of the pharmaceutically active ingredients in the parotoid glands of the Chinese toad Bufo bufo gargarizans Cantor. This study was conducted to investigate the effect of cinobufagin on viability, migration, and apoptosis of hepatocellular carcinoma (HCC) cells and its mechanisms. Human HCC cells (HepG2) were treated with cinobufagin and assessed for viability, apoptosis, and migration using CCK-8 assay, flow cytometry, and wound healing assay. The expression of genes related to the p53, AKT, and ERK pathways was detected using RT-PCR and Western blot analysis. Cell viability assays showed that cinobufagin reduced the viability of HepG2 cells in a concentration- and time-dependent manner. Significantly increased apoptosis was detected in cinobufagin-treated cells as compared with non-treated cells. The migration ability of HepG2 cells was significantly reduced after they were exposed to cinobufagin as compared with control. RT-PCR and Western blot analyses showed that the expression levels of p53, caspase-3, and Bax were significantly upregulated, and the expression levels of AKT and ERK were significantly downregulated after cinobufagin treatment. Our data demonstrated that cinobufagin reduces the viability and induces apoptosis of HepG2 cells. The cytotoxicity is likely achieved by upregulating the p53 pathway and downregulating the Akt and ERK pathways.

Bip-Yorkie interaction determines oncogenic and tumor-suppressive roles of Ire1Xbp1s activation.

Unfolded protein response (UPR) is the mechanism by which cells control endoplasmic reticulum (ER) protein homeostasis. ER proteostasis is essential to adapt to cell proliferation and regeneration in development and tumorigenesis, but mechanisms linking UPR, growth control, and cancer progression remain unclear. Here, we report that the Ire1Xbp1s pathway has surprisingly oncogenic and tumor-suppressive roles in a context-dependent manner. Activation of Ire1Xbp1s up-regulates their downstream target Bip, which sequesters Yorkie (Yki), a Hippo pathway transducer, in the cytoplasm to restrict Yki transcriptional output. This regulation provides an endogenous defensive mechanism in organ size control, intestinal homeostasis, and regeneration. Unexpectedly,

Clinical Outcomes of Metastatic Breast Cancer in Patients Having Imaging Liver Pseudocirrhosis with or without Evident Varices.

Pseudocirrhosis is an imaging finding of malignancies with liver metastasis with or without clinical liver cirrhosis-related portal hypertension (pHTN). This study defined evident pHTN by the presence of esophageal or gastric varices and compared patients outcomes of metastatic breast cancer with imaging-diagnosed pseudocirrhosis with or without varices. The medical records from patients with metastatic breast cancer and pseudocirrhosis between 2005 and 2017 were retrospectively analyzed. Survival outcomes were compared based on endoscopic evidence of esophageal or gastric varices. Among 106 patients with pseudocirrhosis, 33 (31%) had de novo stage IV disease, and 66 (62%) had hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Eighty-one (76%) had initial metastases in both hepatic lobes, and 32 (30%) had esophageal or gastric varices. The median overall survival (OS) was 5 and 13 months in patients with and without varices (P .002). The median OS in patients with HER2-positive, HR-positiveHER2-negative, and triple-negative subtype was 16, 9, and 2 months, respectively (P .001). Patients with varices usually had cirrhotic complications, including gastrointestinal bleeding, hyperbilirubinemia, hyperammonemia, and coagulopathy. Despite their challenging clinical conditions, 7 patients with varices had OS exceeding 1 year. In multivariate analysis, evident varices (P .007) and triple-negative subtype (P .013) were associated with poor OS. Patients with pseudocirrhosis and evident varices had a significantly shorter median OS, and were usually associated with clinical cirrhosis-related complications. To maximize OS, early identification and meticulous supportive care are warranted.

Breast Cancer Incidence in Relation to Long-Term Low-Level Exposure to Air Pollution in the ELAPSE Pooled Cohort.

Established risk factors for breast cancer include genetic disposition, reproductive factors, hormone therapy, and lifestyle-related factors such as alcohol consumption, physical inactivity, smoking, and obesity. More recently a role of environmental exposures, including air pollution, has also been suggested. The aim of this study, was to investigate the relationship between long-term air pollution exposure and breast cancer incidence. We conducted a pooled analysis among six European cohorts (n 199,719) on the association between long-term residential levels of ambient nitrogen dioxide (NO2), fine particles (PM2.5), black carbon (BC), and ozone in the warm season (O3) and breast cancer incidence in women. The selected cohorts represented the lower range of air pollutant concentrations in Europe. We applied Cox proportional hazards models adjusting for potential confounders at the individual and area-level. During 3,592,885 person-years of follow-up, we observed a total of 9,659 incident breast cancer cases. The results of the fully adjusted linear analyses showed a HR (95% confidence interval) of 1.03 (1.00-1.06) per 10 μgm³ NO2, 1.06 (1.01-1.11) per 5 μgm³ PM2.5, 1.03 (0.99-1.06) per 0.5 10-5 m-1 BC, and 0.98 (0.94-1.01) per 10 μgm³ O3. The effect estimates were most pronounced in the group of middle-aged women (50-54 years) and among never smokers. The results were in support of an association between especially PM2.5 and breast cancer. The findings of this study suggest a role of exposure to NO2, PM2.5, and BC in development of breast cancer.

Validation of the Nigerian Breast Cancer Study Model for Predicting Individual Breast Cancer Risk in Cameroon and Uganda.

The Nigerian Breast Cancer Study (NBCS) model is a new risk assessment tool developed for predicting risk of invasive breast cancer in Nigeria. Its applicability outside of Nigeria remains uncertain as it has not been validated in other sub-Saharan Africa populations. We conducted a case-control study among women with breast cancer and controls ascertained in Cameroon and Uganda from 2011 to 2016. Structured questionnaire interviews were performed to collect risk factor characteristics. The NBCS model, the Gail model, the Gail model for Black population, and the Black Womens Health Study model were applied to the Cameroon and Uganda samples separately. Nigerian as well as local incidence rates were incorporated into the models. Receiver-Operating Characteristic analyses were performed to indicate discriminating capacity. The study included 550 cases (mean age 46.8 ± 11.9) and 509 controls (mean age 46.3 ± 11.7). Compared with the other three models, the NBCS model performed best in both countries. The discriminating accuracy of the NBCS model in Cameroon (age-adjusted C-index 0.602 95% CI, 0.542-0.661) was better than in Uganda (age-adjusted C-index 0.531 95% CI, 0.459-0.603). These findings demonstrate the potential clinical utility of the NBCS model for risk assessment in Cameroon. All currently available models performed poorly in Uganda, which suggests that the NBCS model may need further calibration before use in other regions of Africa. Differences in risk profiles across the African diaspora underscores the need for larger studies and may require development of region-specific risk assessment tools for breast cancer.

Clinical Efficacy and Whole-Exome Sequencing of Liquid Biopsies in a Phase IBII Study of Bazedoxifene and Palbociclib in Advanced Hormone Receptor-Positive Breast Cancer.

Sensitivity to endocrine therapy (ET) is critical for the clinical benefit from the combination of palbociclib plus ET in hormone receptor-positiveHER2-negative (HRHER2-) advanced breast cancer. Bazedoxifene is a third-generation selective estrogen receptor (ER) modulator and selective ER degrader with activity in preclinical models of endocrine-resistant breast cancer, including models harboring ESR1 mutations. Clinical trials in healthy women showed that bazedoxifene is well tolerated. We conducted a phase IbII study of bazedoxifene plus palbociclib in patients with HRHER2- advanced breast cancer who progressed on prior ET (N 36 NCT02448771). The study met its primary endpoint, with a clinical benefit rate of 33.3%, and the safety profile was consistent with what has previously been seen with palbociclib monotherapy. The median progression-free survival (PFS) was 3.6 months 95% confidence interval (CI), 2.0-7.2. An activating PIK3CA mutation at baseline was associated with a shorter PFS (HR 4.4 95% CI, 1.5-13 P 0.0026), but activating ESR1 mutations did not impact the PFS. Longitudinal plasma circulating tumor DNA whole-exome sequencing (WES N 68 plasma samples) provided an overview of the tumor heterogeneity and the subclonal genetic evolution, and identified actionable mutations acquired during treatment. The combination of palbociclib and bazedoxifene has clinical efficacy and an acceptable safety profile in a heavily pretreated patient population with advanced HRHER2- breast cancer. These results merit continued investigation of bazedoxifene in breast cancer.

Physician Perspectives on Reducing Curative Cancer Treatment Intensity for Populations Underrepresented in Clinical Trials.

Historically, clinical trials involved adding novel agents to standard of care to improve survival. There has been a shift to an individualized approach with testing less intense treatment, particularly in breast cancer where risk of recurrence is low. Little is known about physician perspectives on delivering less intense treatment for patients who are not well represented in clinical trials. Open-ended, individual qualitative interviews with medical oncologists explored their perspectives on trials that test less intense treatment for patients with cancer, with a focus on breast cancer. Interviews were audio-recorded and transcribed. Four independent coders utilized a content analysis approach to analyze transcripts using NVivo. Major themes and exemplary quotes were extracted. Of the 39 participating physicians, 61.5% felt comfortable extrapolating, 30.8% were hesitant, and 7.7% would not feel comfortable extrapolating trial outcomes to underrepresented populations. Facilitators of comfort included the sentiment that biology is biology (such that the cancer characteristics were what mattered), the strength of the evidence, inclusion of subset analysis on underrepresented populations, and prior experience making decisions with limited data. Barriers to extrapolation included potential harm over the patients lifetime, concerns about groups that had minimal participants, application to younger patients, and extending findings to diverse populations. Universally, broader inclusion in trials testing lowering chemotherapy was desired. The majority (92%) of physicians reported that they would de-implement treatment for patients poorly represented in clinical trials testing less treatment, while expressing concerns about applicability to specific subpopulations. Further work is needed to increase clinical trial representation of diverse populations to safely and effectively optimize treatment for patients with cancer. NCT03248258.

Designing a novel SOX9 based multi-epitope vaccine to combat metastatic triple-negative breast cancer using immunoinformatics approach.

Immunotherapies are a promising treatment option especially for the management of TNBC owing to its higher levels of tumour-associated antigens together with higher mutational load. Of note, the administration of preventive vaccines in the early stage of the cancer holds promise for effective disease management. Therefore, the present study aimed to develop a novel multi-epitope peptide-based vaccination against TNBC employing SOX9, which has recently been recognized as a key regulator of TNBC metastasis. The immunodominant regions from the SOX9 protein were computed and assessed based on their ability to elicit both T and B lymphocyte mediated responses. The resultant epitopes were fused using appropriate linkers (EAAAK, KK, AAY and GPGPG) and adjuvant (50S ribosomal protein L7L12) to enhance the vaccines immunogenicity. The physicochemical properties and population coverage were also anticipated for the constructed vaccine. Adding together, docking and dynamics simulation studies were performed on the modelled vaccine against TLR-4 to provide insight into the stability. Finally, the designed vaccine was cloned into the pET28 () vector and immunological simulation studies were carried out. These results demonstrate that our designed vaccine had the potency to trigger humoral and cellular immune responses. Based on these collective evidences, the final proposed vaccine could be an interesting therapeutics for the management of TNBC in the near future. Schematic representation of an efficient vaccine design framework by combining the range of immunoinformatics strategies.

Antiproliferative Activity of Green Synthesised Silver Nanoparticles of Cassia Marginata Roxb.

Green synthesised silver nanoparticles (AgNPs) have been identified as a promising new therapy pathway for cancer because of their anti-angiogenic potency. In the present study, CM-AgNPs were biosynthesized using aqueous leaf extract of Cassia marginata Roxb (CM) and were confirmed by spectral studies like UV-Visible and attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopic techniques. The structure and shape of the biosynthesized CM-AgNPs were confirmed by scanning electron microscope (SEM), energy-dispersive spectroscopy (EDX), and high-resolution transmission electron microscopy (HR-TEM) with selected area electron diffraction (SAED) studies. The antioxidant activity of the synthesized nanoparticles were evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assay methods, and the IC

Current trends in diagnostic and therapeutic management of the axilla in breast cancer patients receiving neoadjuvant therapy results of the German-wide NOGGO MONITOR 24 survey.

In the last 2 decades, the optimal management of the axilla in breast cancer patients receiving neoadjuvant chemotherapy (NACT) has been one of the most frequently discussed topics. Little is known about the attitudes of surgeonsradiologists towards new developments such as targeted axillary dissection. Therefore, the NOGGO conducted a survey to evaluate the current approach to axillary management. A standardized digital questionnaire was sent out to > 200 departments in Germany between 72021 and 52022. The survey was supported by EUBREAST. In total, 116 physicians completed the survey. In cN0 patients scheduled to receive NACT, 89% of respondents recommended sentinel lymph node biopsy (SLNB) after NACT. In case of ypN1mi(sn), 44% advised no further therapy, while 31% proposed ALND and 25% axillary irradiation. 64% of respondents recommended a minimally invasive axillary biopsy to cN patients. TAD was used at the departments of 82% of respondents and was offered to all cN patients converting to ycN0 by 57% and only to selected patients, usually based on the number of suspicious nodes at time of presentation, by 43%. The most common marking technique was a clipcoil. 67% estimated that the detection rate of their marker was very good or good. This survey shows a heterogenous approach towards axillary management in the neoadjuvant setting in Germany. Most respondents follow current guidelines. Since only two-thirds of respondents experienced the detection rate of the marker used at their department as (very) good, future studies should focus on the comparative evaluation of different marking techniques.

A global survey on the utilization of cryotherapy and compression therapy for the prevention of chemotherapy-induced peripheral neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect that is highly prevalent among cancer patients undergoing chemotherapy. There is a growing use of cryotherapy (CryTx) and compression therapy (ComTx) to prevent CIPN at cancer centers worldwide. In this study, we examined the awareness and recommendation of these modalities and evaluated factors associated with awareness. In addition, we investigated the type of technology utilized, barriers to implementation, and perceived adverse events of CryTx and ComTx. Active members of the Multinational Association of Supportive Care of Cancer (MASCC) were invited to complete an electronic survey that was sent via SurveyMonkey between September and October 2021. The survey assessed participants awareness, recommendation, usage, barriers to utilization, and perceived adverse events of CryTx and ComTx. Descriptive statistics and multiple logistic regression were utilized to analyze findings. Out of 184 participants, 70.1% were physicians, 73.4% had over 10 years of practice, and 49.5% were practicing in an outpatient setting. While more than half (63.3%) of participants indicated awareness of CryTx for taxane-induced peripheral neuropathy, less than a quarter (22.8%) indicated recommendation in their practice setting. Factors associated with higher awareness of CryTx for patients receiving taxanes include living in Europe (OR 2.69, 95% CI 1.28-5.64, p 0.009), not practicing in an inpatient setting (OR 3.15, 95% CI 1.45-6.85, p 0.004), and self-identifying as non-physician (OR 2.40, 95% CI 1.03-4.37, p 0.041). Commercial cooling (31.5%) and compression (16.8%) gloves and socks were the most used modalities for CryTx and ComTx, respectively. The most identified barriers to CryTx and ComTx utilization include insufficient evidence (53.5%), logistics (34.8%), and patient discomfort (23.4%). Rednessirritation of skin (27.7%) and numbnesstingling (24.5%) accounted for about half of the perceived adverse events associated with use of CryTx and ComTx. Results of our global survey illustrated that there are varying modes in the delivery of CryTx and ComTx among cancer centers around the world. Education of the utilization of CryTx and ComTx, in addition to efficacy and implementation studies, is needed to close the gap between awareness and implementation in clinical practice.

Proteomic signature for detection of high-grade ovarian cancer in germline BRCA mutation carriers.

No current screening methods for high-grade ovarian cancer (HGOC) guarantee effective early detection for high-risk women such as germline BRCA mutation carriers. Therefore, the standard-of-care remains risk-reducing salpingo-oophorectomy (RRSO) around age 40. Proximal liquid biopsy is a promising source of biomarkers, but sensitivity has not yet qualified for clinical implementation. We aimed to develop a proteomic assay based on proximal liquid biopsy, as a decision support tool for monitoring high-risk population. Ninety Israeli BRCA1 or BRCA2 mutation carriers were included in the training set (17 HGOC patients and 73 asymptomatic women), (BEDOCA trial ClinicalTrials.gov Identifier NCT03150121). The proteome of the microvesicle fraction of the samples was profiled by mass spectrometry and a classifier was developed using logistic regression. An independent cohort of 98 BRCA mutation carriers was used for validation. Safety information was collected for all women who opted for uterine lavage in a clinic setting. We present a 7-protein diagnostic signature, with AUC >0.97 and a negative predictive value (NPV) of 100% for detecting HGOC. The AUC of the biomarker in the independent validation set was >0.94 and the NPV >99%. The sampling procedure was clinically acceptable, with favorable pain scores and safety. We conclude that the acquisition of Müllerian tract proximal liquid biopsies in women at high-risk for HGOC and the application of the BRCA-specific diagnostic assay demonstrates high sensitivity, specificity, technical feasibility and safety. Similar classifier for an average-risk population is warranted.

Breast density and risk of breast cancer.

Early studies reported a 4- to 6-fold risk of breast cancer between women with extremely dense and fatty breasts. As most early studies were case-control studies, we took advantage of a population-based screening program to study density and breast cancer incidence in a cohort design. In the Capital Region, Denmark, women aged 50 to 69 are invited to screening biennially. Women screened November 2012 to December 2017 were included, and classified by BI-RADS density code, version 4, at first screen after recruitment. Women were followed up for incident breast cancer, including ductal carcinoma in situ (DCIS), to 2020 in nationwide pathology data. Rate ratios (RRs) and 95% confidence intervals (CI) were compared across density groups using Poisson-regression. We included 189 609 women 1 067 282 person-years and 4110 incident breast cancersDCIS. Thirty-three percent of women had BI-RADS density code 1 38% code 2 24% code 3 4.7% code 4 and missing 0.3%. Using women with BI-RADS density code 1 as baseline women with code 2 had RR 1.69 (95% CI 1.56-1.84) women with code 3, RR 2.06 (95% CI 1.89-2.25) and women with code 4, RR 2.37 (95% CI 1.05-2.74). Results differed between observations accumulated during screening and above screening age. Our results indicated less difference in breast cancer risk across level of breast density than normally stated. Translated into absolute risk of breast cancer after age 50, we found a 6.2% risk for the one-third of women with lowest density, and 14.7% for the 5% of women with highest density.

Childhood body mass index trajectories, adult-onset type 2 diabetes, and obesity-related cancers.

Elevated childhood body mass index (BMI), commonly examined as a once-only value, increases the risk of cancer and type 2 diabetes (T2D) in adulthood. Continuous exposure to adiposity during childhood may further increase cancer risk. We examined whether longitudinal childhood BMI trajectories were associated with adult obesity-related cancer and the role of adult-onset T2D in these associations. Five sex-specific latent class BMI trajectories were generated for 301 927 children (149 325 girls) aged 6-15 years from the Copenhagen School Health Records Register. Information on obesity-related cancers and T2D was obtained from national health registers. Incidence rate ratios (IRR), cumulative incidences, and confidence intervals (CI) were estimated using Poisson regressions. Compared with the average childhood BMI trajectory (containing approximately 40% of individuals), the rate of obesity-related cancer (excluding breast cancer) increased with higher childhood BMI trajectories among women. The highest rates occurred in the overweight (IRR 1.27, 95% CI 1.17 to 1.38) and obesity (IRR 1.79, 95% CI 1.53 to 2.08) BMI trajectories. Similar patterns were observed among men. In contrast, women with the obesity childhood BMI trajectory had the lowest rate of pre- and postmenopausal breast cancer (IRR 0.59, 95% CI 0.43 to 0.80, and IRR 0.41, 95% CI 0.30 to 0.57, respectively). For all trajectories, the cumulative risk of obesity-related cancer increased with adult-onset T2D. Consistent childhood overweight or obesity may increase the rates of adult obesity-related cancer and decrease the rates of breast cancer. Adult-onset T2D conferred additional risk for obesity-related cancer, but the effect did not differ across childhood BMI trajectories.

Breast Cancer Metastatic Dormancy and Relapse An Enigma of Microenvironment(s).

Multiple factors act in concert to define the fate of disseminated tumor cells (DTC) to enter dormancy or develop overt metastases. Here, we review these factors in the context of three stages of the metastatic cascade that impact DTCs. First, cells can be programmed within the primary tumor microenvironment to promote or inhibit dissemination, and the primary tumor can condition a premetastatic niche. Then, cancer cells from the primary tumor spread through hematogenous and lymphatic routes, and the primary tumor sends cues systematically to regulate the fate of DTCs. Finally, DTCs home to their metastatic site, where they are influenced by various organ-specific aspects of the new microenvironment. We discuss these factors in the context of breast cancer, where about one-third of patients develop metastatic relapse. Finally, we discuss how the standard-of-care options for breast cancer might affect the fate of DTCs.

Radiodynamic therapy with acridine orange local administration as a new treatment option for primary and secondary bone tumours.

Acridine orange (AO) demonstrates several biological activities. When exposed to low doses of X-ray radiation, AO increases the production of reactive radicals (radiodynamic therapy (AO-RDT)). We elucidated the efficacy of AO-RDT in breast and prostate cancer cell lines, which are likely to develop bone metastases. We used the mouse osteosarcoma cell line LM8, the human breast cancer cell line MDA-MB-231, and the human prostate cancer cell line PC-3. Cultured cells were exposed to AO and radiation at various concentrations followed by various doses of irradiation. The cell viability was then measured. In vivo, each cell was inoculated subcutaneously into the backs of mice. In the AO-RDT group, AO (1.0 μg) was locally administered subcutaneously around the tumour followed by 5 Gy of irradiation. In the radiation group, 5 Gy of irradiation alone was administered after macroscopic tumour formation. The mice were killed on the 14th day after treatment. The change in tumour volume by AO-RDT was primarily evaluated. The viability of LM8, MDA-MB-231, and PC-3 cells strongly decreased at AO concentration of 1.0 μgml and a radiation dose of 5 Gy. In xenograft mouse model, the AO-RDT also showed a strong cytocidal effect on tumour at the backside in osteosarcoma, breast cancer, and prostate cancer. AO-RDT treatment was more effective for tumour control than radiotherapy in breast cancer. AO-RDT was effective in preventing the proliferation of osteosarcoma, breast cancer, and prostate cancer cell lines in vitro. The reduction in tumour volume by AO-RDT was also confirmed in vivo.Cite this article

Challenges of implementing an integrated electronic health record system in the Breast and Endocrine Clinic at Tygerberg Hospital, Cape Town, South Africa.

To the Editor In low- to middle-income countries, the majority of patients with breast cancer are diagnosed with locally advanced disease. This remains a problem at the Tygerberg Hospital breast clinic in Cape Town, South Africa, with 60% of all patients presenting with stage 3 or 4 disease at the time of diagnosis. The reasons cited are multiple and include fear, unawareness of disease severity, concerns surrounding losing a breast, unreliable transportation, referral difficulties and financial constraints.1.

Computationl and Molecular Docking Studies of New Benzene Sulfonamide Drugs with Anticancer and Antioxidant Effec.

The studies on the potential usage of benzene sulfonamide derivatives as anticancer agents are limited. Thus, in this study, a series of new sulfonamide drugs are synthesized by reacting aldehydes thio-semi-carbazones derivatives with benzene sulphonyl chloride to form benzylidene-N-(phenylsulfonyl) hydrazine-1-carbothioamide derivatives. Spectral techniques, such as Fourier-transform infrared analysis (FT-IR), proton nuclear magnetic resonance (1HNMR) and mass spectroscopy, are used to characterize the newly synthesized compounds. The two derivatives, 2-(4-methoxy benzylidene)-N-(phenylsulfonyl) hydrazine-1-carbothioamide (4c) and 2-(4-dimethylamino) benzylidene)-N-(phenylsulfonyl) hydrazine-1-carbothioamide (4e), show the most potent anticancer effects against MCF-7 breast carcinoma cell lines. Meanwhile, these two derivatives show the lowest antioxidant activities. To study the anti-breast cancer activity of the newly synthesized compounds, a molecular docking study is used to analyze the binding energy for the nonbonding interactions between the ligands (studied compounds) and receptor (4PYP (pdb code 4FA2)) against human breast cancer (MCF-7) cells. The bioavailability of all studied compounds is confirmed by pharmacological investigations using Mol inspiration and absorption, distribution, metabolism, excretion, and toxicity online servers.

Prognostic Factors for Bone Survival and Functional Outcomes in Patients With Breast Cancer Spine Metastases.

According to the Global Cancer Statistics 2020 report, breast cancer is the most commonly diagnosed cancer worldwide. Patients with mammary cancer live longer due to the continuous optimization of chemotherapy, targeted drugs, and hormone therapy, which will inevitably lead to an increase in the prevalence of metastatic bone tumors. Bone metastasis affects approximately 8% of patients with mammary cancer, with the spine being the most common site. Metastatic neoplasms can invade the centrum and its attachments, leading to local pain, spinal instability, vertebral pathological fractures, spinal cord compression, impaired neurological function, and paralysis, ultimately reducing the quality of life. Multidisciplinary and personalized management using analgesic drugs, endocrine therapy, corticosteroid therapy, chemotherapy, bisphosphonates, immunotherapy, targeted drugs, radiotherapy, and surgery has been advocated for the treatment of spinal metastases. Multiple paradigms and systems have been proposed to determine suitable treatments. In the early stages, the occurrence of metastasis indicates a terminal stage of the tumor process in patients with malignant tumors, implying that their lifespan is limited. As a result, the choice of treatment is heavily influenced by longevity. However, with the development of treatment methods, the lifespan of patients with tumors has considerably increased in recent years. This leads to the choice of patients treatment, which depends not only on the patients survival, but also on the radiotherapy or postoperative functional outcomes. Nevertheless, they fall short of determining the variables that affect survival and functional outcomes in histology-specific subgroups of breast cancer. To accurately predict the bone survival and functional outcomes of patients with breast cancer spine metastases a review of prognostic factors was performed.

EphA1 receptor tyrosine kinase is localized to the nucleus in rhabdomyosarcoma from multiple species.

While the typical role of receptor tyrosine kinases is to receive and transmit signals at the cell surface, in some cellular contexts (particularly transformed cells) they may also act as nuclear proteins. Aberrant nuclear localization of receptor tyrosine kinases associated with transformation often enhances the transformed phenotype (i.e. nuclear ErbBs promote tumor progression in breast cancer). Rhabdomyosarcoma (RMS), the most common soft tissue tumor in children, develops to resemble immature skeletal muscle and has been proposed to derive from muscle stemprogenitor cells (satellite cells). It is an aggressive cancer with a 5-year survival rate of 33% if it has metastasized. Eph receptor tyrosine kinases have been implicated in the development and progression of many other tumor types, but there are only two published studies of Ephs localizing to the nucleus of any cell type and to date no nuclear RTKs have been identified in RMS. In a screen for protein expression of Ephs in canine RMS primary tumors as well as mouse and human RMS cell lines, we noted strong expression of EphA1 in the nucleus of interphase cells in tumors from all three species. This localization pattern changes in dividing cells, with EphA1 localizing to the nucleus or the cytoplasm depending on the phase of the cell cycle. These data represent the first case of a nuclear RTK in RMS, and the first time that EphA1 has been detected in the nucleus of any cell type.

Human Papillomavirus 42 Drives Digital Papillary Adenocarcinoma and Elicits a Germ Cell-like Program Conserved in HPV-Positive Cancers.

The skin is exposed to viral pathogens, but whether they contribute to the oncogenesis of skin cancers has not been systematically explored. Here we investigated 19 skin tumor types by analyzing off-target reads from commonly available next-generation sequencing data for viral pathogens. We identified human papillomavirus 42 (HPV42) in 96% (n 4547) of digital papillary adenocarcinoma (DPA), an aggressive cancer occurring on the fingers and toes. We show that HPV42, so far considered a nononcogenic, low-risk HPV, recapitulates the molecular hallmarks of oncogenic, high-risk HPVs. Using machine learning, we find that HPV-driven transformation elicits a germ cell-like transcriptional program conserved throughout all HPV-driven cancers (DPA, cervical carcinoma, and head and neck cancer). We further show that this germ cell-like transcriptional program, even when reduced to the top two genes (CDKN2A and SYCP2), serves as a fingerprint of oncogenic HPVs with implications for early detection, diagnosis, and therapy of all HPV-driven cancers. We identify HPV42 as a uniform driver of DPA and add a new member to the short list of tumorigenic viruses in humans. We discover that all oncogenic HPVs evoke a germ cell-like transcriptional program with important implications for detecting, diagnosing, and treating all HPV-driven cancers. See related commentary by Starrett et al., p. 17. This article is highlighted in the In This Issue feature, p. 1.

Urinary Cell-Free DNA in Liquid Biopsy and Cancer Management.

The current methodology used to detect, diagnose, and monitor many types of cancers requires invasive tissue biopsy testing. Recently, liquid biopsy using blood, plasma, urine, saliva, and various other bodily fluids has shown utility to solve many issues associated with tissue biopsy. Bloodplasma has received most of the attention within the liquid biopsy field, however, obtaining blood samples from patients is still somewhat invasive and requires trained professionals. Using urine to detect cell-free DNA cancer biomarkers offers a truly non-invasive sampling method that can be easily and reproducibly conducted by patients. Novel technologies and approaches have made the detection of small quantities of cell-free tumor DNA of varying lengths possible. Recent studies using urine circulating tumor DNA to detect cancer mutations and other biomarkers have shown sensitivity comparable to bloodplasma cell-free DNA liquid biopsy for many cancer types. Thus, urine cell-free DNA liquid biopsy may replace or provide supplementary information to tissueblood biopsies. Further investigation with larger patient cohorts and standardization of pre-analytical factors is necessary to determine the utility of urine cell-free DNA liquid biopsy for cancer detection, diagnosis, and monitoring in a clinical setting. In this mini-review we discuss the biological aspects of cell-free DNA in urine, numerous studies using urine cell-free DNA to detect urological cancers, and recent studies using urine cell-free DNA to detect and monitor non-urological cancers including lung, breast, colorectal, and other cancers.

Fear-focused Self-compassion Therapy for young breast cancer patients fear of cancer recurrence Study protocol of a randomized controlled trial.

In China, there are a growing number of young women being diagnosed with breast cancer. Fear of Cancer Recurrence (FCR) has become one of the major psychological concerns reported by young breast cancer patients. Yet, there is a lack of psychological intervention tailored for reducing FCR for Chinese young breast cancer patients. In the current study, the Fear-focused Self-compassion Therapy is developed to help Chinese young breast cancer patients to manage FCR. The therapy was developed based on FCR development theories and self-compassion related therapy. The primary objective is to evaluate the short-term and long-term effectiveness of Fear-focused Self-compassion Therapy. The secondary objective is to examine the underlying mechanisms of therapy in reducing FCR in young breast cancer patients. The Fear-focused Self-compassion Therapy consists of 8-week face to face group sessions. This study will be a randomized controlled trial with 160 Chinese young female breast cancer patients with severe FCR. Participants will be randomized to the therapy group or a usual care control group (11). Measurements will be completed at baseline, immediately completing intervention, 3, 6, and 12 months later. Primary outcomes are FCR severity, and secondary outcomes include symptoms of depression and anxiety, satisfaction with therapy, and cost-effectiveness of the therapy. If successful, this study will provide an effective psychological intervention to treat FCR for young breast cancer patients in China, and illuminate the underlying mechanisms of the Fear-focused Self-compassion Therapy in reducing FCR. ClinicalTrials.gov NCT04965428. Registered 23rd July 2021, httpsclinicaltrials.govct2showNCT04965428condfearofcancerrecurrencedraw2rank1.

Higher brain structural heterogeneity in schizophrenia.

As a highly heterogeneous disorder, schizophrenia shows notable interindividual variation in clinical manifestations. On that account, an increasing number of studies begin to examine the interindividual variability in neuroimaging characterization in schizophrenia. However, whether schizophrenia demonstrates higher interindividual morphological variability than health controls (HCs) remains unknown. T1-weighted anatomical images were obtained from patients with schizophrenia (

Role of High-Dose Adjuvant Chemotherapy Followed by Autologous Stem Cell Transplantation in Locally Advanced Triple-Negative Breast Cancer A Retrospective Chart Review.

Women with locally advancedhigh-risk triple-negative breast cancer treated with the current standard chemotherapy continue to have a poor prognosis. High-dose chemotherapy with autologous stem cell transplant as treatment for locally advancedhigh-risk breast cancer remains controversial due to a lack of survival benefit seen in previous phase III trials. However, these trials evaluated a heterogeneous group of patients with different receptor subtypes. A marginal benefit was observed in certain subgroups. We report long-term outcomes of women with stage IIB or III triple-negative breast cancer treated with high-dose chemotherapy followed by autologous stem cell transplant at our institution between 1995 and 2001. This is a retrospective analysis of stage IIB or stage III triple-negative breast cancer treated with high-dose chemotherapy followed by autologous stem cell transplant. We excluded women with hormone-positive, HER2neu-positiveunknown, andor metastatic disease prior to transplant as per updated AJCC 7 Twenty-nine women (2 stage IIB and 27 stage III) were evaluated. The median age at diagnosis was 43 years (IQR 40, 51). Eleven patients had 4-9 regional lymph nodes (LN) involved and 16 had 10 involved LNs. Four patients had T4 or inflammatory breast cancer and two had ipsilateral supraclavicular LNs involved. The median follow-up time is 16 years (95% CI 12, 19, range <1-19 y) posttransplant. The median overall survival was 15 years (95% CI 3, 19) the median DFS was 14 years (95% CI 1, 19). This study of locally advancedhigh-risk triple-negative breast cancer treated with adjuvant high-dose chemotherapy and autologous stem cell transplant reveals high overall survival rate. With the current improvement in treatment-related mortality, re-evaluating this approach in this subset of high-risk breast cancer in prospective randomized studies may be worthwhile.

A Regulatory Network Analysis of the Importance of USP15 in Breast Cancer Metastasis and Prognosis.

Ubiquitin-specific protease15(USP15), is the 16th identified protease in the USP family and is a key protein in tumorigenesis. However, the predictive value and regulatory mechanism of USP15 in breast cancer are unclear. The GEPIA, UALCAN, GeneMANIA, and STRING databases were applied to explore the expression of USP15 in breast cancer and associated proteins. In addition, the TIMER database was evaluated for immune infiltration patterns. Moreover, protein immunoblotting assay, cell scratching assay, small compartment invasion assay, 3D stromal gel assay, immunoprecipitation assay, and immunohistochemistry (IHC) were used to USP15 regulatory mechanisms in breast cancer. In BRCA, several databases, including GEPIA and UALCAN, describe the upregulation of total protein levels and USP15 phosphorylation. In addition, the expression of USP15 was significantly correlated with gender and clinical stage. Overall survival (OS) was lower in patients with high USP15 expression. Functional network analysis showed that USP15 is involved in tumor-associated pathways, DNA replication, and cell cycle signaling through TGF These findings demonstrate that high USP15 expression indicates poor prognosis in BRCA and reveal potential regulatory networks and the positive relationship with immune infiltration. Thus, USP15 may be an attractive predictor for BRCA.

Pattern of Emergency Presentation of Patients with Breast Cancer at the University of Benin Teaching Hospital.

Breast cancer is the most common malignancy affecting women in Nigeria. Presentation is usually elective. However, some patients present as an emergency with complications of the disease and its treatment. This study aimed to capture the features of this population of patients with breast cancer presenting as an emergency. The study was a prospective cross-sectional study conducted between March 2021 and February 2022. All the patients with histologically diagnosed breast cancer presenting as an emergency were recruited into the study. Relevant information was retrieved and analysed. Over the study period, 34 patients were recruited. They were all females and ages ranged between 27 and 74 years of age (mean 45.56 ± 11.71 years), and the highest incidence was in the fifth decade of life. The first symptom in all patients was a breast lump, and the duration of disease ranged between 3 and 84 months (mean 29.21 ± 22.38 months). The right breast was most commonly involved, and invasive ductal carcinoma (no specific type) was the commonest histologic type in 88.24% of cases. Over half of the patients seen had received no treatment after establishing the diagnosis of breast cancer. For those who received treatment, radiotherapy was the least accessed form of treatment. The most common symptoms were difficulty breathing and jaundice (29.41% each), and metastatic disease was the most common diagnosis. The duration of admission ranged between 1 and 35 days, and a mortality rate of 45.45% was recorded. The most common indication for emergency presentation in patients with breast cancer was metastatic disease.

Opposing inflammatory biomarker responses to sleep disruption in cancer patients before and during oncological therapy.

Sleep disruption is known to be highly prevalent in cancer patients, aggravated during oncological treatment and closely associated with reduced quality of life, therapeutic outcome and survival. Inflammatory factors are associated with sleep disruption in healthy individuals and cancer patients, but heterogeneity and robustness of inflammatory factors associated with sleep disruption and how these are affected by oncological therapy remain poorly understood. Furthermore, due to the complex crosstalk between sleep-, and therapy-associated factors, including inflammatory factors, there are currently no established biomarkers for predicting sleep disruption in patients undergoing oncological therapy. We performed a broad screen of circulating biomarkers with immune-modulating or endocrine functions and coupled these to self-reported sleep quality using the Medical Outcomes Study (MOS) sleep scale. Ninety cancer patients with gastrointestinal, urothelial, breast, brain and tonsillar cancers, aged between 32 and 86 years, and scheduled for adjuvant or palliative oncological therapy were included. Of these, 71 patients were evaluable. Data was collected immediately before and again 3 months after onset of oncological therapy. Seventeen among a total of 45 investigated plasma proteins were found to be suppressed in cancer patients exhibiting sleep disruption prior to treatment onset, but this association was lost following the first treatment cycle. Patients whose sleep quality was reduced during the treatment period exhibited significantly increased plasma levels of six pro-inflammatory biomarkers (IL-2, IL-6, IL-12, TNF-a, IFN-g, and GM-CSF) 3 months after the start of treatment, whereas biomarkers with anti-inflammatory, growth factor, immune-modulatory, or chemokine functions were unchanged. Our work suggests that biomarkers of sleep quality are not valid for cancer patients undergoing oncological therapy if analyzed only at a single timepoint. On the other hand, therapy-associated increases in circulating inflammatory biomarkers are closely coupled to reduced sleep quality in cancer patients. These findings indicate a need for testing of inflammatory and other biomarkers as well as sleep quality at multiple times during the patient treatment and care process.

Cuproptosis Combined with lncRNAs Predicts the Prognosis and Immune Microenvironment of Breast Cancer.

Breast cancer (BC), the most common cancer in women, is caused by the uncontrolled proliferation of mammary epithelial cells under the action of a variety of carcinogenic factors. Cuproptosis-related targets have been found to be closely associated with breast cancer development. TCGA obtained 1226 tumor samples, 1073 clinical data, and 37 lncRNAs during univariate Cox multivariate analysis. We used nonnegative matrix factoring (NMF) agglomeration to spot thirty-three potential molecular subsets with totally different cuproptosis-related lncRNA expression patterns. The least absolute shrinkage and selection operator (LASSO) formula and variable Cox multivariate analysis were not used to construct the best prognostic model. The variations in neoplasm mutation burden and factor gene ontology (GO) and gene set enrichment analysis (GSEA) within the high- and low-risk teams were analyzed, and therefore, the potential mechanism of the development of carcinoma was analyzed. We created a prognostic profile consisting of nineteen cuproptosis-related genes (NFE2L2, LIPT1, LIPT2, DLD, etc.) and their connected targets. The correlation between tumor mutational burden (TMB) and clinical manifestations of tumors demonstrates the importance of high- and low-expression bunch data on the incidence of clinical manifestations of tumors. The area under the curve (AUC) shows moderate prophetic power for copper mortality. GO enrichment analysis showed that immunorelated responses were enriched. Correlation analysis of immune cells showed that pathology could play an important role in the prevalence and prognosis of tumors, and there were variations in immune cells between the probable and low-risk groups. Our study suggests that the prognostic characteristic genes associated with cuproptosis can be used as new biomarkers to predict the prognosis of breast cancer patients. In addition, we found that immunotherapy may play a key role in breast cancer treatment regimens. Levels of immune-associated cells and pathways vary significantly among risk groups of breast cancer patients.

Planning and Treatment Recommendations for Breast Proton Therapy From a Single Centers Experience.

Proton therapy use for breast cancer has grown due to advantages in coverage and potentially reduced late toxicities compared with conventional radiation therapy. We aimed to provide recommendations for robustness criteria, daily imaging, and quality assurance computed tomography (QA CT) frequency for these patients. All patients treated for localized breast cancer at the Johns Hopkins Proton Center between November 2019 and February 2022 were eligible for inclusion. Daily shift information was extracted and examined through control charts. If an adaptive plan was used, the time to replan was recorded. Three and 5 mm setup uncertainty was used to calculate robustness. Robust evaluation of QA CTs was compared with initial robustness range for breastchest wall and lymph node target coverage. Sixty-six patients were included 19 with intact breast, 25 with non-reconstructed chest wall, and 22 with chest wall plus expanders or implants. Sixteen percent, 13%, and 41% of breast, chest wall, and expanderimplant patients had a replan. Only patients with expanders or implants required 2 adaptive plans. Daily shift data showed large variation and did not correlate with plan adaptation. Patients without adaptive plans had QA CTs with dose-volume histogram metrics within robustness more frequently than those with adaptive plans. Using 3 mm robustness for patients who did not require an adaptive plan, 91% to 100% of patients had QA CTs within robustness, while 55% to 60% of patients with an adaptive plan had QA CTs within robustness for the axilla, internal mammary nodes, and supraclavicular nodes. Five millimeter setup uncertainty did not significantly improve this. We recommend using daily cone beam CT because of the large variation in daily setup with 3 mm setup uncertainty in robustness analysis. If daily cone beam CT imaging is not available, then larger setup uncertainty should be used. Two QA CTs should be conducted during treatment if the patient has expanders or implants otherwise, one QA CT is sufficient.

Coordinated regulation of BACH1 and mitochondrial metabolism through tumor-targeted self-assembled nanoparticles for effective triple negative breast cancer combination therapy.

The poor prognosis of triple negative breast cancer (TNBC) results from a lack of approved targeted therapies coupled with aggressive proliferation and metastasis, which is associated with high recurrence and short overall survival. Here we developed a strategy by employing tumor-targeted self-assembled nanoparticles to coordinately regulate BACH1 (BTB domain and CNC homology 1) and mitochondrial metabolism. The BACH1 inhibitor hemin and mitochondria function inhibitor berberine derivative (BD) were used to prepare nanoparticles (BH NPs) followed by the modification of chondroitin sulfate (CS) on the surface of BH NPs to achieve tumor targeting (CSBH NPs). CSBH NPs were found to be able to inhibit tumor migration and invasion by significantly decreasing the amounts of tumor cell metabolites, glycolysis and metastasis-associated proteins, which were related to the inhibition of BACH1 function. Meanwhile, decreased mitochondrial membrane potential, activated caspase 39 and increased ROS production demonstrated coordinated regulation of BACH1 and mitochondrial metabolism. In a xenograft mice model of breast cancer, CSBH NPs significantly inhibited tumor growth and metastasis due to the synergetic effect of hemin and BD without showing obvious toxicities for major organs. In sum, the results of efficacy and safety experiments suggest potential clinical significance of the prepared self-assembled CSBH nanoparticles for the treatment of TNBC.

Distorted body schema after mastectomy with immediate breast reconstruction a 4-month follow up study.

After breast cancer, some patients report residual pain-related upper limb disability without physical impairment. Although pain and altered proprioception are known to affect the working body schema (WBS), there is little available evidence investigating the WBS of breast cancer survivors (BrCS). WBS-body representations in the brain-affect the neuromatrix that modulates pain sensitivity and the threshold for threatening stimuli. The aim of this study was to investigate whether WBS was disrupted after mastectomy with immediate breast reconstruction (IBR) for breast cancer and whether pain and proprioceptive changes affected WBS. Thirty-five BrCS participated in the 4-month follow-up study. They were observed at 1 and 4 months postoperatively. The main outcome measures were the left right judgement test (LRJT) results, absolute angle error, pectoralis minor length index (PMI), pain, and Quick-Disabilities of the Arm, Shoulder, and Hand (Q-DASH) score. They were measured at each observation, and parametric tests were performed to identify the nature of WBS. Both the reaction time and accuracy of the hand LRJT were poorer than those of the foot and back LRJT ( To the best of our knowledge, this is the first study providing the nature of WBS after mastectomy with IBR. In this population, it is necessary to postoperatively preserve WBS integrity for pain and upper limb disability.

How to Manage and Monitor Cardiac Dysfunction in Patients With Metastatic HER2-Positive Breast Cancer.

• Targeted therapies improve clinical outcomes in HER2 metastatic breast cancer. • There is thus far minimal signal of increased risk of cardiotoxicity from novel HER2 targeted therapies. • Cancer therapy benefit drives clinical decision-making with LV dysfunction. • The frequency of cardiac monitoring should be based on a risk-benefit approach. Figure see text

Self-Reported Physical Activity, QoL, Cardiac Function, and Cardiorespiratory Fitness in Women With HER2 Breast Cancer.

Women treated for breast cancer are at risk for worsening health-related quality of life (QoL), cardiac function, and cardiorespiratory fitness. The aim of this study was to assess the associations of self-reported moderate to vigorous intensity physical activity (MVPA) during cancer treatment with concurrent measures of QoL and cardiac function and with post-treatment cardiorespiratory fitness in women with human epidermal growth factor receptor 2-positive breast cancer receiving sequential anthracyclines and trastuzumab. EMBRACE-MRI 1 (Evaluation of Myocardial Changes During Breast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI) study participants who completed questionnaires for MVPA (modified Godin Leisure Time Physical Activity Questionnaire) and QoL (EQ-5D-3L, Minnesota Living With Heart Failure Questionnaire) and cardiac imaging every 3 months during treatment and post-treatment cardiopulmonary exercise testing were included. Participants engaging in ≥90 minutes of MVPA each week were labeled active. Generalized estimation equations and linear regression analyses were used to assess concurrent and post-treatment associations with MVPA and activity status, respectively. Eighty-eight participants were included (mean age 51.4 ± 8.9 years). Mean MVPA minutes, QoL, and cardiac function (left ventricular ejection fraction, global longitudinal strain, EA ratio, and Ee ratio) worsened by 6 months into trastuzumab therapy. Higher MVPA (per 30 minutes) during treatment was associated with better concurrent overall (β -0.42) and physical (β -0.24) Minnesota Living With Heart Failure Questionnaire scores, EQ-5D-3L index (β 0.003), visual analogue scale score (β 0.43), diastolic function (EA ratio β 0.01), and global longitudinal strain (β 0.04) at each time point ( Higher self-reported MVPA during treatment for human epidermal growth factor receptor 2-positive breast cancer was associated with better QoL and diastolic and systolic left ventricular function measures during treatment and better post-treatment cardiorespiratory fitness.

The Continued Importance of Promoting Exercise as Part of Oncology Care for Breast Cancer Patients.

Figure see text

Discovery of Promising Inhibitors of Epidermal Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), Estrogen Receptor (ER), and Phosphatidylinositol-3-kinase a (PI3Ka) for Personalized Breast Cancer Treatment.

Despite the rapid developments and advancements to improve treatments, Breast cancer remains one of the deadliest health challenges and the most frequently diagnosed tumor. One of the major problems with treatment is the unique difference that each cancerous cell exhibits. As a result, treatment of breast cancer has now become more personalized based on the specific features of the tumor such as overexpression of growth factor receptors (Epidermal growth factor receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2)), hormone receptors (Human Estrogen receptor alpha (ER)) and kinases involved in pivotal signaling associated with growth (Phosphatidylinositol 3-kinase (PI3K)). Several chemotherapeutic agents have been developed to curb the menace, but the associated adverse drug effects cannot be overlooked. To this end, this study employed a molecular modeling approach to identify novel compounds of natural origin that can potentially antagonize the receptors (mentioned above) associated with the pathophysiology of breast cancer and at the same time pose very little or no side effects. The results of the molecular model of biological interactions between a library of 118 anthocyanins and the binding pockets of the protein targets identified 5 compounds (Pelargonin, Delphinidin 3-

Relationships of Cuproptosis-Related Genes With Clinical Outcomes and the Tumour Immune Microenvironment in Hepatocellular Carcinoma.

Novel iron chelator SK4 demonstrates cytotoxicity in a range of tumour derived cell lines.

Iron is an essential micronutrient due to its involvement in many cellular processes including DNA replication and OXPHOS. Tumors overexpress iron metabolism linked proteins which allow for iron accumulation driving high levels of proliferation. Our group has designed novel iron chelator SK4 which targets cancers iron addiction. SK4 comprises of two key moieties an iron chelation moiety responsible for cytotoxicity and an amino acid moiety which allows entry through amino acid transporter LAT1. We selected LAT1 as a route of entry as it is commonly overexpressed in malignant tumors. SK4 has previously demonstrated promising results in an

Persistent cancer-related fatigue after breast cancer treatment predicts postural sway and post-exertional changes in sit-to-stand strategy.

Chemotherapy-induced peripheral neuropathy (CIPN) is considered a primary mechanism of imbalance among women diagnosed with breast cancer. Recent evidence, however, suggests that cancer-related fatigue (CRF) may also influence balance. Examine the contributions of CRF and CIPN to static and dynamic balance before and after a period of fatiguing exercise. This is a secondary analysis of data examining functional differences between women with breast cancer with and without persistent CRF. Postural sway was measured during static standing and the rising phase of an instrumented sit-to-stand (ISTS) before and after exercise. Regression analyses were performed to determine how CRF and severity of CIPN predicted sway and how much variance was attributable to each. Greater CRF predicted increased pre-, This analysis is limited by its small and demographically homogenous sample. These results suggest that CRF may influence balance independent of CIPN symptoms. While CIPN remains a risk factor for imbalance in this population, CRF warrants consideration in clinical practice and research as a mechanism of postural instability.

Factors predicting upstaging from clinical N0 to pN2aN3a in breast cancer patients.

With sentinel node metastasis in breast cancer (BC) patients, axillary lymph node (ALN) dissection is often omitted from cases with breast-conserving surgery. Omission of lymph node dissection reduces the invasiveness of surgery to the patient, but it also obscures the number of metastases to non-sentinel nodes. The possibility of finding ≥ 4 lymph nodes (pN2apN3a) preoperatively is important given the ramifications for postoperative treatment. To search for clinicopathological factors that predicts upstaging from N0 to pN2apN3a. Patients who were sentinel lymph node (SLN)-positive and underwent ALN dissection between September 2007 and August 2018 were selected by retrospective chart review. All patients had BC diagnosed preoperatively as N0 with axillary evaluation by fluorodeoxyglucose (FDG) positron emission tomographycomputed tomography and ultrasound (US) examination. When suspicious FDG accumulation was found in ALN, the presence of metastasis was reevaluated by second US. We examined predictors of upstaging from N0 to pN2apN3a. Among 135 patients, we identified 1-3 ALNs (pN1) in 113 patients and ³4 ALNs (pN2apN3a) in 22 patients. Multivariate analysis identified the total number of SLN metastasis, the maximal diameter of metastasis in the SLN (SLNDmax), and FDG accumulation of ALN as predictors of upstaging to pN2apN3a. We identified factors involved in upstaging from N0 to pN2apN3a. The SLNDmax and number of SLN metastasis are predictors of ≥ 4 ALNs (pN2apN3a) and predictors of metastasis to non-sentinel nodes, which have been reported in the past. Attention should be given to axillary accumulations of FDG, even when faint.

Literature-based translation from synthetic lethality screening into therapeutics targets CD82 is a novel target for

Synthetic lethality (SL) is an emerging therapeutic paradigm in cancer. We introduced a different approach to prioritize SL gene pairs through literature mining and

Inhaled Gold Nano-star Carriers for Targeted Delivery of Triple Suicide Gene Therapy and Therapeutic MicroRNAs to Lung Metastases Development and Validation in a Small Animal Model.

Pulmonary metastases pose significant treatment challenges for many cancers, including triple-negative breast cancer (TNBC). We developed and tested a novel suicide gene and therapeutic microRNAs (miRs) combination therapy against lung metastases

Nomograms for prediction of breast cancer in breast imaging reporting and data system (BI-RADS) ultrasound category 4 or 5 lesions A single-center retrospective study based on radiomics features.

To develop nomograms for predicting breast malignancy in BI-RADS ultrasound (US) category 4 or 5 lesions based on radiomics features. Between January 2020 and January 2022, we prospectively collected and retrospectively analyzed the medical records of 496 patients pathologically proven breast lesions in our hospital. The data set was divided into model training group and validation testing group with a 7525 split. Radiomics features were obtained using the PyRadiomics package, and the radiomics score was established by least absolute shrinkage and selection operator regression. A nomogram was developed for BI-RADS US category 4 or 5 lesions according to the results of multivariate regression analysis from the training group. The AUCs of radiomics score consisting of 31 US features was 0.886. The AUC of the model constructed with radiomics score, patient age, lesion diameter identified by US and BI-RADS category involved was 0.956 (95% CI, 0.910-0.972) for the training group and 0.937 (95% CI, 0.893-0.965) for the validation cohort. The calibration curves showed good agreement between the predictions and observations. Both nomogram and radiomics score can be used as methods to assist radiologists and clinicians in predicting breast malignancy in BI-RADS US category 4 or 5 lesions.

Is preoperative ultrasound tumor size a prognostic factor in endometrial carcinoma patients

We aimed to assess the prognostic value of preoperative ultrasound tumor size in EC through a single center, observational, retrospective, cohort study. Medical records and electronic clinical databases were searched for all consecutive patients with EC, preoperative ultrasound scans available to 108 patients were included in the study. OS, DSS and PFS did not significantly differ between the groups based on the different tumor diameter cut-offs. No significant differences were found among the groups sub-stratified by age, BMI, FIGO stage, FIGO grade, lymphovascular space invasion status, myometrial invasion, lymph nodal involvement, histotype, and adjuvant treatment. Preoperative ultrasound tumor size does not appear as a prognostic factor in EC women.

Nomogram for the prediction of triple-negative breast cancer histological heterogeneity based on multiparameter MRI features A preliminary study including metaplastic carcinoma and non- metaplastic carcinoma.

Triple-negative breast cancer (TNBC) is a heterogeneous disease, and different histological subtypes of TNBC have different clinicopathological features and prognoses. Therefore, this study aimed to establish a nomogram model to predict the histological heterogeneity of TNBC including Metaplastic Carcinoma (MC) and Non-Metaplastic Carcinoma (NMC). We evaluated 117 patients who had pathologically confirmed TNBC between November 2016 and December 2020 and collected preoperative multiparameter MRI and clinicopathological data. The patients were randomly assigned to a training set and a validation set at a ratio of 31. Based on logistic regression analysis, we established a nomogram model to predict the histopathological subtype of TNBC. Nomogram performance was assessed with the area under the receiver operating characteristic curve (AUC), calibration curve and decision curve. According to the follow-up information, disease-free survival (DFS) survival curve was estimated using the Kaplan-Meier product-limit method. Of the 117 TNBC patients, 29 patients had TNBC-MC (age range, 29-65 years median age, 48.0 years), and 88 had TNBC-NMC (age range, 28-88 years median age, 44.5 years). Multivariate logistic regression analysis demonstrated that lesion type (p 0.001) and internal enhancement pattern (p 0.001) were significantly predictive of TNBC subtypes in the training set. The nomogram incorporating these variables showed excellent discrimination power with an AUC of 0.849 (95% CI 0.750-0.949) in the training set and 0.819 (95% CI 0.693-0.946) in the validation set. Up to the cutoff date for this analysis, a total of 66 patients were enrolled in the prognostic analysis. Six of 14 TNBC-MC patients experienced recurrence, while 7 of 52 TNBC-NMC patients experienced recurrence. The DFS of the two subtypes was significantly different (p0.035). In conclusion, we developed a nomogram consisting of lesion type and internal enhancement pattern, which showed good discrimination ability in predicting TNBC-MC and TNBC-NMC.

The oncogenic roles of JC polyomavirus in cancer.

JC polyomavirus (JCPyV) belongs to the human polyomavirus family. Based on alternative splicing, the early region encodes the large and small T antigens, while the late region encodes the capsid structural proteins (VP1, VP2, and VP3) and the agnoprotein. The regulatory transcription factors for JCPyV include Sp1, TCF-4, DDX1, YB-1, LCP-1, Purα, GF-1, and NF-1. JCPyV enters tonsillar tissue through the intake of raw sewage, inhalation of air droplets, or parent-to-child transmission. It persists quiescently in lymphoid and renal tissues during latency. Both TGF-β1 and TNF-α stimulates JCPyV multiplication, while interferon-γ suppresses the process. The distinct distribution of caspid receptors (α-2, 6-linked sialic acid, non-sialylated glycosaminoglycans, and serotonin) determines the infection capabilities of JCPyV virions, and JCPyV entry is mediated by clathrin-mediated endocytosis. In permissive cells, JCPyV undergoes lytic proliferation and causes progressive multifocal leukoencephalopathy, while its DNA is inserted into genomic DNA and leads to carcinogenesis in non-permissive cells. T antigen targets p53, β-catenin, IRS, Rb, TGF-β1, PI3KAkt and AMPK signal pathways in cancer cells. Intracranial injection of T antigen into animals results in neural tumors, and transgenic mice develop neural tumors, lens tumor, breast cancer, gastric, Vaters, colorectal and pancreatic cancers, insulinoma, and hepatocellular carcinoma. Additionally, JCPyV DNA and its encoded products can be detected in the brain tissues of PML patients and brain, oral, esophageal, gastric, colorectal, breast, cervical, pancreatic, and hepatocellular cancer tissues. Therefore, JCPyV might represent an etiological risk factor for carcinogenesis and should be evaluated for early prevention, diagnosis, and treatment of cancers.

Thyroid and renal cancers A bidirectional association.

There is a deep interrelation between the thyroid gland and the kidney parenchyma, with dysfunction of the first leading to significant changes in renal metabolism and

Aquaporins New players in breast cancer progression and treatment response.

Aquaporins (AQPs) are a family of small transmembrane proteins that selectively transport water and other small molecules and ions following an osmotic gradient across cell plasma membranes. This enables them to regulate numerous functions including water homeostasis, fat metabolism, proliferation, migration, and adhesion. Previous structural and functional studies highlight a strong biological relationship between AQP protein expression, localization, and key biological functions in normal and cancer tissues, where aberrant AQP expression correlates with tumorigenesis and metastasis. In this review, we discuss the roles of AQP1, AQP3, AQP4, AQP5, and AQP7 in breast cancer progression and metastasis, including the role of AQPs in the tumor microenvironment, to highlight potential contributions of stromal-derived to epithelial-derived AQPs to breast cancer. Emerging evidence identifies AQPs as predictors of response to cancer therapy and as targets for increasing their sensitivity to treatment. However, these studies have not evaluated the requirements for protein structure on AQP function within the context of breast cancer. We also examine how AQPs contribute to a patients response to cancer treatment, existing AQP inhibitors and how AQPs could serve as novel predictive biomarkers of therapy response in breast cancer. Future studies also should evaluate AQP redundancy and compensation as mechanisms used to overcome aberrant AQP function. This review highlights the need for additional research into how AQPs contribute molecularly to therapeutic resistance and by altering the tumor microenvironment.