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A proof-of-concept study of iCope A nurse-led psychoeducational telephone intervention for women attending a rapid diagnostic centre for breast abnormality.

The period between the initial discovery of a suspicious breast lesion and a confirmed diagnosis is a time of significant psychological distress, heightened anxiety, and uncertainty for many women. This proof of concept (PoC) study explored the clinical outcomes and acceptability of iCope, a nurse-led psycho-educational telephone intervention aimed to assist with uncertainty, anxiety and coping in women going through a Rapid Diagnostic Centre (RDC) offering quick diagnosis of breast cancer (same day to three-day post-investigation). Guided by the Uncertainty Theory, and using a one-arm pretest-posttest design, two brief 15-minute telephone sessions were delivered by a nurse prior to the womens day of testing at the RDC and three days after the receipt of their results. Six women completed measures of anxiety, uncertainty, and coping before the clinic visit, three days and three weeks after receiving their test results. Results show that the implementation of the telephone intervention was challenging, yet may offer potential for positive impact. That is, trends of decreased uncertainty and anxiety in participants over time were noted. Considering the difficulty observed in the recruitment and delivering the two interventions in the timeline planned, feasibility testing is recommended before the conduct of a large-scale study.

Prognostic Significance of Preoperative Lactate Dehydrogenase to Albumin Ratio in Breast Cancer A Retrospective Study.

We explored the relationship between platelet count to lymphocyte count ratio (PLR), monocyte count to lymphocyte count ratio (MLR), lactate dehydrogenase to albumin ratio (LAR), and long-term survival in patients with breast cancer. We retrospectively analyzed the clinical and follow-up data of 134 patients with breast cancer. The receiver operating characteristic curve (ROC curve) was used to distinguish between the low and high ratio groups. The chi-square test or Fishers exact test was used to calculate the differences among the investigation factors. The Kaplan-Meier method was used to draw the survival curves. Log rank test was used for univariate analysis, and Cox proportional hazards regression model was used for multivariate analysis. A P value of <0.05 was considered statistically significant. The median follow-up time was 45 months. The PFS rates in the low group (LAR≤3.4066) at 18 months, 24 months, and 36 months were 100%, 100%, and 97.6%, and those in the high group (LAR > 3.4066) were 97.7%, 94.3%, and 87.3%, respectively. LAR was associated with Age (P0.002) and BMI (body mass index) (P0.002). Univariate analysis showed that Tumor size (P0.027), Node positivity (P<0.001), TNM (tumor-node-metastasis) stage (P<0.001), PLR (P0.034), MLR (P0.038), and LAR (P0.035) were significantly associated with PFS (progression-free survival) in breast cancer patients. Multivariate analysis showed that Node positivity (P<0.001) and LAR (P0.035) were associated with PFS, while PLR and MLR were not independent prognostic indicators. Preoperative high LAR will be an independent predictor of prognosis in patients with breast cancer.

Proteome Analysis of Adult Acute Lymphoblastic Leukemia by Two-dimensional Blue NativeSodium Dodecyl Sulfate Gel Electrophoresis.

Despite the significant progress in the treatment of Acute Lymphoblastic Leukemia (ALL) in children, it still remains as one of the most challenging malignancies in adults. Identification of new biomarkers may improve the management of adult ALL. Proteins expressed on the cell surface can be considered as disease-associated biomarkers with potential for diagnosis and targeted therapies. Thus, membrane proteome studies give essential information about the disease-related biomarkers. We applied 2-dimensional blue-native SDS-PAGE technique followed by MALDI-TOFTOF-mass spectrometry to study the cell membrane proteome of peripheral blood mononuclear cells of adult B-ALL patients in comparison to that of the healthy controls. Sixty seven differentially expressed protein spots were detected, among them 52 proteins were found to be up-regulated but the other 15 proteins were down-regulated in B-ALL. Five differentially expressed proteins, involved in energy metabolism pathways, were detected in B-ALL patients compared to the healthy control group. Differentially expressed proteins provide an insight into the molecular biology of B-ALL. Further studies must be done to confirm our data to be considered as potential targets for detection and treatment of B-ALL.

Cancer, diabetes, survival and glycemic control a large multisite analysis.

To determine overall survival (OS) and glycemic control in patients with cancer and diabetes. Patients of our institution with breast, colon, lung, pancreas and prostate cancer were retrospectively reviewed. OS was compared between matched patients with and without diabetes, and changes in glucose value over time were assessed. For 3934 patients each with and without diabetes, adjusted analysis showed no difference in OS according to diabetes status (hazard ratio 1.07 95% CI 0.96-1.20). Mean glucose values decreased over time in patients with and without diabetes (p 0.01). In this large study of patients with five common cancers, the co-occurrence of diabetes did not affect OS. Cancer did not adversely affect glucose levels. The aim of this study was to evaluate survival and glucose control in patients with cancer and diabetes at three separate geographic locations in a single health system. From an institutional cancer registry, we identified patients with breast, colon, lung, pancreas and prostate cancers. Patients with and without diabetes were matched by age, sex, cancer type, staging, geographic location and year of cancer diagnosis. In this study, the co-occurrence of diabetes did not affect overall survival. Cancer did not adversely affect glucose levels.

Impact of KRAS Mutation on Survival Outcome of Patients With Metastatic Colorectal Cancer in Jordan.

Background Colorectal cancer (CRC) is the most prevalent cancer in males, with an incidence rate (IR) of 13.1%, and the second most prevalent cancer in females, with an IR of 8.4%, coming after breast cancer in Jordan. The present study was motivated by conflicting clinical data regarding the prognostic impact of Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation in patients with metastatic colorectal cancer (mCRC). Our study aimed to investigate if KRAS mutation conferred a negative prognostic value in Jordanian patients with mCRC. Materials and methods The current study is a retrospective study that collected data from a cohort of 135 mCRC patients diagnosed between 1 January 2017 and 1 January 2022 at our Oncology Department at the Jordanian Military Cancer Center (MCAC) using our patients electronic medical records. The last follow-up date was 1 September 2022. From the cohort, we obtained data regarding age, sex, date of diagnosis, metastatic spread, KRAS status, either mutated KRAS or wild-type KRAS, and location of the primary tumor. All patients underwent tumor tissue biopsies to determine KRAS mutational status based on quantitative polymerase chain reaction and reverse hybridization from an accredited diagnostic laboratory at Jordan University Hospital. Statistical analysis was carried out to address the associations between

Programmed Cell Death Protein 1 (PD-1) in relation to PANoptosis Immune Pharmacological Targets for Management of Breast Adenocarcinoma.

Programmed cell death protein 1 or Programmed death-1 (PD-1) and Programmed Cell Death Ligand 1 (PD-L1) research have tremendously been taken into great consideration in the field of cancer immune pharmacology. Cancer immunotherapy has been convoyed by a capable outcome over the past few years. PD-1 and PD-L1 play a pivotal role in attenuating immune involvement, modulating the activity of T-cells, and promoting different types of programmed cell death. Participation of antigen-specific T cells and regulatory T cells and their acute mutations during cancer cell invasion and migration may lead to challenges for three programmed cell death methods, namely, pyroptosis, apoptosis, and necroptosis called PANoptosis. This review aimed to explore the correlation between the PD-1PD-L1 pathway in PANoptosis using available recently published literature with several schematic representations. Hopefully, the review will facilitate the biomedical scientist targeting cancer immune pharmacological aspect for the management of Breast Adenocarcinoma shortly.

Longitudinal Association between L1 Trabecular Attenuation from Chest Computed Tomography (CT) and Bone Mineral Density from Dualenergy X-ray Absorptiometry (DXA).

Many studies have shown that vertebral trabecular attenuation measured on CT scan corresponds well to DXA results for bone mineral density. These studies were based on crosssectional data. Hence, there were limitations in explaining the constantly changing vertebral trabecular attenuation from CT and T-score from DXA over time. This study aimed to determine the longitudinal association between the vertebral trabecular attenuation measured on computed tomography (CT) and the T-score measured by dual-energy X-ray absorptiometry (DXA). We performed a database search for 333 patients who underwent surgery for breast cancer, preoperative treatment, and at least one follow-up chest CT and DXA from January, 2013 through May, 2021. One musculoskeletal radiologist measured the mean vertebral trabecular attenuation of lumbar vertebra 1(L1) on axial unenhanced images at the pedicle level by manually placing the region of interest (ROI). DXA of the lumbar spine was performed, and the lowest T-score of the lumbar spine was used for the analysis. We evaluated the association between L1 trabecular attenuation from chest CT and T-score from DXA over time using the generalized estimating equations (GEE) model to analyze longitudinal corrected data. A total of 150 women (mean age, 52.4 ± 11.0 years) were included. There was a statistically significant association between L1 trabecular attenuation from chest CT and T-score from DXA in the unadjusted model (p < 0.001) and adjusted model (p < 0.001). T-score value increased by 0.172 (95% confidence interval (CI) 0.145-0.200, p < 0.001) per 10 unit (HU) of L1 trabecular attenuation at time 0 in unadjusted model and by 0.173 (95% CI 0.143-0.203, p < 0.001) in all adjusted model. We demonstrated that L1 attenuation from chest CT images was longitudinally associated with T-score from DXA, and the degree of association appeared to be decreased over time in breast cancer patients regardless of their medical condition.

Review on Computer Aided Breast Cancer Detection and Diagnosis Using Machine Learning Methods on Mammogram Image.

Machine Learning (ML) plays an essential part in the research area of medical image processing. The advantages of ML techniques lead to more intelligent, accurate, and automatic computeraided detection (CAD) systems with improved learning capability. In recent years, deep learning-based ML approaches developed to improve the diagnostic capabilities of CAD systems. This study reviews image enhancement, ML and DL methods for breast cancer detection and diagnosis using mammogram images and provides an overview of these methods. The analysis of different ways of ML and DL shows that the usages of traditional ML approaches are limited. However, DL techniques have an excellent future for implementing medical image analysis and improving the ability to exist CAD systems. Despite the significant advancements in deep learning methods for analyzing medical images to detect breast cancer, challenges still exist regarding data quality, computational cost, and prediction accuracy.

Ultra-low-coverage genome-wide association study-insights into gestational age using 17,844 embryo samples with preimplantation genetic testing.

Very low-coverage (0.1 to 1×) whole genome sequencing (WGS) has become a promising and affordable approach to discover genomic variants of human populations for genome-wide association study (GWAS). To support genetic screening using preimplantation genetic testing (PGT) in a large population, the sequencing coverage goes below 0.1× to an ultra-low level. However, the feasibility and effectiveness of ultra-low-coverage WGS (ulcWGS) for GWAS remains undetermined. We built a pipeline to carry out analysis of ulcWGS data for GWAS. To examine its effectiveness, we benchmarked the accuracy of genotype imputation at the combination of different coverages below 0.1× and sample sizes from 2000 to 16,000, using 17,844 embryo PGT samples with approximately 0.04× average coverage and the standard Chinese sample HG005 with known genotypes. We then applied the imputed genotypes of 1744 transferred embryos who have gestational ages and complete follow-up records to GWAS. The accuracy of genotype imputation under ultra-low coverage can be improved by increasing the sample size and applying a set of filters. From 1744 born embryos, we identified 11 genomic risk loci associated with gestational ages and 166 genes mapped to these loci according to positional, expression quantitative trait locus, and chromatin interaction strategies. Among these mapped genes, CRHBP, ICAM1, and OXTR were more frequently reported as preterm birth related. By joint analysis of gene expression data from previous studies, we constructed interrelationships of mainly CRHBP, ICAM1, PLAGL1, DNMT1, CNTLN, DKK1, and EGR2 with preterm birth, infant disease, and breast cancer. This study not only demonstrates that ulcWGS could achieve relatively high accuracy of adequate genotype imputation and is capable of GWAS, but also provides insights into the associations between gestational age and genetic variations of the fetal embryos from Chinese population.

Diagnostic accuracy of a three-protein signature in women with suspicious breast lesions a multicenter prospective trial.

Mammography screening has been proven to detect breast cancer at an early stage and reduce mortality however, it has low accuracy in young women or women with dense breasts. Blood-based diagnostic tools may overcome the limitations of mammography. This study assessed the diagnostic performance of a three-protein signature in patients with suspicious breast lesions. This trial (MAST KCT0004847) was a prospective multicenter observational trial. Three-protein signature values were obtained using serum and plasma from women with suspicious lesions for breast malignancy before tumor biopsy. Additionally, blood samples from women who underwent clear or benign mammography were collected for the assays. Among 642 participants, the sensitivity, specificity, and overall accuracy values of the three-protein signature were 74.4%, 66.9%, and 70.6%, respectively, and the concordance index was 0.698 (95% CI 0.656, 0.739). The diagnostic performance was not affected by the demographic features, clinicopathologic characteristics, and co-morbidities of the participants. The present trial showed an accuracy of 70.6% for the three-protein signature. Considering the value of blood-based biomarkers for the early detection of breast malignancies, further evaluation of this proteomic assay is warranted in larger, population-level trials. This Multi-protein Assessment using Serum to deTermine breast lesion malignancy (MAST) was registered at the Clinical Research Information Service of Korea with the identification number of KCT0004847 ( httpscris.nih.go.kr ).

Recent Advancements in Gremlin-1 Breast cancer.

One of the bones morphogenic protein (BMP) antagonists, Gremlin-1 or GREM-1, can bind directly to BMPs. GREM-1 can act in either BMP-dependent or -independent pathways, according to research. It reinforces organogenesis, tissue differentiation, and organ fibrosis. Recent research from numerous studies has demonstrated the significance of GREM-1 in the initiation, progression, and even metastasis of different cancers, including breast, cervical, gastric, and colorectal cancers. This review highlights the function of GREM-1 in the development of breast cancer and its effect on the cellular procedures and signalling pathways involved in carcinogenesis.

Comprehensive targeted treatment options available for Breast cancer stem cells A literature review of the last 10 years developments.

Breast Cancer Stem Cells (BCSCs), unlike normal breast cells, exhibit the potential for self-regeneration and tumour formation and express unique markers. Studies have highlighted their role in tumour progression, recurrence, and treatment resistance. BCSCs can be one of the reasons that resistance is encountered despite recent advances in the treatment of breast cancer (BC). This review underlines the clinical implications at the molecular level of different cellular pathways, cellular level interactions in Tumour Micro Environment (TME), and types of markers and receptors involved in tumorigenesis. It accentuates the importance of comprehensive targeted treatment options available for BCSCs so that targeted modalities can be introduced to deal with treatment resistance. Stem cells (SCs) are a developing field, and limited data is available from our country to use stem cell-targeted treatment plans as a therapeutic option. Therefore, this literature review will provide insight for future research in this domain.

Establishment and characterization of the first patient-derived radiation-induced angiosarcoma xenograft model (RT-AS5).

Angiosarcomas are a heterogeneous group of rare endothelial malignancies with a complex, not completely unravelled biology. They encompass primary (sporadically occurring) angiosarcomas of several origins and secondary angiosarcomas, which often arise due to DNA damaging factors including radiotherapy or ultraviolet light exposure. The optimal treatment of metastatic angiosarcomas is unclear and the prognosis is poor. In order to discover novel treatment strategies for angiosarcomas it is important to take the heterogeneity of these tumors into account. For this reason it is also important to have preclinical models available for the different clinical subtypes. Owing to the rarity of angiosarcomas, models are scarce. So far, only five human cell lines of angiosarcomas (all of the scalp after UV exposure) are available worldwide. In this paper we describe a novel established patient-derived xenograft model of a radiotherapy-induced angiosarcoma of the breast. The tumor was characterized by a MYC amplification, CD31 and ERG immunohistochemical positivity and was further characterized by using next generation sequencing (TruSight Oncology 500) in combination with the R-package XenofilteR to separate mouse from human sequence reads.

Investigation of Shared Genetic Risk Factors Between Parkinsons Disease and Cancers.

Epidemiological studies that examined the association between Parkinsons disease (PD) and cancers led to inconsistent results, but they face a number of methodological difficulties. We used results from genome-wide association studies (GWASs) to study the genetic correlation between PD and different cancers to identify common genetic risk factors. We used individual data for participants of European ancestry from the Courage-PD (Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinsons Disease PD, N 16,519) and EPITHYR (differentiated thyroid cancer, N 3527) consortia and summary statistics of GWASs from iPDGC (International Parkinson Disease Genomics Consortium PD, N 482,730), Melanoma Meta-Analysis Consortium (MMAC), Breast Cancer Association Consortium (breast cancer), the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (prostate cancer), International Lung Cancer Consortium (lung cancer), and Ovarian Cancer Association Consortium (ovarian cancer) (N comprised between 36,017 and 228,951 for cancer GWASs). We estimated the genetic correlation between PD and cancers using linkage disequilibrium score regression. We studied the association between PD and polymorphisms associated with cancers, and vice versa, using cross-phenotypes polygenic risk score (PRS) analyses. We confirmed a previously reported positive genetic correlation of PD with melanoma (G We show evidence in favor of a contribution of pleiotropic genes to the association between PD and specific cancers. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

How Well Does Non-mass Enhancement Correlate With DCISInvasive Cancer

Contiguous non-mass enhancement (NME) often coexists with a solid tumor component on MRI, but it can be challenging to predict whether NME represents invasive breast cancer, ductal carcinoma in situ (DCIS), benign disease, or biopsy site reaction. The purpose of this study was to determine the association between the sizeextent of NME and the presence of invasive cancer andor DCIS on final pathology. This was a single institution retrospective analysis of a prospectively maintained breast cancer registry (2010-2020). Female patients who underwent surgical resection were included if they had a diagnosis of invasive breast cancer (with or without DCIS) and had an MRI showing both a solid mass and contiguous NME. The size of NME on MRI was compared with the size of invasive cancer andor DCIS on the final pathology. From a total of 3443 patients, 225 patients were included. 86.2% had invasive ductal carcinoma (IDC), and 12.0% had invasive lobular carcinoma 76.9% were ER, 16.4% were HER2, and 13.3% were triple negative breast cancer (TNBC). 18.7% received neoadjuvant chemotherapy (NCT) of whom 31% achieved a complete radiographicpathologic response. Pearson correlation coefficients (r) between the size of NME and invasive cancerDCIS showed a strong and positive correlation of MRI NME with DCIS on pathology in patients without NCT. Subgroup analysis showed the strongest correlations for NME and DCIS among non-white (r .70) and HER2 patients (r .74) who did not receive NCT. Strong correlations between NME and DCIS were found for HER2 disease and non-white patients, but only modest correlations were found for other patientdisease characteristics. These correlations may impact decisions in surgical approach.

The Role of Artificial Intelligence in Accurate Interpretation of HER2 Immunohistochemical Scores 0 and 1 in Breast Cancer.

The new human epidermal growth factor receptor (HER)2-targeting antibody-drug conjugate offers the opportunity to treat patients with HER2-low breast cancer. Distinguishing HER2 immunohistochemical (IHC) scores of 0 and 1 is not only critical but also challenging owing to HER2 heterogeneity and variability of observers. In this study, we aimed to increase the interpretation accuracy and consistency of HER2 IHC 0 and 1 evaluation through assistance from an artificial intelligence (AI) algorithm. In addition, we examined the value of our AI algorithm in evaluating HER2 IHC scores in tumors with heterogeneity. AI-assisted interpretation consisted of AI algorithms and an augmenting reality module with a microscope. Fifteen pathologists (5 junior, 5 midlevel, and 5 senior) participated in this multi-institutional 2-round ring study that included 246 infiltrating duct carcinoma cases that were not otherwise specified. In round 1, pathologists analyzed 246 HER2 IHC slides by microscope without AI assistance. After a 2-week washout period, the pathologists read the same slides with AI algorithm assistance and rendered the definitive results by adjusting to the AI algorithm. The accuracy of interpretation accuracy with AI assistance (0.93 vs 0.80), thereby the evaluation precision of HER2 0 and the recall of HER2 1. In addition, the AI algorithm improved the total consistency (intraclass correlation coefficient 0.542-0.812), especially in HER2 1 cases. In cases with heterogeneity, accuracy improved significantly (0.68 to 0.89) and to a similar level as in cases without heterogeneity (accuracy, 0.97). Both accuracy and consistency improved more for junior pathologists than those for the midlevel and senior pathologists. To the best of our knowledge, this is the first study to show that the accuracy and consistency of HER2 IHC 0 and 1 evaluation and the accuracy of HER2 IHC evaluation in breast cancers with heterogeneity can be significantly improved using AI-assisted interpretation.

Homologous Recombination Repair Deficiency An Overview for Pathologists.

The repair of DNA double-stranded breaks relies on the homologous recombination repair pathway and is critical to cell function. However, this pathway can be lost in some cancers such as breast, ovarian, endometrial, pancreatic, and prostate cancers. Cancer cells with homologous recombination deficiency (HRD) are sensitive to targeted inhibition of poly-ADP ribose polymerase (PARP), a key component of alternative backup DNA repair pathways. Identifying patients with cancer with HRD biomarkers allows the identification of patients likely to benefit from PARP inhibitor therapies. In this study, we describe the causes of HRD, the underlying molecular changes resulting from HRD that form the basis of different molecular HRD assays, and discuss the issues around their clinical use. This overview is directed toward practicing pathologists wishing to be informed of this new predictive biomarker, as PARP inhibitors are increasingly used in standard care settings.

HER2-Low Breast Cancer Incidence, Clinicopathologic Features, and Survival Outcomes From Real-World Data of a Large Nationwide Cohort.

Patients with breast cancer (BC) with low levels of human epidermal growth factor receptor 2 (HER2) expression (HER2-low) could benefit from novel antibody-drug conjugates. However, there is conflicting information regarding the characteristics of HER2-low BC and its outcome. We assessed the clinicopathologic characteristics and outcomes of HER2-low BC using real-world data from the Dutch National Pathology Registry. This retrospective study incorporated all patients with primary invasive BC, without neoadjuvant therapy, reported in the Dutch National Pathology Registry synoptic reporting module between 2014 and 2022. HER2 status was categorized as HER2-0 (defined as an immunohistochemistry score of 0 according to the current American Society of Clinical OncologyCollege of American Pathologists guidelines) or HER2-low (immunohistochemistry score 1 or 2 without amplification). Clinicopathologic characteristics and overall survival of HER2-low BC were compared with HER2-0, adjusted for estrogen receptor (ER) status. We included 65,035 patients with BC, resulting in 69,424 tumors. The proportion of HER2-low BC was 62% in the ER cohort and 38% in the ER- cohort. A substantial number of patients had a different HER2 category between the needle biopsy and the corresponding surgical resection (28%) or among multiple tumors (28%). After multivariable logistic analysis, HER2-low tumors were significantly associated with histologic subtype, a higher ER, and lower progesterone receptor expression in the ER cohort, whereas within the ER-cohort, HER2-low tumors were associated with a lower tumor grade. However, the absolute differences were limited, and there was no significant difference in overall survival between HER2-low and HER2-0 tumors within the ER or ER- cohort. The classification of HER2 expression (HER2-0 vs HER2-low) varies between biopsies and corresponding resection specimens and within multiple tumors in the same patient, which could affect clinical decision making in case only HER2-low cases are eligible for novel HER2-targeting agents. The limited follow-up time and the lack of substantial clinicopathologic differences between HER2-low and HER2-0-cases could explain the lack of differences in overall survival.

Diagnostic Accuracy of GATA6 Immunostaining in Sebaceous Tumors of the Skin.

The accurate diagnosis of skin adnexal neoplasms is sometimes challenging but is necessary because medical management and follow-up may differ between tumors. GATA6 transcription factor has been identified as a new marker of the upper folliculosebaceous compartment (lower infundibulum, junctional zone and isthmus, and upper sebaceous gland) in the human skin. We aimed to determine the diagnostic accuracy of GATA6 immunostaining to diagnose sebaceous tumors compared with that to diagnose other adnexal and nonadnexal cutaneous neoplasms. We conducted a retrospective, evaluator-nonblinded study comparing the reference standard (diagnosis by an expert dermatopathologist) with GATA6 immunostaining to identify sebaceous tumors in a cohort containing 234 different tumors. The GATA6 expression score was significatively higher in sebaceous than that in nonsebaceous tumors. In addition, tumors originating from the upper hair follicle showed positive results for GATA6 staining however, they showed lower GATA6 expression scores. Detection of sebaceous tumors using GATA6 positivity had a sensitivity of 95.7% (95% confidence interval 95% CI, 85.8-99.2), specificity of 80.8% (95% CI, 74.5-85.8), positive predictive value of 55.6% (95% CI, 44.7-65.9), and negative predictive value of 98.7% (95% CI, 95.4-99.8). GATA6 showed similar sensitivity to adipophilin, the reference marker however, the specificity of GATA6 was higher, as observed in a cohort of 106 tumors enriched in squamous cell carcinomas with clear-cell histology. In addition, GATA6 positivity was assessed in 39 sebaceous carcinomas and compared with epithelial membrane antigen (EMA), CK7, and androgen receptor (AR) staining results. Although CK7 staining displayed lower diagnostic performances, GATA6 staining showed comparable results as EMA and AR. Finally, we found GATA6 expression in skin metastases of gastrointestinal origin, whereas GATA6 was absent in metastases originating from breast or lung cancers. Overall, our work identified GATA6 immunostaining as a new diagnostic tool for sebaceous tumors.

p53 Expression in Luminal Breast Cancer Correlates With TP53 Mutation and Primary Endocrine Resistance.

TP53 mutation is associated with primary endocrine resistance in luminal breast cancer (BC). Nuclear accumulation of p53, as determined by immunohistochemistry (IHC), is a surrogate marker for TP53 mutation. The immunohistochemical p53 index that defines a p53-positive status is not well established. This study determined the optimal p53 index cutoff to identify luminal BCs harboring TP53 mutations. In total, 364 luminal BCs from the West German Study Group ADAPT trial (NCT01779206) were analyzed for TP53 mutations by next-generation sequencing and for p53 expression by IHC (DO-7 antibody). P53 indices were determined by automated image analysis. All tumors were from patients treated with short-term preoperative endocrine therapy (pET tamoxifen or aromatase inhibitor) before tumor resection. IHC evaluation included needle biopsies before therapy (baseline) and resections specimens after therapy (post-pET). Optimal p53 index cutoffs were defined with Youden statistics. TP53 mutations were detected in 16.3% of BC cases. The median p53 indices were significantly higher in TP53-mutated BCs compared to BCs harboring wild-type TP53 (baseline 47.0% vs 6.4%, P < .001 post-pET 50.1% vs 1.1%, P < .001). Short-term pET decreased p53 indices in BCs harboring wild-type TP53 (P < .001) but not in TP53-mutated BCs (P .102). For baseline biopsies, the optimal p53 index cutoff was ≥34.6% (specificity 0.92, sensitivity 0.63, Youden index 0.54, accuracy 0.87). For post-pET specimens, the optimal cutoff was ≥25.3% (specificity 0.95, sensitivity 0.65, Youden index 0.60, accuracy 0.90). Using these cutoffs to define the p53 status, p53-positive BCs were >2-fold more common in pET nonresponders compared to pET responders (baseline 37162, 22.8% vs 18162, 11.1%, P .007 post-pET 36179, 20.1% vs 16179, 8.9%, P .004). In summary, IHC for p53 identifies TP53-mutated luminal BCs with high specificity and accuracy. Optimal cutoffs are ≥35% and ≥25% for treatment-naïve and endocrine-pretreated patients, respectively.

Early Triple-Negative Breast Cancers in a Singapore Cohort Exhibit High PIK3CA Mutation Rates Associated With Low PD-L1 Expression.

Mutations in the PI3K pathway, particularly PIK3CA, were reported to be intimately associated with triple-negative breast cancer (TNBC) progression and the development of treatment resistance. We profiled PIK3CA and other genes on 166 early-stage TNBC tumors from Singapore for comparison to publicly available TNBC cohorts. These tumors were profiled transcriptionally using a NanoString panel of immune genes and multiplex immunohistochemistry, then manually scored for PD-L1-positivity using 2 clinically relevant clones, SP142 and 22C3. We discovered a higher rate of PIK3CA mutations in our TNBC cohort than in non-Asian cohorts, along with TP53, BRCA1, PTPN11, and MAP3K1 alterations. PIK3CA mutations did not affect overall or recurrence-free survival, and when compared with PIK3CA

Identifying SOX17 as a Sensitive and Specific Marker for Ovarian and Endometrial Carcinomas.

Similar to PAX8, SOX17 was recently identified as a master transcription factor of ovarian cancer based on RNA sequencing data. We explored SOX17 utility in diagnosing ovarian tumors and other gynecologic tumors. We systematically evaluated SOX17 expression on tissue microarrays of 398 ovarian tumors of various types, 93 endometrial carcinomas, 80 cervical carcinomas, and 1371 nongynecologic carcinomas, such as those of kidney, thyroid, breast, colon, bladder, liver, bile duct, adrenal gland, pancreas, brain, and lung and malignant melanoma. In addition, we evaluated SOX17 expression in whole tissue sections from 60 gynecologic carcinomas and 10 angiosarcomas. The results demonstrated that SOX17 was highly expressed in most ovarian and endometrial tumors with strong intensity. However, unlike PAX8, it was predominately negative in other tested tumor types, including kidney and thyroid tumors. In particular, SOX17 was highly expressed in the following pathologic subtypes of ovarian tumors serous carcinoma, clear cell carcinoma, endometrioid carcinoma, and germ cell tumors. SOX17 was mostly negative in mucinous carcinoma and sex cord stromal tumors. In addition, SOX17 was expressed in vascular endothelial cells and was positive in all tested angiosarcomas. In summary, our results demonstrate that SOX17 is a sensitive and specific marker for ovarian nonmucinous carcinomas and endometrial carcinomas. For ovarian germ cell tumors and angiosarcomas, SOX17 demonstrates higher specificity than PAX8, with comparable sensitivity. Furthermore, SOX17 positivity in endothelial cells serves as an internal positive control, making it an excellent marker.

Multi-institutional Assessment of Pathologist Scoring HER2 Immunohistochemistry.

The HercepTest was approved 20 years ago as the companion diagnostic test for trastuzumab in human epidermal growth factor 2 (HER2) or ERBB2 gene-amplifiedoverexpressing breast cancers. Subsequent HER2 immunohistochemistry (IHC) assays followed, including the now most common Ventana 4B5 assay. Although this IHC assay has become the clinical standard, its reliability, reproducibility, and accuracy have largely been approved and accepted on the basis of concordance among small numbers of pathologists without validation in a real-world setting. In this study, we evaluated the concordance and interrater reliability of scoring HER2 IHC in 170 breast cancer biopsies by 18 breast cancer-specialized pathologists from 15 institutions. We used the Observers Needed to Evaluate Subjective Tests method to determine the plateau of concordance and the minimum number of pathologists needed to estimate interrater agreement values for large numbers of raters, as seen in the real-world setting. We report substantial discordance within the intermediate categories (<1% agreement for 1 and 3.6% agreement for 2) in the 4-category HER2 IHC scoring system. The discordance within the IHC 0 cases is also substantial with an overall percent agreement (OPA) of only 25% and poor interrater reliability metrics (0.49 Fleiss kappa, 0.55 intraclass correlation coefficient). This discordance can be partially reduced by using a 3-category system (28.8% vs 46.5% OPA for 4-category and 3-category scoring systems, respectively). Observers Needed to Evaluate Subjective Tests plots suggest that the OPA for the task of determining a HER2 IHC score 0 from not 0 plateaus statistically around 59.4% at 10 raters. Conversely, at the task of scoring HER2 IHC as 3 or not 3 pathologists concordance was much higher with an OPA that plateaus at 87.1% with 6 raters. This suggests that legacy HER2 IHC remains valuable for finding the patients in whom the ERBB2 gene is amplified but unacceptably discordant in assigning HER2-low or HER2-negative status for the emerging HER2-low therapies.

Interobserver Variation in the Assessment of Immunohistochemistry Expression Levels in HER2-Negative Breast Cancer Can We Improve the Identification of Low Levels of HER2 Expression by Adjusting the Criteria An International Interobserver Study.

The classification of human epidermal growth factor receptor 2 (HER2) expression is optimized to detect HER2-amplified breast cancer (BC). However, novel HER2-targeting agents are also effective for BCs with low levels of HER2. This raises the question whether the current guidelines for HER2 testing are sufficiently reproducible to identify HER2-low BC. The aim of this multicenter international study was to assess the interobserver agreement of specific HER2 immunohistochemistry scores in cases with negative HER2 results (0, 1, or 2in situ hybridization negative) according to the current American Society of Clinical OncologyCollege of American Pathologists (ASCOCAP) guidelines. Furthermore, we evaluated whether the agreement improved by redefining immunohistochemistry (IHC) scoring criteria or by adding fluorescent in situ hybridization (FISH). We conducted a 2-round study of 105 nonamplified BCs. During the first assessment, 16 pathologists used the latest version of the ASCOCAP guidelines. After a consensus meeting, the same pathologists scored the same digital slides using modified IHC scoring criteria based on the 2007 ASCOCAP guidelines, and an extra ultralow category was added. Overall, the interobserver agreement was limited (4.7% of cases with 100% agreement) in the first round, but this was improved by clustering IHC categories. In the second round, the highest reproducibility was observed when comparing IHC 0 with the ultralow12 grouped cluster (74.3% of cases with 100% agreement). The FISH results were not statistically different between HER2-0 and HER2-low cases, regardless of the IHC criteria used. In conclusion, our study suggests that the modified 2007 ASCOCAP criteria were more reproducible in distinguishing HER2-0 from HER2-low cases than the 2018 ASCOCAP criteria. However, the reproducibility was still moderate, which was not improved by adding FISH. This could lead to a suboptimal selection of patients eligible for novel HER2-targeting agents. If the threshold between HER2 IHC 0 and 1 is to be clinically actionable, there is a need for clearer, more reproducible IHC definitions, training, andor development of more accurate methods to detect this subtle difference in protein expression levels.

Serum concentrations of local anesthetics after unilateral interpectoral-pectoserratus plane block in breast cancer surgery a pharmacokinetic study.

The ultrasound-guided interpectoral-pectoserratus plane block is a fascial plane block for superficial surgery of the anterolateral chest wall. This technique involves injecting a relatively large volume of local anesthetics (typically 30 mL of 0.25%-0.50%, ie, 75-150 mg ropivacaine) underneath the major and minor pectoral muscles of the anterior thoracic wall. There is a potential risk of toxic serum concentrations of local anesthetics due to systemic absorption. 22 patients scheduled for elective unilateral breast cancer surgery were included in this study. All surgery was performed with general anesthesia and an ultrasound-guided interpectoral-pectoserratus plane block with 2.5 mgkg ropivacaine. Ten venous blood samples were collected at 0 (two samples) 10, 20, 30, 45, 60, 90 and 120 min and at 4 hours after performing the block. Free and total ropivacaine levels were measured at each time point. Albumin and alpha-1-acid-glycoprotein were measured to monitor shifts between the free and bound fraction of ropivacaine. Samples of 20 patients were analyzed. The mean dose of ropivacaine was 172.8 (22.5) mg. In 50% of the patients, the potentially toxic threshold of 0.15 µgmL free ropivacaine concentration was exceeded. Mean peak serum concentration occurred at 20 min postinjection. This pharmacokinetic study demonstrated that a 2.5 mgkg ropivacaine interpectoral-pectoserratus plane block may result in exceeding the threshold for local anesthetic systemic toxicity.

Electrochemotherapy with intravenous bleomycin for heavily pre-treated vulvar cancer patients.

The management of vulvar cancer recurrences is complicated by patients advanced age and comorbidities. Bleomycin-based electrochemotherapy is a potential treatment option in this setting. However, no data on long-term outcomes are available. Therefore, a multicenter observational study was designed to evaluate the 5-year results in these patients. Data about patients and tumor characteristics, electrochemotherapy cycles, clinical response, and follow-up were recorded. Treatment procedures were performed according to the European Standard Operating Procedures of Electrochemotherapy (ESOPE) guidelines. Response was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Fifty-one patients (mean age 82.31±7.28 years) with squamous cell vulvar cancer underwent electrochemotherapy (median number of sessions 1 range 1-4). 20 patients had complete response and 32% of these were disease-free after 2 years (median progression-free survival 16.8 months). In 13 patients with partial response the median progression-free survival was 15.36 months, while patients with stable or progressive disease showed tumor relapse after 6.95 and 3.26 months, respectively (p<0.001). Median overall survival was 18.77, 13.07, 6.73, and 11.13 months in patients with complete response, partial response, stable disease, and progressive disease, respectively (p0.001). Long-term follow-up of vulvar cancer patients showed reasonable tumor control after electrochemotherapy and improved progression-free survival and overall survival in responder subjects compared with non-responders. Further studies aimed at improving local response after electrochemotherapy are warranted. Thus, this approach represents a potential alternative for these patients.

Risks of mortality and severe coronavirus disease 19 (COVID-19) outcomes in patients with or without systemic lupus erythematosus.

We compared the outcomes of patients with or without systemic lupus erythematosus (SLE) who were diagnosed with coronavirus disease 19 (COVID-19) and evaluated factors within patients with SLE associated with severe outcomes. This retrospective cohort study used the deidentified Optum COVID-19 electronic health record dataset to identify patients with COVID-19 from 112020 to 31122020. Cases with SLE were matched with general controls at a ratio of 110 by age, sex, race and ethnicity and COVID-19 diagnosis date. Outcomes included 30-day mortality, mechanical ventilation, hospitalisation and intensive care unit admission. We evaluated the relationship between COVID-19-related outcomes and SLE using multivariable logistic regression. In addition, within SLE cases, we examined factors associated with COVID-19 related outcomes, including disease activity and SLE therapy. We included 687 patients matched with 6870 controls. Unadjusted rates of outcomes for patients with SLE were significantly worse than for matched controls including mortality (3.6% vs 1.8%), mechanical ventilation (6% vs 2.5%) and hospitalisation (31% vs 17.7%) (all p<0.001). After multivariable adjustment, patients with SLE had increased risks of mechanical ventilation (OR 1.81, 95% CI 1.16 to 2.82) and hospitalisation (OR 1.32, 95% CI 1.05 to 1.65). Among patients with SLE, severe disease activity was associated with increased risks of mechanical ventilation (OR 5.83, 95% CI 2.60 to 13.07) and hospitalisation (OR 3.97, 95% CI 2.37 to 6.65). Use of glucocorticoids, mycophenolate and tacrolimus before COVID-19 was associated with worse outcomes. Patients with SLE had increased risk of severe COVID-19-related outcomes compared with matched controls. Patients with severe SLE disease activity or prior use of corticosteroids experienced worse outcomes.

E2F1-mediated ectopic expression of PP1A promotes breast cancer progression via activation of YAP1.

Hormone receptor-positive breast cancer is the most common subtype of breast cancer. The protein phosphatase PP1A gene is described as an oncogene in several tumor types however, the biological function of PP1A in hormone receptor-positive breast cancer remains unclear. The Cancer Genome Atlas data indicates PP1A expression is upregulated in hormone receptor-positive breast cancer tissues than in normal breast tissues. We explored the biological function of PP1A in hormone receptor-positive breast cancer using MTT assays, colony formation assays, and a xenograft mouse model. The results indicated that PP1A promoted hormone receptor-positive breast cancer proliferation, both in vitro and in vivo. Mechanistically, LINC02754 recruited the binding of the transcription factor E2F1 to the PP1A promotor, thereby increasing PP1A expression. The PP1A then interacted with and dephosphorylated YAP1, resulting in YAP1 activation. The dephosphorylated YAP1 moved to the nucleus and increased the expression of the downstream oncogene CTGF, promoting hormone receptor-positive breast cancer progression. Our findings reveal the function of the LINC02754E2F1PP1AYAP1 axis in hormone receptor-positive breast cancer and provide new insight into hormone receptor-positive breast cancer progression. AVAILABILITY OF SUPPORTING DATA All data included in this study are available upon request by contact with the corresponding author.

False-Positive Nodes With Axillary Silicone Lymphadenopathy in an Oncologic Patient With a Rare Breast Cancer and Implant Rupture.

In this case, a 43-year-old woman with a rare breast tumor and a history of augmentation mammoplasty is presented. The patient arrived at the clinic reporting a palpable lump in the right mammary gland and two ipsilateral axillary nodes with pain on palpation. Mammography and ultrasound confirmed the presence of a 4 cm tumor and 2 metastatic lymph nodes of 2 cm each, histopathological diagnosis was an encapsulated papillary cancer and two siliconomas, respectively. Interestingly, these nodes were able to take up technetium 99 and methylene blue contrast media. Due to these findings, adequate patient management was carried out with a skin-sparing mastectomy and hormonal treatment with tamoxifen. This report is relevant as it shows that axillary lymphadenopathy caused by silicone must be considered in the evaluation of a patient with a cancer diagnosis and history of augmentation mammoplasty, especially breast cancer as the node siliconomas present a high risk of being considered a false positive metastasis.

HCTNet A hybrid CNN-transformer network for breast ultrasound image segmentation.

Automatic breast ultrasound image segmentation helps radiologists to improve the accuracy of breast cancer diagnosis. In recent years, the convolutional neural networks (CNNs) have achieved great success in medical image analysis. However, it exhibits limitations in modeling long-range relations, which is unfavorable for ultrasound images with speckle noise and shadows, resulting in decreased accuracy of breast lesion segmentation. Transformer can obtain sufficient global information, but it is deficient in acquiring local details and needs to be pre-trained on large-scale datasets. In this paper, we propose a Hybrid CNN-Transformer network (HCTNet) for boosting the breast lesion segmentation in ultrasound images. In the encoder of HCTNet, Transformer Encoder Blocks (TEBlocks) are designed to learn the global contextual information, which are combined with CNNs to extract features. In the decoder of HCTNet, a Spatial-wise Cross Attention (SCA) module is developed based on the spatial attention mechanism, which reduces the semantic discrepancy with the encoder. Moreover, residual connection is used between decoder blocks to make the generated features more discriminative by aggregating contextual feature maps at different semantic scales. Extensive experiments on three public breast ultrasound datasets demonstrate that HCTNet outperforms other medical image segmentation methods and the recent semantic segmentation methods on breast ultrasound lesion segmentation.

Prognostic value of KI-67 proliferation index in luminal breast cancers.

This study aimed to examine the prognostic significance of the KI-67 proliferation index, especially in breast cancer (BC) patients without HER-2 expression and no nodal involvement. The database of hormone-receptor-positive patients who underwent surgery for BC in our Surgical Oncology Clinic between 2008 and 2020 was retrospectively reviewed and recorded. Patients were categorized based on their KI-67 level, considering the cutoff value of 20%. Our study revealed that tumors with high KI-67 levels were more likely to have a more advanced histological grade (p 0.00) and size (p 0.038). In the univariant analysis, KI-67 level was effective on overall survival (p 0.044) and disease-free survival (p 0.048). However, we found that there was no independent prognostic factor in the multivariant analysis. Although the Ki-67 proliferation index does not yet have an agreed threshold value and scoring methodology, it can also be used to determine prognosis and evaluate treatment response in some patients. Este estudio tuvo como objetivo examinar la importancia pronóstica del índice de proliferación KI-67, especialmente en pacientes con cáncer de mama sin expresión de HER-2 y sin compromiso ganglionar. Se revisó y registró retrospectivamente la base de datos de pacientes con receptores hormonales positivos intervenidas de cáncer de mama en nuestra Clínica de Oncología Quirúrgica entre 2008 y 2020. Las pacientes fueron categorizadas de acuerdo con su nivel de KI-67, considerando el valor de corte del 20%. Nuestro estudio reveló que los tumores con valores elevados de KI-67 eran más propensos a tener un grado histológico (p 0.00) y un tamaño (p 0.038) más avanzados. En el análisis univariado, el nivel de KI-67 fue efectivo sobre la supervivencia global (p 0.044) y la supervivencia libre de enfermedad (p 0.048). Sin embargo, encontramos que no había ningún factor pronóstico independiente en el análisis multivariante. Aunque el índice de proliferación Ki-67 aún no tiene un valor de umbral acordado ni una metodología de puntuación, también se puede utilizar para determinar el pronóstico y evaluar la respuesta al tratamiento en algunas pacientes.

Análisis del coste directo de la atención médica y quirúrgica del cáncer de mama. Estudio comparativo entre etapas temprana y tardía en tercer nivel de atención.

Management of breast cancer is increased by late diagnoses. To analyse direct costs of breast cancer in early and advanced stage in a third level medical facility at Mexican Social Security Institute. Observational study, direct costs of care in breast cancer in initial and advanced clinical stages are compared. Variables analysed were laboratory and diagnostic imaging studies, drugs, as well as hospitalization costs. The evaluated period included from the first care to the completion of the treatment. Costs were determined according to the table of Unit Costs by Level of Medical Care for the year 2019 of the Mexican Social Security Institute. Students t test was used to determinate differences between groups, as well as descriptive statistics. The advanced stage compared to the initial stage, causes a greater number of laboratory-cabinet studies, surgeries, daybed and interconsultations. The average cost of breast cancer care per patient is $99,280.36 (US$5,230.78) and $148,023.60 (US$7,789.92) for the initial and advanced stages, respectively (p 0.024). Cost of medical attention in the initial stage is lower than that of the advanced stage. Los diagnósticos tardíos elevan los costes de atención del cáncer de mama. Analizar los costes directos de la atención del cáncer de mama en etapa temprana y avanzada en el tercer nivel de atención en el Instituto Mexicano del Seguro Social (IMSS). Estudio observacional que compara los costes directos de atención en cáncer de mama en estadios clínicos inicial y avanzado. Los datos analizados fueron estudios de laboratorio, gabinete, tratamiento y hospitalización. El tiempo evaluado incluyó desde la primera atención hasta la finalización del primer tratamiento. Se determinaron los costes de acuerdo con la tabla de Costes Unitarios por Nivel de Atención Médica para el año 2019 del IMSS. Se utilizó la prueba t de Student para diferencias entre grupos, así como estadística descriptiva. El estadio avanzado, comparado con el estadio inicial, ocasiona un número mayor de estudios de laboratorio-gabinete, cirugías, díacama e interconsultas. El coste promedio de la atención del cáncer de mama por paciente es $99,280,36 (US$5,230.78) y $148,023.60 (US$7,789.92) para los estadios inicial y avanzado, respectivamente (p 0.024). El coste de la atención médica del estadio inicial es menor que el del estadio avanzado.

Improving Uptake of Cancer Genetic Risk Assessment in a Remote Tailored Risk Communication and Navigation Intervention Large Effect Size but Room to Grow.

Cancer genetic risk assessment (CGRA) is recommended for women with ovarian cancer or high-risk breast cancer, yet fewer than 30% receive recommended genetic services, with the lowest rates among underserved populations. We hypothesized that compared with usual care (UC) and mailed targeted print (TP) education, CGRA uptake would be highest among women receiving a phone-based tailored risk counseling and navigation intervention (TCN). In this three-arm randomized trial, women with ovarian or high-risk breast cancer were recruited from statewide cancer registries in Colorado, New Jersey, and New Mexico. Participants assigned to TP received a mailed educational brochure. Participants assigned to TCN received the mailed educational brochure, an initial phone-based psychoeducational session with a health coach, a follow-up letter, and a follow-up navigation phone call. Participants average age was 61 years, 25.4% identified as Hispanic, 5.9% identified as non-Hispanic Black, and 17.5% lived in rural areas. At 6 months, more women in TCN received CGRA (18.7%) than those in TP (3% odds ratio, 7.4 95% CI, 3.0 to 18.3 TCN increased CGRA uptake in a group of geographically and ethnically diverse high-risk breast and ovarian cancer survivors. Remote personalized interventions that incorporate evidence-based health communication and behavior change strategies may increase CGRA among women recruited from statewide cancer registries.

Molecular-Guided Off-Label Targeted Therapy in a Large-Scale Precision Oncology Program.

Increasing utilization of comprehensive genomic profiling (CGP) and a growing number of targeted agents (TAs) have led to substantial improvements in outcomes among patients with cancer with actionable mutations. We sought to evaluate real-world experience with off-label TAs among Veterans who underwent CGP. The National Precision Oncology Program database and VA Corporate Data Warehouse were queried to identify patients who underwent CGP between February 2019 and December 2021 and were prescribed 1 of 73 TAs for malignancy. OncoKB annotations were used to select patients who received off-label TAs based upon CGP results. Chart abstraction was performed to review response, toxicities, and time to progression. Of 18,686 patients who underwent CGP, 2,107 (11%) were prescribed a TA and 169 (0.9%) were prescribed a total of 183 regimens containing off-label TAs for variants in 31 genes. Median age was 68 years and 83% had prior systemic therapy, with 28% receiving three or more lines. Frequency of off-label TA prescriptions was highest for patients undergoing CGP for thyroid (8.6%) and breast (7.6%) cancers. Most patients harbored alterations in Although administration of off-label TAs is infrequent after CGP, more than one quarter of treatment regimens led to response. TAs associated with level 4 annotations lead to worse outcomes than TAs bearing higher levels of evidence.

Impact of Acupuncture on Hot Flashes in Breast Cancer Patients Receiving Adjuvant Antiestrogen Therapy with Tamoxifen A Randomized Controlled Trial.

Self-Generation of Distinguishable Fluorescent Probes via a One-Pot Process for Multiple MicroRNA Detection by Liquid Chromatography.

To address the challenge of signal production and separation for multiple microRNA (miRNA) detection, in this work, a one-pot process to self-generate distinguishable fluorescent probes was developed. Based on a long and short probe amplification strategy, the generated G-quadruplex fluorescent dye-free probes can be separated and detected by a high-performance liquid chromatography-fluorescence platform. The free hairpin probes enriched in guanine with different lengths and base sequences were designed and could be opened by the target miRNAs (miRNA-10b, miRNA-21, and miRNA-210). Cleaved G-quadruplex probes with fluorescent signal could be generated in a one-pot process after a duplex-specific nuclease-based cleavage, and the detection of multiple miRNAs could be realized in one run. No solid nanomaterials were applied in the assay, which avoided the blocking of the column. Moreover, without modification of expensive fluorescein, the experimental cost was greatly reduced. The one-pot reaction process also eliminated tedious preparation steps and suggested feasibility of automation. The limits of detection of miRNA-10b, miRNA-21, and miRNA-210 were 2.19, 2.20, and 2.75 fM, respectively. Notably, this method was successfully applied to multiplex detection of miRNAs in serum samples from breast cancer patients within 30 min.

Emotional, inflammatory, and genetic factors of resilience and vulnerability to depression in patients with premenopausal breast cancer A longitudinal study protocol.

Psychosocial stress and depressive disorder have been associated with cancer as putative contributors to worse prognosis. On the other hand, cancer diagnosis is a recognised life event that can contribute to distress and depressive states. Humoral and cellular inflammation can promote depressive disorder by means of decreased monoamine synthesis, glutamate neurotoxicity, neurogenesis and neuroplasticity, dysregulated hypothalamic-pituitary-adrenal axis, and glucocorticoid resistance. This protocol objectives are to observe the interactions between psychosocial variables and biochemical and immunological biomarkers in a longitudinal, prospective design to identify inflammation-related depression endophenotypes in breast cancer patients and to understand if early diagnosed and treated depression in this population will translate in better inflammation status and better global prognosis. Prospective observational cohort, composed by 100 consecutive premenopausal patients, diagnosed with non-distant metastatic breast carcinoma and with no history of major psychopathology or other organic illness. The participants will have an in-person assessment in three different moments, along illness treatment and follow-up, with respect to cytometric, immunologic, and psychosocial parameters and will be tested for depression vulnerability and resilience inflammation-related functional genetic polymorphisms. Additionally, at years 5 and 10 post enrollment, patientsmedical records will be assessed. As a control cohort, all patients excluded due to psychiatric history or past psychiatric treatments will have their clinical records assessed at years 5 and 10 after admission. All the data will be managed with the SPSS® software. This study is an original longitudinal cohort of breast cancer premenopausal patients, with a comprehensive approach to psychosocial, clinical, inflammatory, and genetic variables. It expects to provide evidence regarding the links between genetic, cytometric, immunologic, and psychosocial factors, their potential contribution to the pathophysiology of depressive disorder, breast cancer course, progression, and prognosis. It may further contribute with data to better efficacy of the psycho-oncological interventions. National Commission of Data Protection (CNPD) 134132017 Ethics Committee of IPOP project code CI-IPOP812017.

Understanding the role of access in Hispanic cancer screening disparities.

Hispanic populations in the United States experience numerous barriers to care access. It is unclear how cancer screening disparities between Hispanic and non-Hispanic White individuals are explained by access to care, including having a usual source of care and health insurance coverage. A secondary analysis of the 2019 National Health Interview Survey was conducted and included respondents who were sex- and age-eligible for cervical (n 8316), breast (n 6025), or colorectal cancer screening (n 11,313). The proportion of ever screened and up to date for each screening type was compared. Regression models evaluated whether controlling for reporting a usual source of care and type of health insurance (public, private, none) attenuated disparities between Hispanics and non-Hispanic White individuals. Hispanic individuals were less likely than non-Hispanic White individuals to be up to date with cervical cancer screening (71.6% vs. 74.6%) and colorectal cancer screening (52.9% vs. 70.3%), but up-to-date screening was similar for breast cancer (78.8% vs. 76.3%). Hispanic individuals (vs. non-Hispanic White) were less likely to have a usual source of care (77.9% vs. 86.0%) and more likely to be uninsured (23.6% vs. 7.1%). In regressions, insurance fully attenuated cervical cancer disparities. Controlling for both usual source of care and insurance type explained approximately half of the colorectal cancer screening disparities (adjusted risk difference -8.3 -11.2 to -4.8). Addressing the high rate of uninsurance among Hispanic individuals could mitigate cancer screening disparities. Future research should build on the relative successes of breast cancer screening and investigate additional barriers for colorectal cancer screening. This study uses data from a national survey to compare cancer screening use those who identify as Hispanic with those who identify as non-Hispanic White. Those who identify as Hispanic are much less likely to be up to date with colorectal cancer screening than those who identify as non-Hispanic White, slightly less likely to be up to date on cervical cancer screening, and similarly likely to receive breast cancer screening. Improving insurance coverage is important for health equity, as is further exploring what drives higher use of breast cancer screening and lower use of colorectal cancer screening.

Integrative analyses of RNA-seq and ChIP-seq Reveal MITF as a Target Gene of TFPI-2 in MDA231 Cells.

Breast cancer is the most prevalent cancer in female patients worldwide. Tissue factor pathway inhibitor 2 (TFPI-2) is identified as an important tumor suppressor in various cancers. Recent studies have shown that TFPI-2 translocates into the nucleus, where it modulates the transcription of the matrix metalloproteinase-2 (MMP-2) gene. However, its biological role and molecular mechanisms in the progression of breast cancer remain unclear. In this study, we identified 5125 differentially expressed genes (DEGs) from RNA sequencing (RNA-seq) in TFPI-2-overexpressing MDA231 cells compared with control cells. Gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) analysis shown that cell cycle, cell differentiation, proteoglycans in cancer, and pathways associated with cancer were highly enriched in downregulated DEGs. Integration of the RNA-seq and ChIP-sequencing (ChIP-seq) data identified 73 genes directly controlled by TFPI-2 in MDA231 cells. Among them, melanocyte inducing transcription factor (MITF) gene expression was repressed by TFPI-2, which was further verified by a luciferase reporter assay and ChIP-quantitative PCR. Our study provides evidence of a novel role of TFPI-2 in human breast cancer involving targeting of the MITF.

PDQ Cancer Information Summaries

This PDQ cancer information summary has current information about the treatment of rare cancers of childhood. It is meant to inform and help patients, families, and caregivers. It does not give formal guidelines or recommendations for making decisions about health care. Editorial Boards write the PDQ cancer information summaries and keep them up to date. These Boards are made up of experts in cancer treatment and other specialties related to cancer. The summaries are reviewed regularly and changes are made when there is new information. The date on each summary (Date Last Modified) is the date of the most recent change. The information in this patient summary was taken from the health professional version, which is reviewed regularly and updated as needed, by the PDQ Pediatric Treatment Editorial Board.

Synergistic Effect of the Combined Action of Targeted and Photodynamic Therapy on HER2-Positive Breast Cancer.

Development of combined schemes for the treatment of oncological diseases is a promising strategy to improve the effectiveness of antitumor therapy. This paper shows the fundamental possibility of multiplying the antitumor effect by combining targeted and photodynamic therapy. It was demonstrated that sequential treatment of HER-2 positive breast cancer cells with the targeted toxin DARPin-LoPE and the photoactive compound photodithazine leads to a synergistic enhancement of their effect. In the future, this approach is intended to achieve the maximum therapeutic effect while minimizing the risks of negative side effects.

Effects of preoperative magnetic resonance image on survival rates and surgical planning in breast cancer conservative surgery randomized controlled trial (BREAST-MRI trial).

Breast magnetic resonance imaging (MRI) has high sensitivity in detecting invasive neoplasms. Controversy remains about its impact on the preoperative staging of breast cancer surgery. This study evaluated survival and surgical outcomes of preoperative MRI in conservative breast cancer surgery. A phase III, randomized, open-label, single-center trial including female breast cancer participants, stage 0-III disease, and eligible for breast-conserving surgery. We compared the role of including MRI in preoperative evaluation versus radiologic exam routine with mammography and ultrasound in breast cancer conservative candidates. The primary outcome was local relapse-free survival (LRFS), and secondary outcomes were overall survival (OS), mastectomy rate, and reoperation rate. 524 were randomized to preoperative MRI group (n 257) or control group (n 267). The survival analysis showed a 5.9-years LRFS of 99.2% in MRI group versus 98.9% in control group (HR 0.72 95% CI 0.12-4.28 p 0.7) and an OS of 95.3% in the MRI group versus 96.3% in the control group (HR 1.37 95% CI 0.59-3.19 p 0.8). Surgical management changed in 21 ipsilateral breasts in the MRI group 21 (8.3%) had mastectomies versus one in the control group. No difference was found in reoperation rates, 22 (8.7%) in the MRI group versus 23 (8.7%) in the control group (RR 1.002 95% CI 0.57-1.75 p 0.85). Preoperative MRI increased the mastectomy rates by 8%. The use of preoperative MRI did not influence local relapse-free survival, overall survival, or reoperation rates.

Communication between mothers with breast cancer and minor children a qualitative systematic review and meta-synthesis.

Both women with breast cancer and their minor children were affected by a breast cancer diagnosis. The purpose of this review was to synthesize the evidence from qualitative studies on illness-related communication between mothers with breast cancer and their minor children from mothers perspectives. A thorough systematic review and meta-synthesis of qualitative studies was conducted. English articles published prior to 6 November 2021 were searched from five databases, including PubMed MEDLINE, EMBASE, Web of Science, CINAHL, and PsycINFO. After screening the titles, abstracts, and full texts, seven articles were finally included in the quality appraisal and meta-aggregation. Four synthesized findings were derived from seven articles, including disclosure dilemma, factors impacting disclosure, methods of communication, and information needs. This systematic review offered insight into the communication between mothers with breast cancer and their minor children. Various factors influenced the decision-making process on illness-related disclosure, as well as the methods and contents of the communication. Future studies should be undertaken to explore the common model shared by mothers and children who have had comparable experiences, as well as to completely analyze the differences between different cultures in this topic.

Beyond Antiresorptive Activity Risedronate-Based Coordination Complexes To Potentially Treat Osteolytic Metastases.

Coordination of clinically employed bisphosphonate, risedronate (RISE), to bioactive metals, Ca

Dosimetric evaluation of the benefit of deep inspiration breath hold (DIBH) for locoregional irradiation of right breast cancer with volumetric modulated arctherapy (VMAT).

Right-lateralized cardiac substructures can be substantially exposed during right breast cancer (R-BC) radiotherapy. The cardiac benefit of deep inspiration breath hold (DIBH) is established in combination with volumetric modulated arctherapy (VMAT) for left breast cancer with regional node irradiation but is unknown for R-BC. This study evaluated the dosimetric benefit of DIBH for locoregional irradiation of R-BC with VMAT. All patients treated for R-BC with adjuvant locoregional DIBH-VMAT in the Department of Radiation Oncology of the Institut Curie (Paris, France) until December 2022 were included, corresponding to 15 patients. FB- and DIBH-VMAT plans were compared both for a normofractionated regimen (50 Gy25fx) used for treatment and a replanned hypofractionated regimen (40 Gy15fx). Dose to the heart, cardiac substructures (sinoatrial node (SAN), atrio-ventricular node (AVN), right coronary artery, left anterior descending coronary artery, left ventricle), ipsilateral lung and liver were retrieved and compared. Mean heart dose (MHD) was 3.33 Gy with FB vs. 3.10 Gy with DIBH on normofractionated plans ( Adding DIBH to efficient cardiac-sparing radiotherapy techniques, such as VMAT, is not justified in the general case for locoregional R-BC irradiation. Specific R-BC patient subpopulations who could benefit from additional DIBH combination with locoregional VMAT are yet to be identified.

Design, Synthesis, and Biological Activity of Marinacarboline Analogues as STAT3 Pathway Inhibitors for Docetaxel-Resistant Triple-Negative Breast Cancer.

Metastatic triple-negative breast cancer (mTNBC) is a fatal type of breast cancer (BC), and signal transducer and activator of transcription 3 (STAT3) has emerged as an effective target for mTNBC. In the present study, compound

MED27 plays a tumor-promoting role in breast cancer progression by targeting KLF4.

Our study found that MED27 was highly expressed in breast cancer and promoted breast cancer development, especially its metastasis and stemness maintenance, by targeting KLF4 both in vitro and in vivo. Mechanistically, MED27 transcriptionally activated KLF4 by binding to its promoter region in breast cancer cells. MED27 silencing sensitized breast cancer cells to epirubicin therapy. The high expression of MED27 and KLF4 alone or both was positively correlated with the differentiation status of cancer cells and predicted poor prognosis of breast cancer patients. All these findings provide the potential of developing MED27KLF4 signaling axis as the cascade candidate therapeutic targets and prognosis biomarkers in breast cancer.

Light Pareto robust optimization for IMRT treatment planning.

Robust optimization (RO) has been proposed to mitigate breathing motion uncertainty during treatment in intensity-modulated radiation therapy (IMRT) planning for breast or lung cancer. RO is a pessimistic approach that implicitly trades off average-case for worst-case treatment plan quality. Pareto robust optimization (PRO) provides amechanism for improving non-worst-case plan outcomes, but often remains overly-conservative in the average case. The goal of this study is to characterize the trade-off between the optimality of robust IMRT plans in the worst case and the treatment quality in non-worst-case realizations of breathing motion. We provide a light Pareto robust optimization (LPRO) method for IMRT and test its clinical viability for improving the average-case plan quality while preserving robustness, in comparison to RO and PRO plans. Five clinical left-sided breast cancer patients were included in the study, each with an associated 4D-CT dataset approximating their breathing cycle. Using simulation, 50 different breathing patterns were generated for each patient. A first-stage optimization was solved with the objective of cardiac sparing while ensuring robustness on the target dose under breathing uncertainty. Next, a second-stage objective of overdose minimization was considered to improve plan quality in a controlled LPRO framework. For the simulated breathing scenarios, the trade-off between loss of average cardiac sparing at worst-case and the overdose to the breast was quantified by calculating theaccumulated dose for each plan in each breathing scenario. Finally, the RO, PRO and LPRO plans were each evaluated using eight clinical dose-volume criteria on the target and organs at risk. The LPRO models allowed for significantly sharper dose falloffs in the expected dose instances, relative to both RO and PRO models. Plans began looking valid for delivery with average allowances of as little as 0.1 Gy additional dose to the heart, and most patients experienced diminishing returns beyond 0.2 Gy. Without sacrificing robustness, the LPRO approach produces viable plans with true total-target irradiation. Furthermore, the plans produced were able to reduce the non-worst-case downside typical of RO, without the characteristic overdosing or average-case pessimism seen in prior models. This article is protected by copyright. All rights reserved.

Cancer referrals at African Inland Church Kijabe Hospital, Kiambu County (2014-2020) and the impact of COVID-19.

In Kenya, cancer is the third leading cause of death. The African Inland Church Kijabe Hospital (AICKH) is a level 4 missionary hospital. The hospital serves the Kenyan population in many areas, including cancer care, and some of these services were affected during the coronavirus disease 2019 (COVID-19) pandemic. We aimed to leverage a recently established hospital-based cancer registry of patients treated at AICKH between 2014 and 2020 to describe the cancer cases and patient referral patterns seen at AICKH during the COVID-19 pandemic in 2020. A cross-sectional retrospective survey was conducted through medical records abstraction in the surgery, breast clinic, palliative care and pathology departments. A total of 3279 cases were included in the study, with females accounting for 58.1% of the cases. The top-three cancers overall were breast (23.0%), oesophagus (20.5%) and prostate (8.6%). There was a minimal increase in the number of cancer cases in 2020 (1.7%) compared with 2019, with an increase of 19.3% in 2019 compared with 2018. In conclusion, AICKH is one of the few hospitals in Kenya where a large number of cancer patients seek healthcare, and referral of cancer cases changed in 2020, which may be due to the COVID-19 pandemic. Future efforts can leverage this registry to determine the impacts of cancer diagnosis and treatment on survival outcomes.

YB-1 Expression Is Associated with Lymph Node Metastasis and Drug Resistance to Adriamycin in Breast Cancer.

Breast cancer (BC) is the most common malignant tumor among females. Although there are multiple treatments for breast cancer, many patients still face the dilemma of drug resistance after multiline treatment. It would be greatly helpful for clinical work to identify additional and improved prognostic predictors. Y-box binding protein-1 (YB-1) is a member of the cold shock protein family, and patients with overexpression of YB-1 have a worse prognosis. This study collected 48 specimens from 48 patients with breast cancer and analyzed the clinicopathological characteristics of the patients. Immunohistochemistry, immunofluorescence, cell viability analysis, tumor spheroid formation and cell morphology, cell invasion, cycle analysis, qRT-PCR, Western blot, and tumorigenicity in BALBc nude mice were performed to verify the results. We found that patients with overexpression of YB-1 were related to lymph node metastasis and the patients age tended to be young. Because of the short follow-up time, a survival analysis could not be performed. Based on the results of in vitro and in vivo experiments, this study indicated that breast cancer cells with overexpression of YB-1 had stronger proliferation, migration, and invasion abilities than cells with low expression of YB-1. Compared with cells with low expression of YB-1, the proliferation, migration, and invasion abilities of YB-1 overexpressed cells were not significantly affected by adriamycin. This suggested that breast cancer cells with overexpression of YB-1 were resistant to adriamycin. Therefore, YB-1 is associated with lymph node metastasis of breast cancer cell. YB-1 could be a prognostic, predictive factor and a novel therapeutic target of BC.

Association of Enolase-1 with Prognosis and Immune Infiltration in Breast Cancer by Clinical Stage.

Enolase-1 (ENO1) plays a key role in malignancies. Previous studies on the association between ENO1 expression and breast cancer prognosis had yielded inconsistent results. In the present study, we assessed the prognostic effect of ENO1 in breast cancer using Guangzhou Breast Cancer Study (GZBCS) cohort with full consideration of the potential confounders and the modification effects. The results were further validated in the TCGA-BRCA cohort and explained by tumor immunity. ENO1 protein expressions were evaluated by immunohistochemistry in tissue microarrays from 961 patients with primary invasive breast cancer. Chi-square tests were used to assess the association of ENO1 levels with the patients characteristics. Cox regression models were applied to assess the prognostic effects. The TCGA-BRCA cohort was utilized to validate the results and explore the potential mechanisms. The immune infiltration was determined using the CIBERSORT and ssGSEA algorithms the correlation between ENO1 expression and the abundance of tumor-infiltrating immune cells (TIICs) and scores of immune-related functions was evaluated by Wilcoxon signed-rank tests and Spearmans rank test. ENO1 protein expression exerted a protective effect on OS in stage III patients (HR0.58, 95% CI 0.35-0.96) but not in stage III patients (HR1.42, 95% CI 0.81-2.49, A higher expression of ENO1 was associated with a better prognosis only in early-stage breast cancer, which may be related to the different effects of ENO1 on immune infiltration, suggesting that ENO1 may be a promising target for precision immunotherapy in breast cancer.

A novel gene signature related to oxidative stress predicts the prognosis in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is considered to be related to the worse prognosis, which might in part be attributed to the early recurrence and metastasis, compared with other type of kidney cancer. Oxidative stress refers to an imbalance between production of oxidants and antioxidant defense. Accumulative studies have indicated that oxidative stress genes contribute to the tumor invasion, metastasis and drug sensitivity. However, the biological functions of oxidative stress genes in ccRCC remain largely unknown. In this study, we identified 1,399 oxidative stress genes from GeneCards with a relevance score ≥7. Data for analysis were accessed from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) database, and were utilized as training set and validation set respectively. Univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox were employed to construct a prognostic signature in ccRCC. Finally, a prognostic signature including four different oxidative stress genes was constructed from 1,399 genes, and its predictive performance was verified through Kaplan-Meier survival analysis and the receiver operating characteristic (ROC) curve. Interestingly, we found that there was significant correlation between the expression of oxidative stress genes and the immune infiltration and the sensitivity of tumor cells to chemotherapeutics. Moreover, the highest hazard ratio gene urocortin (

The Practice and Willingness of Women Towards Opportunistic Screening for Breast and Cervical Cancers in Sichuan Province, China A Cross-Sectional Study.

To understand the practices and willingness of Chinese women to undergo opportunistic screening for breast cancer (BC) and cervical cancer (CC). From July to August 2021, a cross-sectional study of 1446 women from six cities in Sichuan Province, China, was conducted. A questionnaire was used to investigate practices, willingness, and barriers to opportunistic screening for BC and CC. Furthermore, potential factors for opportunistic screening willingness were analyzed using the chi-squared test and logistic regression. During their lifetime, 312 (21.6%) and 388 (26.8%) women had undergone opportunistic screening for BC and CC, respectively. There were 1069 (73.9%) women willing to accept physician-recommended screening during a medical visit, while 835 (57.7%) were willing to have a voluntary screening at a healthcare institution. The main barriers to reluctance to participate in physician-recommended and voluntary screenings were no symptoms hence, no need for screening and unwillingness or difficulty in paying screening cost. Ethnic minorities, lower education levels, and menopause were inversely associated, whereas awareness of the screening methods and eligibility for screening were positively associated with physician-recommended and voluntary screenings ( BC and CC opportunistic screening rates in Sichuan Province were low. The willingness to undergo physician-recommended screening was high, while that towards individual initiative screening was low. Public health education should be strengthened to increase cancer prevention awareness and knowledge of cancer screening, especially for women with low education, ethnic minorities, and post-menopause, for whom tailored interventions are suggested. In addition, novel ways of sharing screening costs need to be explored.

Ultralow Limit Detection of Soluble HER2 Biomarker in Serum with a Fiber-Optic Ball-Tip Resonator Assisted by a Tilted FBG.

An optical-fiber biosensor has been developed for the detection of the breast cancer biomarker soluble human epidermal growth factor receptor-2 (sHER2). The sensor was fabricated by combining a tilted fiber Bragg grating (TFBG) with a ball resonator, allowing us to achieve an excellent sensitivity compared to other optical-fiber-based sensors. The sensor exhibits a resonance comb excited by the TFBG and the spectral profile of the ball resonator. The detection of sHER2 at extremely low concentrations was carried out by tracking the amplitude change of selected resonances. The therapeutic anti-HER2 monoclonal antibody Trastuzumab has been used to functionalize the biosensor with silane surface chemistry. The sensor features a sensitivity of 4034 dBRIU with a limit of detection (LoD) in buffer and in a 110 diluted serum of 151.5 agmL and 3.7 pgmL, respectively. At relatively high protein concentrations (64 ngmL) binding to sHER (7.36 dB) as compared to control proteins (below 0.7 dB) attested the high specificity of sHER2 detection.

Mainstream genetic testing for high-grade ovarian, tubal and peritoneal cancers A tertiary referral centre experience.

Fifteen percent of ovarian, tubal, and peritoneal (OTP) invasive epithelial cancers are linked to an underlying heritable pathogenic variant (PV) in the BRCA12 cancer susceptibility genes. Identifying a PV has management implications for an affected individual and relatives. Cancer team-facilitated genetic testing (mainstreaming) aims to provide equitable systematic access to genetic testing for appropriate patients. To evaluate a multi-disciplinary team (MDT)-led mainstream germline genetic testing program for OTP cancer at a tertiary referral centre. We conducted a retrospective review of our MDT-led mainstream genetic testing program initiated in June 2017. We included all patients diagnosed with OTP cancer registered with the hospital gynaecological oncology MDT from program initiation to December 2020. Patients were considered eligible for testing if they were diagnosed with a high-grade epithelial OTP AND ≤70 years, OR if >70 with a firstsecond degree relative with breast andor ovarian cancer OR Jewish ancestry. Of 205 women diagnosed with high-grade epithelial OTP cancer, 140 were eligible for mainstreaming. Eight-five percent were mainstreamed, with the gynae-oncologists facilitating 64.5% of tests. The overall PV detection rate in BRCA12 was 10.1% (BRCA1 n 9, BRCA2 n 3). The median turnaround time (TAT) was 44.5 days (range 16-118). All women with PV were referred to the Familial Cancer Service for further assessment and five (of six eligible 83%) were subsequently treated with polyadenosine diphosphate ribose polymerase inhibitors. Cascade testing was undertaken in 75% of families with a mean of three relatives tested per proband. Mainstreamed genetic testing is feasible, with an acceptable TAT, ensuring adequate opportunity to inform treatment decisions. Tumour testing and inclusion of moderate-risk cancer predisposition genes in mainstreaming represent potential pathways that will require further exploration.

The activation of EP300 by F11R leads to EMT and acts as a prognostic factor in triple-negative breast cancers.

Cancer progression is influenced by junctional adhesion molecule (JAM) family members. The relationship between JAM family members and different types of cancer was examined using The Cancer Genome Atlas dataset. mRNA levels of the F11R (F11 receptor) in tumours were inversely correlated to the expression of JAM-2 and JAM-3. This relationship was unique to breast cancer (BCa) and was associated with poor prognosis (p 0.024, hazard ratio 1.44 1.05-1.99). A 50-gene molecular signature (prediction analysis of microarray 50) was used to subtype BCa. F11R mRNA expression significantly increased in human epidermal growth factor receptor 2 (HER2)-enriched (p 0.0035) and basal-like BCa tumours (p 0.0005). We evaluated F11R protein levels in two different compositions of BCa subtype patient tissue array cohorts to determine the relationship between BCa subtype and prognosis. Immunohistochemistry staining revealed that a high F11R protein level was associated with poor overall survival (p < 0.001 Taipei Medical University TMU cohort, p < 0.001 Kaohsiung Veterans General Hospital KVGH cohort) or disease-free survival (p < 0.001 TMU cohort, p 0.034 KVGH cohort) in patients with BCa. Comparison of F11R levels in different subtypes revealed the association of poor prognosis with high levels of F11R among luminal (p < 0.001 TMU cohort, p 0.027 KVGH cohort), HER2 positive (p 0.018 TMU cohort, p 0.037 KVGH cohort), and triple-negative (p 0.013 TMU cohort, p 0.037 KVGH cohort) BCa. F11R-based RNA microarray analysis and Ingenuity Pathway Analysis were successful in profiling the detailed gene ontology of triple-negative BCa cells regulated by F11R. The EP300 transcription factor was highly correlated with F11R in BCa (R 0.51, p < 0.001). By analysing these F11R-affected molecules with the L1000CDs datasets, we were able to predict some repurposing drugs for potential application in F11R-positive BCa treatment.

Biodegradable functionalized magnetite nanoparticles as binary-targeting carrier for breast carcinoma.

In this study, Superparamagnetic magnetite nanoparticles (SPMNPs) are used in a new way as direct nanocarrier for Doxorubicin hydrochloride (DOX) via the functionalization of their surface with tri-sodium citrate through ligand exchange to conjugate DOX with imine bond to form tri-sodium citrate functionalized magnetite loaded DOX nanoparticles (DOXCit-MNPs). The DOXCit-MNPs were coated with chitosan to form chitosan coated citrate functionalized magnetite loaded DOX nanoparticles (CsDOXCit-MNPs) to offer biodegradability and pH-sensitive drug release features. The Fourier transform infrared spectroscopy (FTIR) analysis confirmed functionalization of SPMNPs, DOX-conjugation, and chitosan coating. The trans electron microscopy (TEM) show spherical nanostructures with average size 40 nm for coated nanocarriers. The saturation magnetization value of carrier was 59 emug.The in-vitro release of DOX from the chitosan coated tri-sodium citrate functionalized magnetite loaded DOX nanoparticles (CsDOXCit-MNPs) was studied to be 75% at pH 5.5 and 28.6% at pH 7.4 which proves the pH sensitivity of encapsulated CsDOXCit-MNPs. The effect of CsDOXCit-MNPs toward Human Breast Cancer Cell lines (MCF7) was studied and found to be 76% without magnet and 98% with external magnet after 72 h. With increasing DOX concentration and treatment time, the cell inhibition (IR%) of DOX solution and CsDOX-Cit-MNPs suspension to all cells is increased. CsDOXCit-MNPs showed sustained release and good inhibition to cancer cells and offer a protective mode for normal cells (WISH) compared to the free DOX.

Role of breast cancer screening in the overdiagnosis of thyroid cancer results from a cross-sectional nationwide survey.

South Korea has the highest incidence of thyroid cancer worldwide, raising questions regarding the possibility of overdiagnosis. Examining the factors affecting thyroid cancer screening is crucial in elucidating the reasons for this unusually high incidence of thyroid cancer. Therefore, in the present study, we investigated the association between breast cancer screening and thyroid cancer screening to determine the potential role of breast cancer screening in the overdiagnosis of thyroid cancer in South Korea. We analyzed the data of women aged > 30 years who were enrolled in the 2014 Korean National Cancer Screening Survey. Self-reported breast cancer screening behavior was categorized as follows no screening, mammography only, ultrasonography only, and both ultrasonography and mammography. Thyroid cancer screening behavior was categorized as follows those who had or had not undergone ultrasonography screening. Logistic regression analysis was used to examine the associations between breast and thyroid cancer screening behaviors. Of the 2270 participants, a total of 569 (25.1%) were screened for thyroid cancer. Those who underwent only mammography, only ultrasonography, or both mammography and ultrasonography were more likely to be screened for thyroid cancer than those who did not undergo breast cancer screening (odds ratio OR 1.47, 95% confidence interval CI 1.06-2.04 OR 2.71, 95% CI 1.83-4.02 OR 2.75, 95% CI 1.99-3.80, respectively). Our findings indicate that thyroid cancer screening in Korea is likely to be performed on an opportunistic basis. Therefore, a nationwide public health and medical initiative is needed to curb the unnecessary use of thyroid screening in the asymptomatic general population.

DNA methylation in peripheral blood leukocytes for the association with glucose metabolism and invasive breast cancer.

Insulin resistance (IR) is a well-established factor for breast cancer (BC) risk in postmenopausal women, but the interrelated molecular pathways on the methylome are not explicitly described. We conducted a population-level epigenome-wide association (EWA) study for DNA methylation (DNAm) probes that are associated with IR and prospectively correlated with BC development, both overall and in BC subtypes among postmenopausal women. We used data from Womens Health Initiative (WHI) ancillary studies for our EWA analyses and evaluated the associations of site-specific DNAm across the genome with IR phenotypes by multiple regressions adjusting for age and leukocyte heterogeneities. For our analysis of the top 20 IR-CpGs with BC risk, we used the WHI and the Cancer Genomic Atlas (TCGA), using multiple Cox proportional hazards and logit regressions, respectively, accounting for age, diabetes, obesity, leukocyte heterogeneities, and tumor purity (for TCGA). We further conducted a Gene Set Enrichment Analysis. We detected several EWA-CpGs in TXNIP, CPT1A, PHGDH, and ABCG1. In particular, cg19693031 in TXNIP was replicated in all IR phenotypes, measured by fasting levels of glucose, insulin, and homeostatic model assessment-IR. Of those replicated IR-genes, 3 genes (CPT1A, PHGDH, and ABCG1) were further correlated with BC risk and 1 individual CpG (cg01676795 in POR) was commonly detected across the 2 cohorts. Our study contributes to better understanding of the interconnected molecular pathways on the methylome between IR and BC carcinogenesis and suggests potential use of DNAm markers in the peripheral blood cells as preventive targets to detect an at-risk group for IR and BC in postmenopausal women.

LINC00478-derived novel cytoplasmic lncRNA LacRNA stabilizes PHB2 and suppresses breast cancer metastasis via repressing MYC targets.

Metastasis is the predominant cause of mortality in patients with breast cancer. Long noncoding RNAs (lncRNAs) have been shown to drive important phenotypes in tumors, including invasion and metastasis. However, the lncRNAs involved in metastasis and their molecular and cellular mechanisms are still largely unknown. The transcriptional and posttranscriptional processing of LINC00478-associated cytoplasmic RNA (LacRNA) was determined by RT-qPCR, semiquantitative PCR and 53 RACE. Paired-guide CRISPRcas9 and CRISPRdead-Cas9 systems was used to knock out or activate the expression of LacRNA. Cell migration and invasion assay was performed to confirm the phenotype of LacRNA. Tail vein model and mammary fat pad model were used for in vivo study. The LacRNA-PHB2-cMyc axis were screened and validated by RNA pulldown, mass spectrometry, RNA immunoprecipitation and RNA-seq assays. Here, we identified a novel cytoplasmic lncRNA, LacRNA (LINC00478-associated cytoplasmic RNA), derived from nucleus-located lncRNA LINC00478. The nascent transcript of LINC00478 full-length (LINC00478FL) was cleaved and polyadenylated, simultaneously yielding 5 ends stable expressing LacRNA, which is released into the cytoplasm, and long 3 ends of nuclear-retained lncRNA. LINC004783RNA was rapidly degraded. LacRNA significantly inhibited breast cancer invasion and metastasis in vitro and in vivo. Mechanistically, LacRNA physically interacted with the PHB domain of PHB2 through its 61-140-nt region. This specific binding affected the formation of the autophagy degradation complex of PHB2 and LC3, delaying the degradation of the PHB2 protein. Unexpectedly, LacRNA specifically interacted with PHB2, recruited c-Myc and promoted c-Myc ubiquitination and degradation. The negatively regulation of Myc signaling ultimately inhibited breast cancer metastasis. Furthermore, LacRNA and LacRNA-mediated c-Myc signaling downregulation are significantly associated with good clinical outcomes, take advantage of these factors we constructed a prognostic predict model. Therefore, our findings propose LacRNA as a potential prognostic biomarker and a new therapeutic strategy.

Colorectal cancer survivors long-term recollections of their illness and therapy up to seven years after enrolment into a randomised controlled clinical trial.

As a consequence of effective treatment procedures, the number of long-term survivors of colorectal cancer is ever increasing. Adopting the method of a previous study on breast cancer patients, the goal of the present research was to investigate colorectal cancer patients recollections of their illness and treatment experiences up to seven years after they have been enrolled in a randomised controlled clinical trial on the direct improvement of quality of life (RCT DIQOL). Colorectal cancer survivors in Bavaria, Germany were mailed a questionnaire on average 78·3 months after the start of their therapy and enrolment into RCT DIQOL. The questionnaire enquired about their worst experience during the colorectal cancer episode, positive aspects of the illness, and any advice they would give to newly diagnosed patients. Patient responses were categorised by two independent raters and cross-checked by a third independent rater. Frequencies of these categories were then quantitatively analysed using descriptive statistics. Of 146 remaining survivors initially enrolled in RCT DIQOL, 96 (66%) returned the questionnaire. The majority (33%) of statements regarding the worst experience was referring to psychological distress, followed by indigestion and discomfort during defecation (17%), and cancer diagnosis (16%). Among survivors with history of a stoma, the majority (36%) regarded stoma as their worst experience. With 45%, change in life priorities has been the most frequent positive category before support by physicians nurses (25%). 43% of the survivors deemed fighting spirit as most important advice to overcome the disease. Even after many years, colorectal cancer survivors clearly remember experiences from the time of their illness. Echoing the results of the previous breast cancer survivors study, psychological distress, change in life priorities and fighting spirit emerged as prominent concepts. In addition, some aspects like the impact of a stoma are of specific importance for colorectal cancer survivors. These findings can be used to inform programmes to improve patient- and quality of life centred aftercare of tumour patients. NCT04930016, date of registration 18.06.2021.

Phosphorylation of USP29 by CDK1 Governs TWIST1 Stability and Oncogenic Functions.

Triple-negative breast cancer (TNBC) is a highly lethal malignancy with limited therapy options. TWIST1, a key transcriptional factor of epithelial-mesenchymal transition (EMT), contributes to self-renewal of cancer stem-like cells (CSCs), chemo-resistance, metastasis, and TNBC-related death. However, the mechanism by which TWIST1 is deregulated in TNBC remains elusive. Here, USP29 is identified as a bona fide deubiquitinase of TWIST1. The deubiquitination of TWIST1 catalyzed by USP29 is required for its stabilization and subsequent EMT and CSC functions in TNBC, thereby conferring chemotherapeutic resistance and metastasis. Furthermore, the results unexpectedly reveal that CDK1 functions as the direct USP29 activator. Mechanistically, CDK1-mediated phosphorylation of USP29 is essential for its deubiquitinase activity toward TWIST1 and TWIST1 driven-malignant phenotypes in TNBC, which could be markedly mitigated by the genetic ablation or pharmacological inhibition of CDK1. Moreover, the histological analyses show that CDK1 and USP29 are highly upregulated in TNBC samples, which positively correlate with the expression of TWIST1. Taken together, the findings reveal a previously unrecognized tumor-promoting function and clinical significance of the CDK1-USP29 axis through stabilizing TWIST1 and provide the preclinical evidence that targeting this axis is an appealing therapeutic strategy to conquer chemo-resistance and metastasis in TNBC.

The association between shift work and the incidence of reflux esophagitis in Korea a cohort study.

Shift work has adverse health effects such as diabetes, cardiovascular disease, sleep disturbance, depression, and breast cancer. Gastro-esophageal reflux disease (GERD) results in lesions such as reflux esophagitis (RE) and Barretts esophagus. This study investigated the association between shift work and RE. A cohort study was conducted with 140,553 participants who were followed up at least once from 2012 to 2018. Type of working and shift types were collected using standardized questionnaires. Esophagogastroduodenoscopy (EGD) was performed by experienced endoscopists who were blinded to the aims of this study. According to the Los Angeles classification, RE was categorized based on the extent of esophageal mucosal breaks. During the 469,217.2 person-years of follow-up, 35,185 participants developed incident cases of RE. The multivariable adjusted hazard ratio (95% confidence intervals) for incident cases comparing shift work to fixed day work was 1.09 (1.04-1.13). This association was more strongly observed in the younger age group (18-39 years old) and the female group. In conclusion, shift work was significantly associated with the incidence of RE. Particularly, the results were more significant in the younger and female groups.

Ki67 increase after core needle biopsy associated with worse disease outcome in HER2-negative breast cancer patients.

Ki67 would change after core needle biopsy (CNB) in invasive breast cancer. However, whether Ki67 alteration (ΔKi67) influences disease outcomes remains unclear. Here we aim to evaluate the prognostic value of ΔKi67. Patients with paired CNB and open excision biopsy (OEB) samples between January 2009 and June 2016 were retrospectively analyzed. ΔKi67 was calculated as the absolute difference between Ki67 level in CNB and OEB samples, and the median value of 5% was adopted to category patients into high- and low ΔKi67 groups. Disease-free survival (DFS) and overall survival (OS) were compared between different ΔKi67 groups. Overall, 2173 invasive breast cancer patients were included. Median Ki67 was higher in OEB than CNB samples 25.00% versus 20.00% (P < 0.001). Axillary nodal status, STI, histological grading, and molecular subtype were independently associated with ΔKi67 (P < 0.05). In the whole population, patients with low ΔKi67 showed superior 5-year DFS (89.6% vs 87.0%, P 0.026), but similar OS (95.8% vs 94.3%, P 0.118) compared to those with high ΔKi67. HER2 status at surgery was the only significant factor interacting with ΔKi67 on both DFS (P 0.026) and OS (P 0.007). For patients with HER2-negative disease, high ΔKi67 was associated with worse 5-year DFS (87.2% vs 91.2%, P 0.004) as well as impaired 5-year OS (93.9% vs 96.8%, P 0.010). ΔKi67 had no significant impact on survival of HER2-positive patients. Ki67 increase after CNB was significantly associated with worse disease outcomes in HER2-negative, but not in HER2-positive patients, which warrants further study.

Immunotherapy in breast cancer an overview of current strategies and perspectives.

Recent progress in immunobiology has led the way to successful host immunity enhancement against breast cancer. In triple-negative breast cancer, the combination of cancer immunotherapy based on PD-1PD-L1 immune checkpoint inhibitors with chemotherapy was effective both in advanced and early setting phase 3 clinical trials. These encouraging results lead to the first approvals of immune checkpoint inhibitors in triple-negative breast cancer and thus offer new therapeutic possibilities in aggressive tumors and hard-to-treat populations. Furthermore, several ongoing trials are investigating combining immunotherapies involving immune checkpoint inhibitors with conventional therapies and as well as with other immunotherapeutic strategies such as cancer vaccines, CAR-T cells, bispecific antibodies, and oncolytic viruses in all breast cancer subtypes. This review provides an overview of immunotherapies currently under clinical development and updated key results from clinical trials. Finally, we discuss the challenges to the successful implementation of immune treatment in managing breast cancer and their implications for the design of future clinical trials.

VPA mediates bidirectional regulation of cell cycle progression through the PPP2R2A-Chk1 signaling axis in response to HU.

Cell cycle checkpoint kinases play a pivotal role in protecting against replicative stress. In this study, valproic acid (VPA), a histone deacetylase inhibitor (HDACi), was found to promote breast cancer MCF-7 cells to traverse into G2M phase for catastrophic injury by promoting PPP2R2A (the B-regulatory subunit of Phosphatase PP2A) to facilitate the dephosphorylation of Chk1 at Ser317 and Ser345. By contrast, VPA protected normal 16HBE cells from HU toxicity through decreasing PPP2R2A expression and increasing Chk1 phosphorylation. The effect of VPA on PPP2R2A was at the post-transcription level through HDAC12. The in vitro results were affirmed in vivo. Patients with lower PPP2R2A expression and higher pChk1 expression showed significantly worse survival. PPP2R2A D197 and N181 are essential for PPP2R2A-Chk1 signaling and VPA-mediated bidirectional effect on augmenting HU-induced tumor cell death and protecting normal cells.

Urban-Rural Disparity in Birth Cohort Effects on Breast Cancer Incidence.

Breast cancer is the most commonly diagnosed cancer among women worldwide. Studies have reported minimal birth cohort effects on the incidence rates of breast cancer in Western countries but have reported notable birth cohort effects in some Asian countries. The risks of breast cancer may also vary within a country. In the present study, we abstracted female invasive breast cancer data from the Taiwan Cancer Registry for the period 1997-2016. We used the age-period-cohort model to compare birth cohort effects on breast cancer incidence rates between urban and rural regions in Taiwan. We identified a notable urban-rural disparity in birth cohort effects on breast cancer incidence rates in women in Taiwan. The incidence rates in the urban regions were higher than those in the rural regions across all cohorts. However, the incidence rates rose faster in the rural regions than in the urban regions across the cohorts. The risks of breast cancer observed for women born in 1992 were approximately 22 and 11 times than those observed for women born in 1917 in rural and urban regions, respectively. The observed gap in breast cancer incidence rates between the urban and rural regions gradually disappeared across the cohorts. Accordingly, we speculate that urbanization and westernization in Taiwan may be the drivers of female breast cancer incidence rates across birth cohorts.

Contrast-enhanced mammography (CEM) versus MRI for breast cancer staging detection of additional malignant lesions not seen on conventional imaging.

Contrast-enhanced mammography (CEM) is more available than MRI for breast cancer staging but may not be as sensitive in assessing disease extent. We compared CEM and MRI in this setting. Fifty-nine women with invasive breast cancer underwent preoperative CEM and MRI. Independent pairs of radiologists read CEM studies (after reviewing a 9-case set prior to study commencement) and MRI studies (with between 5 and 25 years of experience in breast imaging). Additional lesions were assigned National Breast Cancer Centre (NBCC) scores. Positive lesions (graded NBCC ≥ 3) likely to influence surgical management underwent ultrasound andor needle biopsy. True-positive lesions were positive on imaging and pathology (invasive or in situ). False-positive lesions were positive on imaging but negative on pathology (high-risk or benign) or follow-up. False-negative lesions were negative on imaging (NBCC < 3 or not identified) but positive on pathology. The 59 women had 68 biopsy-proven malignant lesions detected on mammographyultrasound, of which MRI demonstrated 66 (97%) and CEM 67 (99%) (p 1.000). Forty-one additional lesions were detected in 29 patients six of 41 (15%) on CEM only, 2341 (56%) on MRI only, 1241 (29%) on both CEM detected 16 and MRI 66 malignant additional lesions (p 0.063), with a positive predictive value (PPV) of 113 (8%) and 626 (23%) (p 0.276). While MRI and CEM were both highly sensitive for lesions detected at mammographyultrasound, CEM may not be as sensitive as MRI in detecting additional otherwise occult foci of malignancy. Australian and New Zealand Clinical Trials Registry ACTRN 12613000684729.

Magnetic Thermosensitive Liposomes Loaded with Doxorubicin.

Liposome-mediated anticancer drug delivery has the advantage of limiting the massive cytotoxicity of chemotherapeutic agents. Doxorubicin (DOX) PEG-liposomal does however have a slow-release rate that hinders its therapeutic efficacy. In this study, an integrated therapeutic system based on magnetic thermosensitive liposomes was designed. The chelated gadolinium acquired magnetic properties in the liposomes. The hyperthermia induced by ultra-high-field magnetic resonance imaging (UHF-MRI) enhances the chemotherapeutic effects of DOX. The DOX release from liposomes was facilitated over a narrow range of temperatures owing to the phase transition temperature of the liposomes. The magnetic properties of the liposomes were evident by the elevation of contrast after the exposure to UHF-MRI. Moreover, triple-negative breast cancer (TNBC) cells showed a significant decrease in cellular viability reaching less than 40% viability after 1 h of exposure to UHF-MRI. The liposomes demonstrated a physiological coagulation time and a minimal hemolytic potential in hemocompatibility studies therefore, they were considered safe for physiological application. As a result, magnetic-thermosensitive liposomal guidance of local delivery of DOX could increase the therapeutic index, thereby reducing the amount of the drug required for systemic administration and the chance of affecting the adjacent tissues.

Effects of trastuzumab and trastuzumab emtansine on corrected QT interval and left ventricular ejection fraction in patients with metastatic (HER2) breast cancer.

Trastuzumab and trastuzumab emtansine are specific antibody and antibody-drug conjugates used in the treatment of human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer. The aim of this study was to test their effect on the QTc interval duration and left ventricular ejection fraction (LVEF) in our patients, two parameters used in evaluation of cardiotoxicity. From May 2015 to October 2017, 26 patients with preserved LVEF were included in the study. All of them were previously treated with standard paclitaxel and cisplatin-based chemotherapy regimens. Electrocardiogram (ECG) was recorded just before each trastuzumab dose application and six months after the last dose. Echocardiography with LVEF measurement was performed several days before the application of the initial dose, and six months after the last cycle. Later, 24 patients with metastatic disease received additional treatment with trastuzumab emtansine after six months and the same ECG and echocardiography protocol was performed again. Due to reduction in LVEF, two patients were discontinued from additional treatment. A statistically significant QTc prolongation was found after each drug dose application, with an increase in mean QTc duration with every successive application, reaching the peak QTc values just before the fifth cycle of treatment. The QTc interval returned to its initial value six months after the last cycle (p < 0.001). These results were similar for both drugs. Mean LVEF before both treatment protocols was significantly higher compared to LVEF value after the treatment. LVEF before trastuzumab emtansine treatment was non-significantly higher than LVEF after trastuzumab treatment. Trastuzumab and trastuzumab emtansine cardiotoxicity manifested as a significant and progressive QTc prolongation after successive drug applications, reaching the peak value just before the fifth cycle of both drugs. Both medications also caused statistically significant but asymptomatic LVEF reduction. Complete reversibility of cardiotoxic effects of both drugs was confirmed by QTc interval and LVEF normalisation after the treatment discontinuation.

Receptive music therapy versus group music therapy with breast cancer patients hospitalized for surgery.

Hospitalization for breast surgery is a distressing experience for women. This study investigated the impact of music therapy (MT), an integrative approach that is characterized by the establishment of a therapeutic relationship between patients and a certified music therapist, through different musical interventions targeted to the specific needs of the patients. The impact of two different MT experiences was compared on anxiety and distressing emotions. One hundred fifty-one patients during hospitalization for breast surgery were randomly assigned to two music therapy treatment arms individualreceptive (MTri) vs. groupactive-receptive integrated (MTiGrp). Stress, depression, anger, and need for help were measured with the emotion thermometers (ET) and State Trait Anxiety Inventory Y-1 form (STAY-Y1). Data were collected before and after the MT intervention. Both types of MT interventions were effective in reducing all the variables stress, depression, anger, and anxiety (T Student p‹0.01). Patients perception of help received was correlated with a significant reduction in anxiety and distressing emotions during hospitalization for breast surgery. Considerations regarding the implementation of MT interventions in clinical practice are discussed. In individual receptive MT, there was a significant decrease in anxiety levels, whereas in the integrated MT group, there was a higher perception of help received and use of inter-individual resources.

Neighborhood and racial influences on triple negative breast cancer evidence from Northeast Ohio.

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) with higher recurrence rates and poorer prognoses and most prevalent among non-Hispanic Black women. Studies of multiple health conditions and care processes suggest that neighborhood socioeconomic position is a key driver of health disparities. We examined roles of patients neighborhood-level characteristics and race on prevalence, stage at diagnosis, and mortality among patients diagnosed with BC at a large safety-net healthcare system in Northeast Ohio. We used tumor registry to identify BC cases from 2007 to 2020 and electronic health records and American Community Survey for individual- and area-level factors. We performed multivariable regression analyses to estimate associations between neighborhood-level characteristics, measured by the Area Deprivation Index (ADI), race and comparative TNBC prevalence, stage at diagnosis, and total mortality. TNBC was more common among non-Hispanic Black (53.7%) vs. non-Hispanic white patients (46.4%). Race and ADI were individually significant predictors of TNBC prevalence, stage at diagnosis, and total mortality. Race remained significantly associated with TNBC subtype, adjusting for covariates. Accounting for TNBC status, a more disadvantaged neighborhood was significantly associated with a worse stage at diagnosis and higher death rates. Our findings suggest that both neighborhood socioeconomic position and race are strongly associated with TNBC vs. other BC subtypes. The burden of TNBC appears to be highest among Black women in the most socioeconomically disadvantaged neighborhoods. Our study suggests a complex interplay of social conditions and biological disease characteristics contributing to racial disparities in BC outcomes.

Comparison of goserelin and leuprorelin for ovarian protection during chemotherapy in young patients with breast cancer.

Although different gonadotropin-releasing hormone (GnRH) agonists may have different effects, their effect of ovarian protection during chemotherapy for breast cancer has not been compared. This study aimed to compare the effects of goserelin and leuprorelin for ovarian protection during chemotherapy in young patients with breast cancer. This prospective study analyzed 193 patients with breast cancer aged ≤ 40 years who had regular menstruation and serum anti-Müllerian hormone (AMH) levels ≥ 1 ngmL before treatment. Patients received either goserelin or leuprorelin for ovarian protection during doxorubicincyclophosphamide-based chemotherapy. Resumption of menstruation and changes in serum levels of AMH were compared between the two groups at 12 months after completion of chemotherapy. The mean age and the pretreatment serum AMH level were 33.2 years and 4.4 ngmL in goserelin group and 34.2 years and 4.0 ngmL in leuprorelin group. The proportion of patients who resumed menstruation was not different between the goserelin (94.4%) and leuprorelin (95.3%) groups at 12 months after chemotherapy completion. Serum AMH levels decreased significantly in both the goserelin (from 4.4 to 1.2 ngmL) and leuprorelin (from 4.0 to 1.2 ngmL) groups, with no statistical significance. In addition, no difference was found in the proportion of patients with serum AMH levels ≥ 1 ngmL between the goserelin (49.5%) and leuprorelin (44.2%) groups at 12 months after chemotherapy. Goserelin and leuprorelin were comparable in terms of ovarian protection during doxorubicincyclophosphamide-based chemotherapy in young patients with breast cancer.

Tumor selective Ru(III) Schiff bases complexes with strong in vitro activity toward cisplatin-resistant MDA-MB-231 breast cancer cells.

Novel ruthenium(III) complexes of general formula NaRuCl

Oncological surgery follow-up and quality of life meta-analysis.

Previous trials found that more intensive postoperative surveillance schedules did not improve survival. Oncological follow-up also provides an opportunity to address psychological issues (for example anxiety, depression, and fear of recurrence). This systematic review assessed the impact of a less intensive surveillance strategy on health-related quality of life (HRQoL), emotional well-being, and patient satisfaction. A systematic search was conducted in PubMedMEDLINE, Embase, Web of Science, Cochrane database, PsycINFO, and Google Scholar to identify studies comparing different follow-up strategies after oncological surgery and their effect on HRQoL and patient satisfaction, published before 4 May 2022. A meta-analysis was conducted on the most relevant European Organisation for Research and Treatment of Cancer QLQ-C30 and Hospital Anxiety and Depression Scale subscales. Thirty-five studies were identified, focusing on melanoma (4), colorectal (10), breast (7), prostate (4), upper gastrointestinal (4), gynaecological (3), lung (2), and head and neck (1) cancers. Twenty-two studies were considered to have a low risk of bias, of which 14 showed no significant difference in HRQoL between follow-up approaches. Five studies with a low risk of bias showed improved HRQoL or emotional well-being with a less intensive follow-up approach and three with an intensive approach. Meta-analysis of HRQoL outcomes revealed no negative effects for patients receiving less intensive follow-up. Low-intensity follow-up does not diminish HRQoL, emotional well-being, or patient satisfaction.

Pathological features and immune microenvironment in HER-2 intratumoral heterogeneous breast cancers.

Epidemiology and Risk Factors for Breast Cancer 21st Century Advances, Gaps to Address through Interdisciplinary Science.

Research methods to study risk factors and prevention of breast cancer have evolved rapidly. We focus on advances from epidemiologic studies reported over the past two decades addressing scientific discoveries, as well as their clinical and public health translation for breast cancer risk reduction. In addition to reviewing methodology advances such as widespread assessment of mammographic density and Mendelian randomization, we summarize the recent evidence with a focus on the timing of exposure and windows of susceptibility. We summarize the implications of the new evidence for application in risk stratification models and clinical translation to focus prevention-maximizing benefits and minimizing harm. We conclude our review identifying research gaps. These include pathways for the inverse association of vegetable intake and estrogen receptor (ER)-ve tumors, prepubertal and adolescent diet and risk, early life adiposity reducing lifelong risk, and gaps from changes in habits (e.g., vaping, binge drinking), and environmental exposures.

Human Ductal Carcinoma In Situ Advances and Future Perspectives.

Due to widespread adoption of screening mammography, there has been a significant increase in new diagnoses of ductal carcinoma in situ (DCIS). However, DCIS outcomes remain unclear. A large fraction of human DCIS (>50%) may not need the multimodality treatment options currently offered to all DCIS patients. More importantly, while we may be overtreating many, we cannot identify those most at risk of invasion or metastasis following a DCIS diagnosis. This review summarizes the studies that have furthered our understanding of DCIS pathology and mechanisms of invasive progression by using advanced technologies including spatial genomics, transcriptomics, and multiplex proteomics. This review also highlights a need for rethinking DCIS with a more focused view on epithelial states and programs and their cross talk with the microenvironment.

Newly Developed Targeted Therapies Against the Androgen Receptor in Triple-Negative Breast Cancer A Review.

Among different types of breast cancers (BC), triple-negative BC (TNBC) amounts to 15% to 20% of breast malignancies. Three principal characteristics of TNBC cells are (i) extreme aggressiveness, (ii) absence of hormones, and (iii) growth factor receptors. Due to the lack or poor expression of the estrogen receptor, human epidermal growth factor receptor 2, and progesterone receptor, TNBC is resistant to hormones and endocrine therapies. Consequently, chemotherapy is currently used as the primary approach against TNBC. Expression of androgen receptor (AR) in carcinoma cells has been observed in a subset of patients with TNBC therefore, inhibiting androgen signaling pathways holds promise for TNBC targeting. The new AR inhibitors have opened up new therapy possibilities for BC patients carrying AR-positive TNBC cells. Our group provides a comprehensive review of the structure and function of the AR and clinical evidence for targeting the cells nuclear receptor in TNBC. We updated AR agonists, inhibitors, and antagonists. We also presented a new era of genetic manipulating CRISPRCas9 and nanotechnology as state-of-the-art approaches against AR to promote the efficiency of targeted therapy in TNBC. SIGNIFICANCE STATEMENT The lack of effective treatment for triple-negative breast cancer is a health challenge. The main disadvantages of existing treatments are their side effects, due to their nonspecific targeting. Molecular targeting of cellular receptors, such as androgen receptors, increased expression in malignant tissues, significantly improving the survival rate of breast cancer patients.

Design, synthesis, and anti-triple negative breast cancer activity of novel Toosendanin derivatives.

Toosendanin (TSN) is a natural anti-cancer compound that is isolated from the traditional Chinese herbal Melia toosendan Sieb et Zucc. However, the research effect of TSN in the treatment of Triple negative breast cancer (TNBC) is still far from ideal. In this work, we investigated TSN and its derivatives in terms of their actions against MDA-MB-231 and HCC1806 TNBC cell lines. The results indicated that TSN and its derivative 11 showed excellent antitumor activity. Preliminary mechanistic studies showed that both compounds TSN and 11 induced S-phase arrest and G2M phase cell number decrease in HCC1806 cells. Also, TSN and 11 significantly reduced the protein level of the well-known cancer suppressor gene p53, reduced the phosphorylation of AKT and ERK, and also induced the accumulation of phosphorylated p38 and p21.

Tamoxifen retinopathy.

Tamoxifen (TAM) is a selective estrogen receptor modulator that is used in the treatment of breast cancer. As there are estrogen receptors in the retina, retinal pigment epithelium, and choroid, these tissues may also be affected by TAM. We describe the reported effects of TAM on the retina and choroid. Medical databases were searched using relevant keywords and the results were extracted and pooled. The incidence of retinalchoroidal toxicity ranged from 0.9% to 12%. There was a wide range for the time of exposure prior to the development of TAM retinopathy (3 weeks to 13 years). While functional measurements may be appropriate for assessment of TAM retinopathy, they have not been effective for screening patients. There is no generally accepted screening modality, but serial funduscopy and optical coherence tomography imaging seem to be the most reasonable approach for detecting early TAM-induced retinal toxicity.

Self-assembled nanocomposites of carboxymethyl β-dextranprotamine sulfate for enhanced chemotherapeutic drug sensitivity of triple-negative breast cancer by autophagy inhibition via a ternary collaborative strategy.

Drug resistance in cancer chemotherapy is a major confounding factor affecting the effectiveness of chemotherapeutic agents, thereby leading to poor clinical outcomes. Most chemotherapeutic drugs can induce protective autophagy and increase the resistance of tumors to chemotherapeutic drugs and reduce effective drug delivery to tumor cells. In this study, a tri-drug nanocomposite (NP) delivery system was devised using carboxymethyl β-dextran (CMD) and protamine sulfate (PS), two natural materials with good bio-compatibility. They were designed to carry the chemotherapeutic drug docetaxel (DTX), the autophagy inhibitor chloroquine (CQ), and Atg5 siRNA to cancer cells. The CQ DTX Atg5 siRNA NPs was driven by electrostatic interaction and self-assembly methods. The breast cancer cell line MDA-MB-231 was used for both cell culture and establishing mouse xenograft model. Our findings demonstrated that CQ and Atg5 siRNA encapsulated in NPs could enhance the sensitivity of tumor cells to DTX. The NPs exhibited remarkable considerable therapeutic effects for treating triple-negative breast cancer (TNBC) and good biosafety. Therefore, we established a novel multifunctional nanoplatform based on CMD and PS that enhances chemotherapeutic drug sensitivity through an autophagy inhibition strategy, providing new opportunities to overcome conventional drug resistance and enhance therapeutic efficiency against TNBC.

Associations of Physical Activity With Breast Cancer Risk Findings From the UK Biobank Prospective Cohort Study.

Although physical activity (PA) has been consistently associated with breast cancer, existing evidence is limited to self-reported physical activity, which is prone to dilution bias. Therefore, this aims to examine the associations of device-measured PA domains with breast cancer risk and whether it differs by menopausal status. Prospective cohort study. Data from 48,286 women from the UK Biobank cohort were analyzed. A wrist triaxial accelerometer was used to collect physical activity data for light, moderate, vigorous, moderate to vigorous, and total PA. Cox proportional models were performed to examine the association between PA domains, menopausal status, and breast cancer risk. Eight hundred thirty-six breast cancer cases were diagnosed during a median of 5.4 years (interquartile range 4.7-5.9). For total PA, those in the most active quartile had a 26% lower risk of breast cancer (Hazard ratio HR 0.74 95% confidence interval CI, 0.61-0.91) compared with those least active. Similar results were observed for light PA (HR 0.79 95% CI, 0.64-0.96), and moderate to vigorous PA (HR 0.78 95% CI, 0.64-0.96). However, moderate PA (HR 0.73 95% CI, 0.44-1.19) and vigorous PA (HR 0.77 95% CI, 0.56-1.05) was nonsignificant. No evidence of interaction between PA domains and menopause status was found (P > .10). High levels of PA are associated with a lower risk of breast cancer with similar magnitude of associations observed across different intensity domains.

Cost-effectiveness of sacituzumab govitecan versus chemotherapy in advanced or metastatic triple-negative breast cancer.

The ASCENT trial demonstrated the efficacy of sacituzumab govitecan for the treatment of advanced or metastatic triple-negative breast cancer (TNBC). The current study evaluated the cost-effectiveness of receiving sacituzumab govitecan compared with standard of care chemotherapy from the United States payer perspective. A partitioned survival approach was used to project the disease course of advanced or metastatic TNBC. Two survival modes were applied to analyze two groups of patients. The survival data were gathered from the ASCENT trial. Direct medical costs were derived from the data of Centers for Medicare Medicaid Services. Utility data was collected from the published literature. The incremental cost-utility ratio (ICUR) was the primary outcome that measured the cost-effectiveness of therapy regimen. One-way sensitivity and probabilistic sensitivity analysis were implemented to explore the uncertainty and validate the stability of results. In the base-case, the ICUR of sacituzumab govitecan versus chemotherapy is $ 778,771.9QALY and $ 702,281QALY for full population group and brain metastatic-negative (BMN) group with the setting of classic survival mode. And in the setting of cure survival mode, the ICUR is $ 506,504.5QALY for the full population group and $ 274,232.0QALY for BMN population group. One-way sensitivity analyses revealed that the unit cost of sacituzumab govitecan and body weight were key roles that lower the ICUR value. Probabilistic sensitivity analyses also showed that reducing the unit price of sacituzumab govitecan can improve the likelihood of becoming cost-effective. The cost-effectiveness analysis suggested that from a US payer perspective, sacituzumab govitecan at current price is unlikely to be a preferred option for patients with advanced or metastatic TNBC at a threshold of $ 150,000QALY.

Comprehensive landscape of the IPAF inflammasomes in pan-cancer A bulk omics research and single-cell sequencing validation.

IPAF (ICE-protease Activating Factor) is a nucleotide-bindingleucine-rich repeat (NLR) protein known as the cysteine-associated recruitment domain 12 (CARD12). Previous studies only discuss the role of IPAF inflammasomes in specific tumors. The role of IPAF inflammasomes in pan-cancer is still unclear. Therefore, we performed a comprehensive analysis of IPAF inflammasome in 33 tumors. We used databases like The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) from the UCSC XENA (httpxena.ucsc.edu) to retrieve and analyze gene expression. The influence of IPAF inflammasome on the prognosis of tumor patients was analyzed using univariate Cox regression analysis and Kaplan-Meier survival analysis. Furthermore, we conducted the following analysis Single-sample gene set enrichment analysis, single-cell level functional state analysis, single-cell sequencing, immune cell infiltration analysis, and tumor immune dysfunction and exclusion (TIDE) score. First, the differential expression of IPAF inflammasome-related genes (IPAF-RGs) in 33 tumors were analyzed. The results revealed that IPAF-RGs were significantly and differentially expressed in eight tumors. The prognostic significance of IPAF inflammasome scores was different in different tumors. A positive correlation was observed between IPAF inflammasomes scores and CD8 T cells in most tumors. Further analysis revealed that IPAF inflammasome might affect tumor immunity mainly by mediating effector T cell recruitment via the expression of chemokines such as CXCL9, CXCL10, and CCL5. The analysis of TIDE and IPAF inflammasome scores revealed a significant negative correlation between IPAF inflammasome and TIDE scores in 11 tumors. A pan-cancer analysis of IPAF inflammasome in various tumors was performed. The results highlight the potential value of IPAF inflammasome in response to immunotherapy in patients and provide a new direction for future immunotherapy.

G-CSF filgrastim biosimilar-Sandoz reduces the incidence of febrile neutropenia in patients receiving chemotherapy regimens with rest periods not exceeding 14 days A French, multicenter, prospective, non-interventional study.

The objective of this study was to describe filgrastim biosimilar-Sandoz modalities of use in patients receiving cytotoxic chemotherapy regimens with a rest period of ≤14 days and to investigate the incidence of febrile neutropenia (FN) in routine clinical practice. This was a French, multicenter, prospective and descriptive, non-interventional study including patients with breast, lung, gastrointestinal cancer or a lymphoma initiating filgrastim biosimilar-Sandoz treatment and in the context of cytotoxic chemotherapy with a rest period not exceeding 14 days. Data were collected during two routine clinical visits on the modalities of use of filgrastim biosimilar-Sandoz, on the incidence of neutropenia events and on adverse events. Between November 2015 and June 2018, 1080 patients were enrolled in the study in 129 centers. Overall, 941 patients were evaluable for efficacy and 937 for safety. Of the 941 patients, 84.8% had a solid tumor and 15.2% had a lymphoid hemopathy. Filgrastim biosimilar-Sandoz was prescribed as primary prophylaxis in 74.0% of the patients and as secondary prophylaxis in 22.4% of the patients. FN was reported in 1.5% of patients with a solid tumor and 12.6% of patients with a lymphoma. A chemotherapy relative dose intensity of over 85% with regard to the reference dose was achieved by more than 80% of the patients in all tumor localizations. The study showed that filgrastim biosimilar-Sandoz is safe to use and effective in preventing FN and in allowing to maintain the dose intensity of chemotherapy.

NAVIGATION SURGERY FOR INTRAOPERATIVE SENTINEL LYMPH NODE DETECTION USING ICG IN BREAST CANCER PATIENTS.

In 2020 more than 2.2 million cases of breast cancer were registered, and these figures indicate that this disease is very widespread. Lymphatic metastasis is one of the most important causes of local recurrence of breast cancer and is unfavorable factor of prognosis. The purpose of the work is to improve the method of intraoperative diagnosis of the sentinel lymph node in patients with breast cancer. Between 2016 and 2021, 200 patients with T1-T3N0M0 breast cancer were operated at the Odesa Regional Clinical Hospital. Two types of dyes - Patent Blue and ICG were used. The patients who had mastectomy with sentinel lymph node biopsy as a rule had a clinical diagnosis of T2-T3N0M0 breast cancer. In group 1, 100 patients had sentinel lymph node biopsy. Staining of lymph nodes was performed using Patent Blue. In group 2, 100 patients, sentinel lymph nodes biopsy was conducted using fluorescent dye ICG, which was also administered subdermally. A total five-year survival rate after axillary lymph dissection and sentinel lymph node biopsy was 91% and 92%, respectively. A five-year recurrence-free survival rate after axillary lymph dissection was approximately 82.2%, and after sentinel lymph node biopsy - 83.9%. Regional recurrence in the sentinel lymph nodes on the affected side were found in only 1.1% of cases. The sentinel lymph nodes were intact in 58% of patients, so, the next lymph dissection was not performed. The affected lymph nodes were observed in 42% of patients. The time of follow-up ranged from 60 to 180 months. The recurrence was registered in 0.2%. The study revealed no difference in total and recurrence-free survival rate between the groups. With detected mts lesions of the axillar (sentinel) lymph nodes, the operation should be continued with an obligatory determination of the second and third order lymph nodes. The extent of surgical intervention is determined on the operating table based on the results of intraoperative histological examination. The fluorescent lymphography method has a high accuracy - 99%, which allows to recommend it for implementation into clinical practice.

PATHOLOGIC FINDINGS IN GENDER-AFFIRMING MASTECTOMY A SYSTEMATIC REVIEW.

Following increased cultural awareness, expanded access to care, and decreased stigmatization, the number of transgender individuals seeking gender affirmation surgery such as gender-affirmation mastectomy (GAM) continues to rise. While post-mastectomy breast tissue is often sent for pathologic evaluation, few studies address the utility and standardization of this practice. This literature review evaluates the pathology findings in GAM specimens reported in the medical literature. A systematic review following PRISMA guidelines was performed to evaluate all medical publications related to pathology reports following GAM. The overall type and incidence of benign and malignant breast lesions were analyzed to elucidate which patient characteristics significantly affect the pathology findings. Overall, eight of 488 identified studies met inclusion criteria (1278 patients). The incidence of pre-malignant lesions was 2.42%, including flat epithelial atypia (0.08%), atypical hyperplasia (0.23%), atypical ductal hyperplasia (1.33%), atypical lobular hyperplasia (0.39%), and lobular carcinoma in situ (0.39%).Patient age, hormonal therapy, and family patient history of breast cancer were inconsistently reported among included studies. Lack of standardized pathologic classification did not permit further statistical analysis. Although patients who undergo GAM are unlikely to have premalignant or malignant findings on breast pathology examination, pathologic evaluation of breast tissue remains common practice. Additional studies, which include a standardized method of pathologic evaluation, are necessary before practice guidelines can be recommended.

US Food and Drug Administration Approval Summary Fam-Trastuzumab Deruxtecan-nxki for Human Epidermal Growth Factor Receptor 2-Low Unresectable or Metastatic Breast Cancer.

The US Food and Drug Administration approved fam-trastuzumab deruxtecan-nxki (DS-8201a, T-DXd) for the treatment of adult patients with unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-low (immunohistochemistry 1 or immunohistochemistry 2in situ hybridization-) breast cancer who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy. Approval was based on DESTINY-Breast04, a phase III, randomized, open-label, multicenter trial in patients with unresectable or metastatic HER2-low breast cancer, determined at a central laboratory. A total of 557 patients were randomly assigned (21) to receive either T-DXd 5.4 mgkg intravenously once every 3 weeks (n 373) or physicians choice of chemotherapy (n 184). The study met its primary efficacy end point of progression-free survival (PFS) by blinded independent central review assessment in the hormone receptor-positive (HR) cohort (N 494) with an estimated hazard ratio (HR) of 0.51(95% CI, 0.40 to 0.64 The approval of T-DXd in HER2-low metastatic breast cancer was based on statistically significant and clinically meaningful PFS and OS improvements observed in the DESTINY-Breast04 trial and represents the first approved therapy specifically for the treatment of HER2-low metastatic breast cancer.

An HLA-GSPAG9STAT3 axis promotes brain metastases.

Brain metastases (BM) are the most common brain neoplasm in adults. Current BM therapies still offer limited efficacy and reduced survival outcomes, emphasizing the need for a better understanding of the disease. Herein, we analyzed the transcriptional profile of brain metastasis initiating cells (BMICs) at two distinct stages of the brain metastatic cascade-the premetastatic or early stage when they first colonize the brain and the established macrometastatic stage. RNA sequencing was used to obtain the transcriptional profiles of premetastatic and macrometastatic (non-premetastatic) lung, breast, and melanoma BMICs. We identified that lung, breast, and melanoma premetastatic BMICs share a common transcriptomic signature that is distinct from their non-premetastatic counterparts. Importantly, we show that premetastatic BMICs exhibit increased expression of HLA-G, which we further demonstrate functions in an HLA-GSPAG9STAT3 axis to promote the establishment of brain metastatic lesions. Our findings suggest that unraveling the molecular landscape of premetastatic BMICs allows for the identification of clinically relevant targets that can possibly inform the development of preventive andor more efficacious BM therapies.

Research Progress on Bioactive Metal Complexes against ER-Positive Advanced Breast Cancer.

Breast cancer is the most prevalent cancer in women and represents a serious disease that is harmful to life and health. In 1977, with the approval of tamoxifen, endocrine therapy has become the main clinical treatment for ER-positive (ER) breast cancer. Although patients initially respond well to endocrine therapies, drug resistance often emerges and side effects can be challenging. To overcome drug resistance, the exploration for new drugs is a priority. Metal complexes have demonstrated significant antitumor activities, and platinum complexes are widely used in the clinic against various cancers, including breast cancer. In this Perspective, the first section describes the classification and mechanism of endocrine therapy drugs for ER breast cancer, and the second section summarizes research since 2000 into metal complexes with activity toward ER breast cancer. Finally, we discuss the opportunities, challenges, and future directions for metal complexes in the treatment of ER breast cancer.

Homologation of the Alkyl Side Chain of Antimitotic Phenyl 4-(2-Oxo-3-alkylimidazolidin-1-yl)benzenesulfonate Prodrugs Selectively Targeting CYP1A1-Expressing Breast Cancers Improves Their Stability in Rodent Liver Microsomes.

Phenyl 4-(2-oxo-3-alkylimidazolidin-1-yl)benzenesulfonates (PAIB-SOs) are a new family of antimitotic prodrugs bioactivated in breast cancer cells expressing CYP1A1. In this study, we report that the

GLUT-Targeting Phototherapeutic Nanoparticles for Synergistic Triple Combination Cancer Therapy.

The combination of multimodal therapies into one nanocarrier system is promising for its potential to enhance treatment performance by overcoming the efficacy problems encountered in conventional monomodal therapy. In this study, targeted and multimodal therapeutic hybrid nanocarriers are fabricated for breast cancer treatments. In this context, the synthesized gold nanorods (AuNRd), photothermal therapy (PTT) agent, are coated with doxorubicin (DOX) conjugated, targeted, and biocompatible tetrablock glycopeptide (P(DMAEMA-

Pathways of the Dissociative Electron Attachment Observed in 5- and 6-Azidomethyluracil Nucleosides Nitrogen (N

5-Azidomethyl-2-deoxyuridine (5-AmdU,

Piezocatalytic 2D WS2 Nanosheets for Ultrasound-Triggered and Mitochondria-Targeted Piezodynamic Cancer Therapy Synergized with Energy Metabolism-Targeted Chemotherapy.

Piezoelectric nanomaterials that can generate reactive oxygen species (ROS) by piezoelectric polarization under an external mechanical force have emerged as an effective platform for cancer therapy. In this study, piezoelectric, two-dimensional (2D) WS

Application of novel breast biospecimen cell type adjustment identifies shared DNA methylation alterations in breast tissue and milk with breast cancer risk factors.

DNA methylation patterning is cell-type-specific and altered DNA methylation is well established to occur early in breast carcinogenesis, affecting non-cancerous, histopathologically normal breast tissue. Previous work assessing risk factor-associated alterations to DNA methylation in breast tissue has been limited, with even less published research in breast milk, a non-invasively obtained biospecimen containing sloughed mammary epithelial cells that may identify early alterations indicative of cancer risk. Here, we present a novel library for the estimation of the cellular composition of breast tissue and milk and subsequent assessment of cell type-independent alterations to DNA methylation associated with established breast cancer risk factors in solid breast tissue (n 95) and breast milk (n 48) samples using genome-scale DNA methylation measures from the Illumina HumanMethylation450 array. We identified 772 hypermethylated CpGs (P < 0.01) associated with age consistent between breast tissue and breast milk samples. Age-associated hypermethylated CpG loci were significantly enriched for CpG island shore regions known to be important for regulating gene expression. Among the overlapping hypermethylated loci mapping to genes, a differentially methylated region was identified in the promoter region of SFRP2, a gene observed to undergo promoter hypermethylation in breast cancer. Our findings suggest the potential to identify epigenetic biomarkers of breast cancer risk in noninvasively obtained, tissue-specific breast milk specimens. This work demonstrates the potential of using breast milk as a non-invasive biomarker of breast cancer risk, improving our ability to detect early stage disease and lowering the overall disease burden.

Changes in breast cancer risk and risk factor profiles among U.S.-born and immigrant Asian American women residing in the San Francisco Bay Area.

Breast cancer incidence rates in women of Asian descent have been increasing in the United States (U.S.) and Asia. In a case-control study of Asian American women from the San Francisco Bay Area, we assessed associations with birthplace and migration-related characteristics and compared risk factors between Asian American and non-Hispanic White women by birthplace and birth cohort. Birthplace and migration-related characteristics were associated with breast cancer risk only among women in the younger birth cohort (1951-1984) that comprised 355 cases diagnosed at age ≤55 years and 276 sister and population controls. Breast cancer risk was marginally increased among foreign-born women (OR1.40, 95% CI0.97-2.03) and two-fold among foreign-born Chinese women (OR2.16, 95% CI1.21-3.88). Two-fold increased risks were associated with migration at age ≥40 years and longer U.S. residence (≥30 years or ≥75% of life). The education level was high among both cases and controls. Differences in the prevalence of risk factors by birthplace and birth cohort suggest temporal changes in reproductive and lifestyle-related factors. The prevalence in risk factors was similar between foreign-born and U.S.-born women in the younger birth cohort, and did not fully explain the observed associations with birthplace and other migration characteristics. In contrast to studies from earlier decades, younger foreign-born Asian American women had a higher risk of breast cancer than U.S.-born Asian American women. It is important and urgent to understand what factors drive the increasing burden of breast cancer in women of Asian descent and implement effective prevention programs.

An Adapted Cancer Screening Education Program for Native American Women With Intellectual and Developmental Disabilities and Their Caregivers Protocol for Feasibility and Acceptability Testing.

Women with intellectual and developmental disabilities (IDD) do not undergo breast and cervical cancer screening at the same rate as women without IDD. IDDs are diagnosed in childhood, are lifelong, and involve difficulties in adaptive behaviors and intellectual functioning. Native American women also experience disparities in breast and cervical cancer screenings. Despite known disparities, women with IDD are often not included in health promotion programs, and there is a need for evidence-based programming for those with intersectional identities, such as Native American women with IDD. This study aims to assess the feasibility and acceptability of My Health My Choice (MHMC), an adaptation of the Women Be Healthy 2 program. There are 2 parts to the study adaptation of the Women Be Healthy 2 program and feasibility and acceptability testing of MHMC. Individuals aged over 18 years who identify as Native American females with IDD and their caregivers (N30 women-caregiver dyads) are eligible for the study. Participants, who are affiliated with 2 partnering sites in Arizona (1 rural and 1 urban), complete pre- and postsurveys assessing knowledge, self-efficacy, and screening expectations before and immediately after completing the program. In addition, all participants complete brief satisfaction surveys after each of the 6 educational sessions. A subsample of Native American women with an IDD (n12), caregivers (n12), and community health educators (n2) who participate in the MHMC program will provide semistructured qualitative input regarding the content, delivery, and cultural relevance of the program. The adaptation of the culturally responsive MHMC program was completed in August 2021. In November 2021, the project team began recruitment for feasibility and acceptability studies. Feasibility will be examined using participation metrics, and acceptability will be measured using satisfaction measures. Pre- and postmeasures in cancer screening knowledge, self-efficacy, and screening expectations will examine improvements among participants. The results of feasibility and acceptability testing of MHMC will guide future implementation studies of the program. DERR1-10.219637801.

Open-source, fully-automated hybrid cardiac substructure segmentation development and optimisation.

Radiotherapy for thoracic and breast tumours is associated with a range of cardiotoxicities. Emerging evidence suggests cardiac substructure doses may be more predictive of specific outcomes, however, quantitative data necessary to develop clinical planning constraints is lacking. Retrospective analysis of patient data is required, which relies on accurate segmentation of cardiac substructures. In this study, a novel model was designed to deliver reliable, accurate, and anatomically consistent segmentation of 18 cardiac substructures on computed tomography (CT) scans. Thirty manually contoured CT scans were included. The proposed multi-stage method leverages deep learning (DL), multi-atlas mapping, and geometric modelling to automatically segment the whole heart, cardiac chambers, great vessels, heart valves, coronary arteries, and conduction nodes. Segmentation performance was evaluated using the Dice similarity coefficient (DSC), mean distance to agreement (MDA), Hausdorff distance (HD), and volume ratio. Performance was reliable, with no errors observed and acceptable variation in accuracy between cases, including in challenging cases with imaging artefacts and atypical patient anatomy. The median DSC range was 0.81-0.93 for whole heart and cardiac chambers, 0.43-0.76 for great vessels and conduction nodes, and 0.22-0.53 for heart valves. For all structures the median MDA was below 6 mm, median HD ranged 7.7-19.7 mm, and median volume ratio was close to one (0.95-1.49) for all structures except the left main coronary artery (2.07). The fully automatic algorithm takes between 9 and 23 min per case. The proposed fully-automatic method accurately delineates cardiac substructures on radiotherapy planning CT scans. Robust and anatomically consistent segmentations, particularly for smaller structures, represents a major advantage of the proposed segmentation approach. The open-source software will facilitate more precise evaluation of cardiac doses and risks from available clinical datasets.

Socioeconomic Factors and Adherence to Health Care Recommendations in Adolescent and Young Adult Cancer Survivors.