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Genistein-induced mitochondrial dysfunction and FOXO3aPUMA expression in non-small lung cancer cells.

Genistein is a multifunctional natural compound. In this study, we demonstrate the activity of genistein on non-small lung cancer A549 and 95D cells. A CCK8 assay was used to detect the cytotoxicity of genistein (0, 25, 50, 100, 150, 200 and 250 μM) on A549 and 95D cells for 48 h. AnnexinV-FITCPI and TUNEL assay were performed to examine the apoptotic cell death induced by genistein (0, 50, 100 and 150 μM, 48 h). Intracellular reactive oxygen species (ROS) generation and mitochondrial membrane potential were measured by flow cytometry. Mitochondrial activity in A549 and 95D cells, treated with 0, 50, 100 and 150 μM genistein for 48 h was detected by MitoTracker Orange staining. Western blot analysis was performed to evaluate the expression of the mitochondrial apoptosis-related proteins. Meanwhile, the expression level of FOXO3aPUMA signalling was measured by flow cytometry and Western blot assay. IC Our data may provide basic information for further development of genistein as a promising lead compound targeting NSCLC by inducing mitochondrial apoptosis.

Relationship between certain hematological parameters and risk of breast cancer.

Breast cancer is a common cancer, accounting for approximately 30% of all new cases of cancer diagnosed in women. It is also one of the main causes of cancer-related death in women. Clinically, breast cancer screening and early diagnosis rely mainly on mammography, ultrasound imaging, etc., but these tests are expensive and complex and are not suitable for early screening of breast cancer. This study found that low hemoglobin-to-red cell distribution width ratio and high monocyte-to-high-density lipoprotein ratio were associated with increased breast cancer risk. Because the determination of hemoglobin-to-red cell distribution width ratio and monocyte-to-high-density lipoprotein ratio is relatively simple, economic and convenient, regular detection of related markers can provide valuable information for early detection of breast cancer.

RANK pathway in cancer underlying resistance and therapeutic approaches.

Cancer remains one of the deadliest diseases despite advances in treatment. Metastatic cancers are the leading cause of death for advanced cancer patients. Those with advanced cancer with osteolytic-type bone metastases have a significantly lower quality of life. A novel treatment plan is needed now more than ever for breast cancer patients with bone metastases. There are shreds of evidence that cancer cells in the bloodstream interact with the bone microenvironment and that this interaction is a contributing component to breast cancer progression. Preventing any stage of this cycle can result in anti-metastasis effects. Since RANKL interacts with its receptor RANK and plays an important role in the vicious cycle, it has proven to be a successful therapeutic target in cancer treatment. As a result, we have presented a complete overview of the RANK pathway in cancer and discussed RANK signaling and tumor microenvironment, and potential therapeutic approaches in this review.

Aldehyde dehydrogenase 2 polymorphism is associated with chemotherapy-related cognitive impairment in patients with breast cancer who receive chemotherapy.

Chemotherapy-related cognitive impairment (CRCI) is a common but easily overlooked condition that markedly affects the quality of life (QOL) of patients with breast cancer. The rs671 is a common gene polymorphism of aldehyde dehydrogenase 2 (ALDH2) in Asia that is involved in aldehyde metabolism and may be closely related to CRCI. However, no study has yet summarised the association between ALDH2 and CRCI. This study enrolled one hundred and twenty-four patients diagnosed with breast cancer according to the pathology results, genotyped for ALDH2 single-nucleotide polymorphisms (SNP) to explore these. The mini-mental state exam (MMSE), verbal fluency test (VFT), and digit span test (DST) results were compared in these patients before and after chemotherapy (CT). We found that patients with ALDH2 gene genotypes of rs671GG, rs886205GG, rs4648328CC, and rs4767944TT polymorphisms were more likely to suffer from cognitive impairment during chemotherapy. A trend toward statistical significance was observed for rs671GG of DST (z 2.769, p 0.006), VFT (t 4.624, P<0.001) rs886205GG of DST (z 3.663, P<0.001) rs4648328CC of DST (z 2.850, p 0.004), VFT (t 3.477, p 0.001) and rs4767944TT of DST (z 2.967, p 0.003), VFT (t 2.776, p 0.008). The cognitive indicators of these patients significantly decreased after chemotherapy (p < 0.05). The difference in ALDH2 rs671 was most obvious. Our results showed what kinds of ALDH2 genotyped patients that are more likely to develop CRCI. In the future, it may be possible to infer the risk of CRCI by detecting the single-nucleotide locus of ALDH2 that is conducive to strengthening clinical interventions for these patients and improving their QOL. More importantly, this study has important implications for Asian women with breast cancer as ALDH2 rs671 is a common polymorphism in Asians.

The role of DDX46 in breast cancer proliferation and invasiveness A potential therapeutic target.

DDX46, a member of DEAD-box (DDX) proteins, is associated with various cancers, while its involvement in the pathogenesis of breast cancer hasnt been reported so far. The study demonstrated the overexpression of DDX46 in human breast cancer cells and tissue samples, and correlated with high histological grade and lymph node metastasis. Downregulation of DDX46 in the breast cancer cell lines inhibited their proliferation and invasiveness in vitro. Furthermore, the growth of MDA-MB-231 xenografts was suppressed in nude mice by DDX46 knockingdown. Taken together, our findings suggest that DDX46 is an oncogenic factor in human breast cancer, and a potential therapeutic target.

mTOR complex activity and metabolic changes as potential targets in solid tumors.

We investigated the activity and inhibition of mTOR and other metabolic pathways with their clinical significance in human breast tumors (using ten cell lines and nearly a hundred biopsy samples).Based on our results, the metabolic and mTOR inhibitor treatments showed a moderate tumor growth inhibitory effect in the cell lines subtype independently, which indicates tumor cell and tissue adaptation. Providing human tissue samples, we found a subtype independent correlation between high mTOR activity and protein expression characterizing alternative metabolic pathways with increased expression and the poor prognosis of breast tumors. Breast tumors are characterized by metabolic heterogeneity and significant metabolic plasticity, which can be targeted by combining anti-metabolic treatments and new therapies. Concerning these, an immunohistochemical evaluation (IHC panel) can be recommended, which is suitable for both metabolic plasticity evaluation and recognition of cases that may require stricter follow-up or metabolic targeted therapy due to the expected poor prognosis.

Participation indicators of organized mammography screening in Hungary between 2012-2021.

The aim of our study is to analyze the participation indicators of screening rounds Nr. 6-10 (2012-2021) of the organized nationwide mammography screening program. Data derived from the nationwide financing database of the Hungarian National Health Insurance Fund Management and covered the period 2012-2021. We analyzed both diagnostic and screening mammography examinations. Between 2012 and 2019 the coverage (screening and diagnostic mammography) varied between 48.1-51.5, which decreased to 31.8% in 2020-2021. Within total coverage, the organized screening rate declined from 30.3-31.2 to 20.0, while the diagnostic mammography rate decreased from 17.7-20.7% to 11.8%. We can conclude that the number of both the diagnostic and screening mammography declined. In order to reduce the mortality of breast cancer, participation rate of mammography screening program should be increased.

The Hungarian situation of cancer epidemiology in the second decade of the 21st century.

Evaluation of cancer incidence and mortality is essential for the design and development of oncology networks. In Hungary the population-based epidemiological data collection in oncology is executed by the Hungarian National Cancer Registry, whilst, mortality statistics are compiled by the Hungarian Central Statistical Office. In this review, Hungarian cancer epidemiology of 2010s was presented, using population- based morbidity and mortality data, and positioning the country in European cancer statistics. According to GLOBOCAN estimations, Hungary suffers from the highest cancer incidence and mortality rates in Europe. We have reported a steady increase in the number of new cases, while mortality stagnated. Lung and colorectal cancers showed the highest incidence, which was followed by breast cancer. These three malignancies are responsible for almost half of the cancer-related deaths. Improving the quality of population- based disease registries, such as the Hungarian Cancer Registry, requires wide and extensive multidisciplinary collaborative work from many stakeholders.

Evaluation of the effects of newly synthesized metallophthalocyanines on breast cancer cell lines with photodynamic therapy.

In this study, the new phthalonitrile derivative 3-(4-(3-oxobutyl)phenoxy)phthalonitrile (1) and its non-peripheral metallophthalocyanine derivatives zinc (2), copper (3), cobalt (4), manganese (5), gallium (6), and indium (7) were synthesized. The newly synthesized phthalocyanines were characterized by standard spectroscopic methods, such as FT-IR,

Efficacy of minodronic acid for the prevention of osteoporosis in premenopausal women with gynaecologic disease who undergo bilateral oophorectomy a single-centre, non-randomised controlled, experimental study.

We evaluated the efficacy of minodronic acid for osteoporosis prevention after bilateral oophorectomy for gynaecologic disease in premenopausal women. Bone mineral density (BMD) and young adult mean (YAM) data from the lumbar vertebrae and femur and bone alkaline phosphatase (BAP)tartrate-resistant acid phosphatase 5 b (TRACP 5 b) data were obtained for 101 patients. The primary endpoint was the efficacy of minodronic acid for osteoporosis prevention. Fifty-five and 31 patients were assigned to medication and no medication groups, respectively. The decrease in BMD and YAM and the increase in BAPTRACP-5b were significantly more suppressed in the medication group. There were no significant between-group differences in age at oophorectomy, cancer type, body mass index (BMI), and adjuvant therapy. There were no adverse events due to minodronic acid. Minodronic acid may prevent osteoporosis after oophorectomy in premenopausal women with gynaecologic disease, independent of age at oophorectomy, cancer type, BMI, or adjuvant therapy. Impact statement

Prediction of Breast Cancer Through Random Forest.

During the life of a woman, 8% of women are diagnosed with Breast cancer. (BC) BC is the second most common cause of death in both developed and undeveloped countries. BC is characterized by the mutation of genes, constant pain, changes in the size, color(redness), and skin texture of breasts. Classification of breast cancer leads pathologists to find a systematic and objective prognostic, generally the most frequent classification is binary (benignmalignant). Machine Learning (ML) techniques are being broadly used in the breast cancer classification problem. They provide high classification accuracy and effective diagnostic capabilities. Breast cancer remains one of the top diseases that lead to thousands of death in women every year. Artificial intelligence (AI) has been utilized for early diagnosis, and rapid, and accurately identifying breast tumors. The objective of this paper is to research, determine and classify these tumors. Machine learning algorithm such as Random Forest (RF) is used to classify medical images into malignant and benign. Moreover, Machine learning has been employed recently for the same purpose. The results showed that Random Forest achieved high accuracy, therefore, the researchers utilized various functions for this algorithm and added more features such as bagging and boosting to increase its efficacy. Conclusion The random Forest algorithm, therefore, achieved an enhanced accuracy of 98%.

A Number of the N-terminal RASSF Family RASSF7.

The Ras association domain family 7 (RASSF7, also named HRC1), a potential tumor-related gene, located on human chromosome 11p15, has been identified as an important member of the N-terminal RASSF family. Whereas, the molecular biological mechanisms of RASSF7 in tumorigenesis remain to be further established. We perform a systematic review of the literature and assessment from PUBMED and MEDLINE databases in this article. RASSF7 plays a significant role in mitosis, microtubule growth, apoptosis, proliferation and differentiation. Many research literature shows that the RASSF7 could promote the occurrence and advance of human tumors by regulating Aurora B, MKK4, MKK7, JNK, YAP, MEK, and ERK, whereas, it might inhibit c-Myc and thus lead to the suppression of tumorigenesis. The pregulation of RASSF7 often occurs in various malignancies such as lung cancer, neuroblastoma, thyroid neoplasm, hepatocellular cancer, breast cancer and gastric cancer. The expression stage of RASSF7 is positively correlated with the tumor TNM stage. In this review, we primarily elaborate on the acknowledged structure and progress in the various biomechanisms and research advances of RASSF7, especially the potential relevant signaling pathways. We hope that RASSF7 , a prospective therapeutic target for human malignancies, could play an available role in future anti-cancer treatment.

A bright horizon of intelligent targeted-cancer therapy nanoparticles against breast cancer stem cells.

Breast cancer stem cells (BCSCs) are heterogeneous tumor-initiating cell subgroups of breast cancers that possess some stem cell markers and are sustained after chemotherapy. Due to BCSCs being sufficient for tumor relapse, and given that the biological behaviors of BCSCs are so complex, it is critical to figure out exactly how they work, learn more about their cell biology, and discover biomarkers and strategies for explicitly targeting and destructing cancer stem cells. In order to accomplish innovative treatment for breast cancer, it is also essential to target BCSCs. Despite the vast quantities of BCSC target chemicals, their therapeutic implementation is limited due to off-target behavior and bioavailability issues. Targeted drug delivery systems based on nanoparticles have advantages for transporting anti-BCSC materials, especially to targeted locations. Hence, breast cancer therapy using a nanoparticle-based BCSCs targeting system is a promising strategy. Such targeted drug delivery systems can resolve the biodistribution obstacles of nanosystems. Throughout this paper, we highlight various strategies for targeting BCSCs utilizing nano-based systems. In conclusion, issues about the inadequate stability of nanoparticles and the possibility for loaded drug leakage during delivery systems have yet to be answered. More fundamental and applied research is required, and proper methods such as coating or surface modification.

Design, Synthesis and Anti-cancer Activity Evaluation of a 3-methyleneisoindolin-1-one Library.

Isoindolin-1-ones are medicinally privileged heterocyclic compounds. Due to the interesting biological activities exhibited by these compounds, several synthetic and medicinal research groups have developed numerous synthetic approaches for these compounds. We have also previously reported two efficient approaches for the synthesis of the isoindolin-1-ones through iodoaminocyclization of alkynyl amides using n-BuLi and phosphazene superbases. To construct a medium size library of multisubstituted 3-methyleneisoindolin-1-ones, and to study its biological profile, specifically anti-cancer activity. Solution phase parallel synthesis has been performed for the synthesis of 3-methyleneisoindolin-1-ones library through n-BuLi-mediated iodoaminocyclization of 2‑(1-Alkynyl)benzamides. The iodocyclized products were further derivatized through palladium-catalyzed Sonogashira and Suzuki Miyaura couplings and N-alkylation reactions. In silico evaluation of the physicochemical and ADMET properties was performed to check the drug likeness of the library compounds. Selected isoindolin-1-one analogues were evaluated for in vitro antiproliferative activity in various human cancer cell lines (MCF-7, A-549, and U-373 MG). A library of 46 multisubstituted 3-methyleneisoindolin-1-ones has been synthesized. The iodo-isoindolin-1-ones were synthesized in 66-76% yields through n-BuLi-mediated iodoaminocyclization of 2‑(1-Alkynyl)benzamides. Further diversification afforded the diverse library members in Yields 40-96%. Two of the library compounds exhibited GI50 values of < 10 M in human breast cancer cell line (MCF-7). Isoindolin-1-one library was constructed through electrophilic cyclization. The diversification was successfully performed through various C-C and C-N bond formation reactions. The anti-proliferative activity of the library members appears to be arising from the interaction of the compounds with the protein kinase drug targets.

Upregulation of circ0008812 and circ0001583 predicts poor prognosis and promotes breast cancer proliferation.

Emerging roles of TRIM27 in cancer and other human diseases.

As a member of the TRIM protein family, TRIM27 is a RING-mediated E3 ubiquitin ligase that can mark other proteins for degradation. Its ubiquitination targets include PTEN, IκBα and p53, which allows it to regulate many signaling pathways to exert its functions under both physiological and pathological conditions, such as cell proliferation, differentiation and apoptosis. During the past decades, TRIM27 was reported to be involved in many diseases, including cancer, lupus nephritis, ischemia-reperfusion injury and Parkinsons disease. Although the research interest in TRIM27 is increasing, there are few reviews about the diverse roles of this protein. Here, we systematically review the roles of TRIM27 in cancer and other human diseases. Firstly, we introduce the biological functions of TRIM27. Next, we focus on the roles of TRIM27 in cancer, including ovarian cancer, breast cancer and lung cancer. At the same time, we also describe the roles of TRIM27 in other human diseases, such as lupus nephritis, ischemia-reperfusion injury and Parkinsons disease. Finally, we discuss the future directions of TRIM27 research, especially its potential roles in tumor immunity.

Developing a real-world database for oncology a descriptive analysis of breast cancer in Argentina.

Registries based on Real-World Data (RWD) are those obtained outside of systematised and randomised clinical trials. They allow the collection of information from a large number of patients and enable the participation of a significant number of professionals. PrecisaXperta is a web platform developed for this purpose with more than 2 years of operation, parameterised for oncology. Its design allows the construction of an epidemiological database in real time and exportable for processing. To describe the characteristics and operation of this online data recording tool, explain how it was developed and analyse the quality of the information recorded, taking as an example the data obtained for breast cancer. Physicians, computer scientists and data science analysts participated in the development. Patient data, history, educational level, diagnosis, staging, molecular markers, quality of life, types of treatments, progression and response, imaging, complications, adverse events are some of the fields included. Data treatment in terms of encryption, anonymisation, protection and validation is also explained. The selected breast cancer data for description were processed with medium-level statistical programmes, since the number required to apply Big Data engines is not yet available. From a total of 6,892 solid tumours, 1,892 were breast cancer and 1,654 were selected that complied with a data set minimum elaborated ad hoc. Cases from 13 provinces showed a geolocation bias according to the place of practice of the professionals in the collaborative network. The predominant lack of data was detected in molecular markers (ki67) and correlativity in some lines of treatment. Inconsistencies in dates and therapeutic schemes were also detected. Data curation made it possible to exclude them. The age of the patients was 55.3 ± 11.88 years. At the time of diagnosis, the predominance was in stage I 36.48% and II 30.06%, with positive hormone receptors in 1,424 (89.96%) cases. The predominant treatments were hormonal (61.54%) and target directed with 30.85% for HER2() and 39.14% for HER2(-) accompanied in most cases (85.9%) by some period of chemotherapy. Immunotherapy was much less represented (0.36%). Data were processed, homogenised, pooled and presented and made accessible in a form suitable for application to RWD analyses. PrecisaXperta fulfils this purpose of systematising the information to facilitate its loading with its simple and intuitive interface. From the analysis of the data obtained in breast cancer, it is clear that some fields should be mandatory in order to improve the quality of the information. The results describing the registered breast cancers give us a surface view of the affected population and prepare us to design future studies when we have local Big Data. This type of development, with continuous improvements and online results, will allow with its dissemination, that the participating professionals have information of what happens in the real world, having available in a democratic way, the epidemiology to be able to study, publish and investigate with these data.

CDK 46 inhibitors for adjuvant therapy in early breast cancer-Do we have a clear winner

CDK46 inhibitors have become the mainstay of treatment for patients with advanced hormone receptor positive and Human Epidermal Receptor -2 HER-2 negative breast cancer. Three CDK 46 inhibitor drugs are currently approved and available, including Palbociclib, Ribociclib and Abemaciclib. All three of these drugs have similar mechanism of action and other pharmacokinetic and pharmaco-dynamic properties and hold equivalent positions in cancer care guidelines. Surprisingly, however, in the adjuvant setting of early breast cancer, two trials of palbociclib have failed to show any benefit while abemaciclib has shown some early benefits in disease-free survival and has received approval for its use in adjuvant setting. In this article, we explore several reasons for this discrepancy in the results of CDK46 inhibitors in the adjuvant setting. We also question if we should already adopt adjuvant abemaciclib in our clinical practice given the uncertainty in data.

Highlights of the I Congress ecancer Choosing Wisely March 30 and 31, 2022 Santa Cruz, Bolivia.

The ecancer Choosing Wisely conference was held for the first time in Latin America in Santa Cruz, Bolivia. The event had more than 150 registered attendees in addition to 22 speakers from different countries and different specialities in the field of oncology, who presented topics on prevention, oncological surgery, clinical oncology and palliative care, in order to demonstrate the current evidence of how to approach a patient in daily clinical practice based on the human resources, materials and drugs available, trying to offer the maximum benefit to the patient based on current scientific evidence. In addition to addressing issues of vital importance in breast cancer, during the 2 days of the event, updated information generated in recent years was presented, the results of which will change clinical practice. All the experts were in favour of developing strategies and methods that help us to properly select treatments to optimise resources and reduce the economic toxicity of the most modern and current treatments. This conference was an event of vital importance because it was the first face-to-face event for ecancer and the physicians after difficult years due to COVID-19.

Spectrum and management of breast cancer patients with variant of uncertain significance mutations at a tertiary care centre in North India.

The spectrum and significance of Variants of Uncertain Significance (VUS) mutations in breast cancer predisposition genes is poorly defined in the Indian population. All new female breast cancer patients from 1 March 2019 to 28 February 2020 were screened. Those providing informed consent and without previous genetic testing were recruited. Multigene panel testing (107 genes) by next-generation sequencing was performed for all patients. Descriptive statistics was used to describe the spectrum of VUS mutations. Out of 236 patients recruited in the study, a VUS was detected in 89 patients (37.71%). VUS pathogenic ratio was 2.02. A total of 121 different VUS mutations in 40 different genes were detected. Fourteen patients (15.7%) had a VUS in high penetrance genes and 36 VUS mutations (29.8%) were detected in one of the genes involved in homologous recombination repair pathway. No therapeutic interventions were done based on VUS. In this large prospective study of genetic determinants of breast cancer from India, a high prevalence of VUS (37.71%) was detected with 15.7% patients having a VUS in high penetrance genes. More evidence needs to be generated from larger multicentric studies to better understand the implications of these genetic variants and enable their reclassification.

A revolution in cervical cancer prevention in Ghana.

Though cervical cancer is largely preventable, success depends on sustained screening and treatment of precancer. This is not available in many low resource settings where screening and treatment services are not available due to a lack of government support. Our vision of setting up a comprehensive cervical cancer prevention scheme across Ghana that offers services tailored to fit every patients needs, and relies on task shifting has been made possible through the setting up of the Cervical Cancer Prevention and Training Centre (CCPTC) to train and equip middle cadre staff (mostly nurses and midwives) to provide crucial cervical precancer screening and treatment services in many areas of the country that have never seen any such screening activities. To achieve this vision, we have learnt to produce crucial context relevant teaching materials and consumables locally, while adapting simple, readily available social media applications to raise crowd funds to support our work, use these apps to support routine work and to create a network of service providers at various service levels that can rely on each other and assure quality. Our vision has been supported by individuals and organizations that believe in it. They have allowed us to determine our growth and success. By sharing the experiences of the CCPTC we hope to encourage others to set up screening centers in low resource settings.

Breast Cancer in Geriatric Patients Current Landscape and Future Prospects.

Breast cancer is the most common cancer diagnosed among women worldwide and more than half are diagnosed above the age of 60 years. Life expectancy is increasing and the number of breast cancer cases diagnosed among older women are expected to increase. Undertreatment, mostly due to unjustifiable fears of advanced-age and associated comorbidities, is commonly practiced in this group of patients who are under-represented in clinical trials and their management is not properly addressed in clinical practice guidelines. With modern surgery and anesthesia, breast surgeries are considered safe and is usually associated with very low complication rates, regardless of extent of surgery. However, oncoplastic surgery and management of the axilla can be tailored based on patients- and disease-related factors. Most of chemotherapeutic agents, along with targeted therapy and anti-Human epidermal growth factor receptor-2 (HER2) drugs can be safely given for older patients, however, dose adjustment and close monitoring of potential adverse events might be needed. The recently introduced cyclin-D kinase (CDK) 46-inhibitors in combination with aromatase inhibitors (AI) or fulvestrant, which changed the landscape of breast cancer therapy, are both safe and effective in older patients and had substituted more aggressive and potentially toxic interventions. Despite its proven efficacy, adjusting or even omitting adjuvant radiation therapy, at least in low-risk older patients, is safe and frequently practiced. In this paper, we review existing data related to breast cancer management among older patients across the continuum from resection of the primary tumor through adjuvant chemotherapy, radiation and endocrine therapy up to the management of recurrent and advanced-stage disease.

The abscopal effect systematic review in patients with brain and spine metastases.

The abscopal effect is a rare phenomenon whereby local radiation induces a proposed immune-mediated anti-tumor effect at distant sites. Given the growing use of immunotherapies and systemic immune checkpoint inhibitors in neuro-oncologic practice, we aimed to review prior studies pertaining to this phenomenon in the context of tumor shrinkage both within the central nervous system as well as distant disease sites. A systematic review in accordance with the PRISMA guidelines was conducted to identify all studies which assessed the abscopal effect in patients with treated metastatic cancer to the brain andor spine. Articles were included if they reported the abscopal effect in patients (case studies) or if the abscopal effect was explicitly analyzed in case series with cohorts of patients with metastatic brain or spine tumors. Laboratory investigations and clinical trials investigating new therapies were excluded. Twenty reports met inclusion criteria 16 case reports, 4 case series ( Abscopal effects can occur following radiotherapy in patients with brain or spine metastases and is thought to be a result of increased anti-tumor immunity. The potential for immune checkpoint inhibitor therapy to be used in combination with radiotherapy to induce an abscopal effect is an area of active investigation.

Sarcopenia does not limit overall survival after interstitial brachytherapy for breast cancer liver metastases.

Sarcopenia has been identified as a prognostic marker of clinical outcomes in several diseases. However, the influence of sarcopenia on non-surgical local treatments in breast cancer liver metastases (BCLM) is unknown. Therefore, the purpose of this study was to assess the effect of sarcopenia among patients with BCLM undergoing interstitial brachytherapy (iBT). Aim of the study was to evaluate the influence of baseline computed tomography (CT) psoas body composition parameters, including psoas muscle area (PMA), psoas muscle index (PMI), muscle density, and skeletal muscle gauge (SMG) on clinical variables in patients undergoing image-guided iBT. Computed tomography scans of patients undergoing iBT for BCLM from 2006-2017 were retrospectively analyzed. PMA, PMI, and SMG were measured on pre-treatment CT scans. Parameters were associated with overall survival using logistic regression analysis. Sixty patients were included in the analysis. 27 patients (45%) were considered sarcopenic. Median overall survival was 27 months (SD 4.0 months). In univariate analysis, neither PMA (HR 0.956, 95% CI 0.855-1.068, Sarcopenia does not predict overall survival in patients undergoing iBT for BCLM. Interstitial BT may therefore be a suggested treatment option in sarcopenic patients with BCLM eligible for local ablation.

Escitalopram co-prescription in anastrozole-treated breast cancer patients.

The purpose of the study was to evaluate the impact of escitalopram co-prescription on plasma anastrozole levels in post-menopausal breast cancer patients. A total of 24 post-menopausal operated breast cancer patients co-prescribed with escitalopram and anastrozole were included. Blood samples were collected, before and 1-month after the onset of escitalopram to analyze plasma anastrozole and estradiol levels. No significant difference was noted in basal plasma anastrozole levels with respect to age, body mass index (BMI), tumor stage, previous antineoplastic treatments, concomitant medications, and serum estradiol levels. Overall, 17 patients completed the 1-month escitalopram treatment, while 7 patients discontinued escitalopram within the 1 Escitalopram co-prescription resulted in significant increase in plasma anastrozole levels without affecting the serum estradiol levels. Our findings emphasize the need for close monitoring in case of concomitant use of anastrozole and escitalopram, especially in obese patients and the potential role of therapeutic drug monitoring.

Differentiating Primary Tumors for Brain Metastasis with Integrated Radiomics from Multiple Imaging Modalities.

To differentiate the primary site of brain metastases (BMs) is of high clinical value for the successful management of patients with BM. The purpose of this study is to investigate a combined radiomics model with computer tomography (CT) and magnetic resonance imaging (MRI) images in differentiating BMs originated from lung and breast cancer. Pretreatment cerebral contrast enhanced CT and T1-weighted MRI images of 78 patients with 179 BMs from primary lung and breast cancer were retrospectively analyzed. Radiomic features were extracted from contoured BM lesions and selected using the Mann-Whitney A total of 10 and 6 optimal radiomic features were screened out of 1288 CT and 1197 MRI features, respectively. The mean area under the curves (AUCs) of the BLR and SVM models using fivefolds cross-validation were 0.703 vs. 0.751, 0.718 vs. 0.754, and 0.781 vs. 0.803 in the training dataset and 0.708 vs. 0.763, 0.715 vs. 0.717, and 0.771 vs. 0.805 in the testing dataset for models with CT alone, MRI alone, and combined CT and MRI radiomic features, respectively. Radiomics model based on combined CT and MRI features is feasible and accurate in the differentiation of the primary site of BMs from lung and breast cancer.

MCT4Lactate Promotes PD-L1 Glycosylation in Triple-Negative Breast Cancer Cells.

Triple-negative breast cancer (TNBC) has the highest percentage of lymphocytic infiltration among breast cancer subtypes, and TNBC patients may benefit from anti-PD-1PD-L1 immunotherapy. However, some cases whether the immune checkpoint blockade (ICB) shows low targeting efficiency have occurred and effective synergistic targets need to be found, which inspired our exploration of the co-expression analysis of MCT4 (SLC16A3) and PD-L1 (CD274) and their potential regulatory mechanisms. After bioinformatic analysis of the relationship between MCT4 and PD-L1, we validated their positive co-expression relationship in triple-negative breast cancer through multiple immunohistochemical staining (mIHC), CRISPRCas9, and lentiviral transduction for MCT4 knockout (sgMCT4231 KO) or overexpression (pEGFP-N1-MCT4231). We examined the effect of lactate treatment on PD-L1 expression in triple-negative breast cancer cells by qRT-PCR and Western blot. Combined with our results, we found that MCT4 positively regulated PD-L1 expression through discharging lactate and stabilized PD-L1 through promoting its glycosylation by the classic WNT pathway in MDA-MB-231 cells. More importantly, the high co-expression of MCT4 and PD-L1 appears to predict more effective targets for treating TNBC, which would improve immune checkpoint therapy for TNBC.

Identification of Six N7-Methylguanosine-Related miRNA Signatures to Predict the Overall Survival and Immune Landscape of Triple-Negative Breast Cancer through In Silico Analysis.

Triple-negative breast cancer (TNBC) is a widely prevalent breast cancer, with a mortality rate of up to 25%. TNBC has a lower survival rate, and the significance of N7-methylguanosine (m7G) modification in TNBC remains unclear. Thus, this study is aimed at investigating m7G-related miRNAs in TNBC patients through in silico analysis. In our research, RNA sequencing and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. The miRNAs targeting typical m7G modification regulators Methyltransferase-like 1 (METTL1) and WD repeat domain 4 (WDR4) were predicted on the TargetScan website. A miRNA risk model was built, and its prognostic value was evaluated by R soft packages. Single-sample gene set enrichment analysis was used to assess immune infiltration, and further expression of immune checkpoints was investigated. As a result, miR-421, miR-5001-3p, miR-4326, miR-1915-3p, miR-3177-5p, and miR-4505 were identified to create the risk model. A nomogram consisting of the stage N and risk model predicted overall survival effectively among TNBC patients. Treg and TIL were shown to be strongly linked to the risk model, and the high-risk group had higher levels of four immune checkpoints expression (CD28, CTLA-4, ICOS, and TNFRSF9). A risk model consisting of m7G-related miRNAs was constructed. The findings of the current study could be used as a prognostic biomarker and can provide a novel immunotherapy insight for TNBC patients.

A Tutorial on Generative Adversarial Networks with Application to Classification of Imbalanced Data.

A challenge unique to classification model development is imbalanced data. In a binary classification problem, class imbalance occurs when one class, the minority group, contains significantly fewer samples than the other class, the majority group. In imbalanced data, the minority class is often the class of interest (e.g., patients with disease). However, when training a classifier on imbalanced data, the model will exhibit bias towards the majority class and, in extreme cases, may ignore the minority class completely. A common strategy for addressing class imbalance is data augmentation. However, traditional data augmentation methods are associated with overfitting, where the model is fit to the noise in the data. In this tutorial we introduce an advanced method for data augmentation Generative Adversarial Networks (GANs). The advantages of GANs over traditional data augmentation methods are illustrated using the Breast Cancer Wisconsin study. To promote the adoption of GANs for data augmentation, we present an end-to-end pipeline that encompasses the complete life cycle of a machine learning project along with alternatives and good practices both in the paper and in a separate video. Our code, data, full results and video tutorial are publicly available in the papers github repository.

Studying the Anticancer Effects of Thymoquinone on Breast Cancer Cells through Natural Killer Cell Activity.

Cancer immunotherapy is quickly growing and can now be viewed as the fifth column of cancer treatment. In addition, cancer immunotherapy has shown promising results with different kinds of cancers and may be used as a complementary therapy with various types of treatments. Thus, immuno-oncology is showing astounding advantages. However, one of the main challenges that face this type of therapy is that cancer cells can evade immune system elimination through different mechanisms. Many studies were done to overcome this issue including adding immune stimulants to generate synergistic effects or by genetically modifying NK cells themselves to be stronger and more resistant.

Recent advances in photothermal therapy-based multifunctional nanoplatforms for breast cancer.

Breast cancer (BC) is one of the most common cancers in women worldwide however, the successful treatment of BC, especially triple-negative breast cancer (TNBC), remains a significant clinical challenge. Recently, photothermal therapy (PTT), which involves the generation of heat under irradiation to achieve photothermal ablation of BC with minimal invasiveness and outstanding spatial-temporal selectivity, has been demonstrated as a novel therapy that can overcome the drawbacks of chemotherapy or surgery. Significantly, when combining PTT with chemotherapy andor photodynamic therapy, an enhanced synergistic therapeutic effect can be achieved in both primary and metastatic BC tumors. Thus, this review discusses the recent developments in nanotechnology-based photothermal therapy for the treatment of BC and its metastasis to provide potential strategies for future BC treatment.

Comparison of Patients Phenotypes, Guideline-Directed Recommendations Compliance and Rates of Cardiotoxicity between Caribbean and United States Cardio-oncology Programs.

Little is known about the characteristics of oncological patients, cancer therapy-induced cardiotoxicity, and guidelines-directed interventions in the Caribbean analysis of cardio-oncology services may shed light on this and clarify links between ethnicity, cultural, and local socioeconomic factors. This study compared patients phenotypes, adherence to guidelines recommendations, and patterns of cardiotoxicity between two cardio-oncology programs one in the Dominican Republic (DR) and the other in Chicago IL, United States (US). Patients being considered for or treated with potentially cardiotoxic drugs were followed before, during, and after chemotherapy through both cardio-oncology clinics, where we recorded and compared clinical, demographic, and echocardiographic data. We studied 597 consecutive patients, 330 (55%) from the DR and 267 (45%) from the US. DR vs. US mean age 55± 1352 ± 13 years female 7787% (p < 0.001) breast cancer 5773% (p < 0.001) treated with anthracyclines taxanes 4740% (p 0.151) monoclonal antibodies taxanes or platins 3745% (p < 0.001). Cardiotoxicity DR vs. US occurred in 157% (p 0.001) multivariate logistic regression (OR 2.29 95% CI, 1.31-3.99 p < 0.005) did not identify age >60, HTN, DM, BMI, tobacco or chemotherapy as predictors. Compliance with ASCO guidelines was similar among both cohorts. Compared to the US cohort, the Caribbean cohort of cancer patients has similar rates of CV risk factors but a higher likelihood of developing drug-induced LV dysfunction. Programs compliance with ASCO guidelines was equivalent. While further research is needed to ascertain regional variations of cardiotoxicity, these findings underline the relevance of cardio-oncology services in nations with limited resources and high CV risk.

Antitumor Potential of Sericite Treatment Mediated by Cell Cycle Arrest in Triple-Negative MDA-MB231 Breast Cancer Cells.

Breast cancer is the most common cancer and the leading cause of cancer-related mortality among females worldwide. Triple-negative breast cancer (TNBC) accounts for about 10-15% of all breast cancers and is usually more aggressive and has a poorer prognosis. Sericite has been known to have antitumor and immune-stimulatory effects. Although the chemopreventive potential of sericite has been demonstrated in other cancers, its molecular pathways in TNBC still require investigation. Thus, in the present study, the antitumor mechanism of sericite against MDA-MB231 breast cancer cells was examined

Clinical value of next-generation sequencing in guiding decisions regarding endocrine therapy for advanced HR-positiveHER-2-negative breast cancer.

The mechanism of acquired gene mutation plays a major role in resistance to endocrine therapy in hormone receptor (HR)-positive advanced breast cancer. Circulating tumor DNA (ctDNA) has been allowed for the assessment of the genomic profiles of patients with advanced cancer. We performed this study to search for molecular markers of endocrine therapy efficacy and to explore the clinical value of ctDNA to guide precise endocrine therapy for HR-positivehuman epidermal growth factor receptor-2 (HER-2)-negative metastatic breast cancer patients. In this open-label, multicohort, prospective study, patients were assigned to four parallel cohorts and matched according to mutations identified in ctDNA 1) activation of the phosphatidylinositol-3-kinase (PI3K)AKTmammalian target of rapamycin (mTOR) signaling pathway preferred mTOR inhibitor combined with endocrine therapy 2) estrogen receptor 1 (ESR1) mutation preferred fulvestrant 3) HER-2 mutations preferred pyrotinib and 4) no actionable mutations received treatment according to the clinical situation. In all cohorts, patients were divided into compliance group and violation group. The primary outcome measure was progression-free survival (PFS), and the secondary outcome measure was overall survival (OS). In all cohorts, the combined median PFS was 4.9 months, and median PFS for the compliance and violation groups was 6.0 and 3.0 months, respectively P0.022, hazard ratio (HR)0.57. Multivariate Cox regression model showed the risk of disease progression was lower in compliance group than in violation group (P0.023, HR0.55). Among the patients with HER-2 mutations, the median PFS was 11.1 months in the compliance group and 2.2 months in the violation group (P0.011, HR0.20). There was no significant difference in the median PFS between patients who did and did not comply with the treatment protocol in patients with activation of the PI3KAKTmTOR or ESR1 mutation. The results suggest that ctDNA may help to guide the optimal endocrine therapy strategy for metastatic breast cancer patients and to achieve a better PFS. Next-generation sequencing (NGS) detection could aid in distinguishing patients with HER-2 mutation and developing new treatment strategies.

Timely Genetic Testing and Therapy Management in Patients With g

Talazoparib is a poly(ADP-ribose) polymerase (PARP) inhibitor that has demonstrated strong efficacy with manageable side effects for patients with germline breast cancer susceptibility genes 1 or 2 (g

Management of Adverse Events in Early Clinical Trials by Advanced Practice Providers in the Outpatient Setting The University of Texas MD Anderson Cancer Center Experience.

Advanced practice providers (APPs) play important roles in enrolling, educating, and caring for patients in clinical trials. However, much remains unknown about the role of APPs in managing adverse events (AEs) in early (phase I to II) clinical trials. In this study, we assessed the outpatient management of grade 3 to 4 AEs by APPs in early trials and characterized the workflow of our APP Phase I to II Fast Track (FT) Clinic. We retrospectively reviewed records of patients with advanced or metastatic solid tumors enrolled in phase I to II clinical trials who were seen by APPs from September 2017 to August 2018 in the APP phase I to II FT clinic in the Department of Investigational Cancer Therapeutics. A total of 808 patients enrolled in 159 clinical trials were seen in 2,697 visits (median 3 visits per patient range 1-28) by 10 APPs. Treatment was interrupted in 6.9% of visits, and grade 3 to 4 AEs were seen in 5.4% of visits however, patients from 1.4% of visits were sent to the emergency center (EC) andor admitted. Patients referred to the EC andor admitted were more likely to have baseline hypoalbuminemia, high lactate dehydrogenase, and poor Eastern Cooperative Oncology Group performance status (i.e., ECOG > 1 The APP Phase I to II FT Clinic has an important role in the management of AEs by APPs in early clinical trials in the outpatient setting, potentially avoiding EC visits and admissions.

Impact of Medicaid Expansion Under the Affordable Care Act on Receipt of Surgery for Breast Cancer.

To determine whether Medicaid expansion under the 2010 Affordable Care Act affected rates of breast cancer surgery. Data regarding the impact of Medicaid expansion on access to surgical treatment of breast cancer are limited. Patients in the National Cancer Database diagnosed with non-metastatic breast cancer between January 1, 2010 and December 31, 2017 and residing in a state that expanded Medicaid in January 2014 or in a state that opted out of expansion were included. A quasi-experimental, difference-in-differences (DID) approach was used to assess rate of omission of surgical treatment. Of 624,237 patients diagnosed with invasive breast cancer, 24,728 (4%) patients did not undergo surgical treatment. Overall, no significant differences in rates of omission of surgery over time were seen based on Medicaid expansion status. Significant findings were noted based on patient residential location. In rural areas, Medicaid expansion was associated with lower rates of omission of surgery (adjusted DID -2.47%, 95% confidence interval CI -4.01% to -0.94% Medicaid expansion had no measurable effect on the receipt of surgery for breast cancer in the overall cohort. Medicaid expansion was associated with higher rates of surgery in rural areas, representing the minority of the population.

CASP9 As a Prognostic Biomarker and Promising Drug Target Plays a Pivotal Role in Inflammatory Breast Cancer.

Inflammatory breast cancer (IBC) is one of the most rare and aggressive subtypes of primary breast cancer (BC). Our study aimed to explore hub genes related to the pathogenesis of IBC, which could be considered as novel molecular biomarkers for IBC diagnosis and prognosis. 157 DEGs were selected in total. We constructed the PPI network with 154 nodes interconnected by 128 interactions. The KEGG pathway analysis indicated that the DEGs were enriched in apoptosis, pathways in cancer and insulin signaling pathway. PTEN, PSMF1, PSMC6, AURKB, FZR1, CASP9, CASP6, CASP8, BAD, AKR7A2, ZNF24, SSX2IP, SIGLEC1, MS4A4A, and VSIG4 were selected as hub genes based on the high degree of connectivity. Six hub genes (PSMC6, AURKB, CASP9, BAD, ZNF24, and SSX2IP) that were significantly associated with the prognosis of breast cancer. The expression of CASP9 protein was associated with prognosis and immune cells infiltration of breast cancer. CASP9- naringenin (NGE) is expected to be the most promising candidate gene-compound interaction for the treatment of IBC. Taken together, CASP9 can be used as a prognostic biomarker and a novel therapeutic target in IBC.

Menopause is a normal event characterized by a drop in estrogens production, leading to numerous symptoms. To face these later, women rely on hormone replacement therapy (HRT), which alleviates numerous menopausal symptoms. Unfortunately, long-term exposure to estrogens is associated with an increase in endometrial and breast cancers. This study dealt with the evaluation of The The

Calcification, Posterior Acoustic, and Blood Flow Ultrasonic Characteristics of Triple-Negative Breast Cancer.

Previous studies suggest that triple-negative breast cancer (TNBC) may have unique imaging characteristics, however, studies focused on the imaging characteristics of TNBC are still limited. The aim of the present study is to analyze the ultrasonic characteristics of TNBC and to provide more reliable information on imaging diagnosis of TNBC. This retrospective study was performed including 162 TNBC patients with 184 TNBC lesions. 174 non-TNBC cases with 196 lesions were used as the control group. The median size of TNBC lesions and non-TNBC lesions were 23 mm × 16 mm and 21 mm × 15 mm, respectively. The shape of most breast cancer lesions was irregular. However, 15.30% (28183) TNBC lesions and 16.84% (33196) non-TNBC lesions were oval-shaped. Most breast cancer lesions (79.78% TNBC 85.71% non-TNBC) were ill-defined. In comparison to non-TNBC, the distinctive ultrasonic characteristics of TNBC were summarized as three features calcifications, posterior acoustic, and blood flow. Microcalcifications was less common in non-TNBC. The remarkable posterior acoustic characteristics on TNBC were no posterior acoustic features (136, 73.91%). Avascular pattern (21.74%) was also more common in TNBC. The other feature of TNBC was markedly hypoechoic lesions (23.91%). The above-mentioned differences between TNBC and non-TNBC were significant. 93.48% TBNC and 94.39% non-TNBC lesions were in BI-RADS-US category of 4A-5. The results indicate that TNBC has some distinctive ultrasound characteristics. Ultrasound is a useful adjunct in early detection of breast cancer. A combination of ultrasound with mammography is excellent for detecting breast cancer.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, with a high mortality rate. One of the main reasons for this poor prognosis is the failure of a specific diagnosis. As a tumor-homing and penetrating peptide, iRGD has not only the properties of binding to neuropilin-1 and integrin αvβ3 but also internalizing into TNBC cells. In this study, we designed and prepared

Retraction Long non-coding RNA PVT1 facilitates cell proliferation by epigenetically regulating FOXF1 in breast cancer.

This retracts the article DOI 10.1039C7RA12042G..

Efficacy and Safety of Pyrotinib in Human Epidermal Growth Factor Receptor 2-Positive Advanced Breast Cancer A Multicenter, Retrospective, Real-World Study.

Pyrotinib, a novel human epidermal growth factor receptor 2 (HER2)-targeted tyrosine kinase inhibitor (TKI), has led to remarkable survival outcomes in HER2-positive advanced breast cancer (ABC) in clinical trials and was approved for second-line standards of treatment for HER2 ABC in China. However, the clinical trials could not fully reflect reality of clinical practice, and predictive factors were still lacking. This study aimed to assess the actual efficacy and safety of pyrotinib in HER2 ABC in real-world setting. In this multicenter, retrospective, observational real-world study, we analyzed 171 patients with HER2 ABC, who received pyrotinib-based treatment from November 2017 to November 2020. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR) and safety. Up to November 30, 2021, the median PFS (mPFS) was 12.0 months for all patients. One hundred and sixty-two patients (94.7%) with measurable lesions had been included in efficacy assessment. The ORR and CBR were 45.1% and 81.5%, respectively. A significantly longer PFS was reported in patients who received pyrotinib as first-line treatment, had the ECOG-PS of 0-1, as well as those who were lapatinib-naive. In addition, multivariable analysis indicated that ECOG-PS of 2-4, positive hormone receptor (HR) status, and presence of visceral metastasis were independent negative predictors of PFS. As far as we know, this study first reported the survival outcome of pyrotinib cross-line treatment, with a mPFS of 5.0 months. All grades of adverse events (AEs) occurred in 171 patients (100%), and the most common AE was diarrhea (86.5%). This study further demonstrated the outstanding efficacy and safety of pyrotinib and reported the potential predictors of survival in HER2 ABC.

Effectiveness of breast cancer screening interventions in improving screening rates and preventive activities in Muslim refugee and immigrant women A systematic review and meta-analysis.

To systematically assess the effectiveness of breast cancer (BC) interventions in improving breast self-examination (BSE), clinical breast examination (CBE), mammogram screening rates, and preventive activities in Muslim refugee and immigrant women. Guided by the Health Belief Model, a mixed method systematic review and meta-analysis was performed using a sequential design. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement (PRISMA), the Critical Appraisal Skill Program Checklists, and the Joanna Briggs Institute (JBI) methodology for systematic review and meta-analysis. A systematic search of English-language peer-reviewed articles was undertaken in multiple health and social sciences databases from January 1, 2015, to March 31, 2022. Randomized clinical trials and quasi-experimental studies focused on the uptake of BSE, CBE, and mammograms were selected. Fourteen articles were included in the review. Most of the studies relied on quasi-experimental designs and were carried out in the United States of America. The qualitative analysis of BC screening interventions generated three themes (1) education, (2) access-focused, and (3) cultural and faith-based. The meta-analysis included three randomized control trials and two quasi-experimental studies. The meta-analysis demonstrates the effectiveness of community-led cultural and faith-based interventions in facilitating the completion of CBE and mammography screening. Education on BC and patient navigator interventions are more effectively used in conjunction than standalone interventions, yet community-based cultural and faith-based interventions are the most effective. This systematic and meta-analysis review provides evidence on the effectiveness of access-focused and cultural and faith-based interventions in improving BC screening in Muslim refugee and immigrant women. Future research should focus on designing and measuring the effectiveness of cultural and faith-based interventions to increase Muslim refugee and immigrant womens BC screening knowledge and practices. This systematic and meta-analysis review demonstrates the need to explore Muslim refugee and immigrant womens cultural contexts for developing culturally sensitive BC screening interventions. Knowledge and practice of BC and religiosity intersect with financial, geographic, and linguistic barriers to decrease participation in screening and preventive activities in Muslim refugee and immigrant women.

Integrated interventions and supporting activities to increase uptake of multiple cancer screenings conceptual framework, determinants of implementation success, measurement challenges, and research priorities.

Screening for colorectal, breast, and cervical cancer has been shown to reduce mortality however, not all men and women are screened in the USA. Further, there are disparities in screening uptake by people from racial and ethnic minority groups, people with low income, people who lack health insurance, and those who lack access to care. The Centers for Disease Control and Prevention funds two programs-the Colorectal Cancer Control Program and the National Breast and Cervical Cancer Early Detection Program-to help increase cancer screenings among groups that have been economically and socially marginalized. The goal of this manuscript is to describe how programs and their partners integrate evidence-based interventions (e.g., patient reminders) and supporting activities (e.g., practice facilitation to optimize electronic medical records) across colorectal, breast, and cervical cancer screenings, and we suggest research areas based on implementation science. We conducted an exploratory assessment using qualitative and quantitative data to describe implementation of integrated interventions and supporting activities for cancer screening. We conducted 10 site visits and follow-up telephone interviews with health systems and their partners to inform the integration processes. We developed a conceptual model to describe the integration processes and reviewed screening recommendations of the United States Preventive Services Task Force to illustrate challenges in integration. To identify factors important in program implementation, we asked program implementers to rank domains and constructs of the Consolidated Framework for Implementation Research. Health systems integrated interventions for all screenings across single and multiple levels. Although potentially efficient, there were challenges due to differing eligibility of screenings by age, gender, frequency, and location of services. Program implementers ranked complexity, cost, implementation climate, and engagement of appropriate staff in implementation among the most important factors to success. Integrating interventions and supporting activities to increase uptake of cancer screenings could be an effective and efficient approach, but we currently do not have the evidence to recommend widescale adoption. Detailed multilevel measures related to process, screening, and implementation outcomes, and cost are required to evaluate integrated programs. Systematic studies can help to ascertain the benefits of integrating interventions and supporting activities for multiple cancer screenings, and we suggest research areas that might address current gaps in the literature.

Optimism and symptoms of anxiety and depression among Chinese women with breast cancer the serial mediating effect of perceived social support and benefit finding.

This research examines the direct and indirect relationships between optimism, perceived social support (PSS), benefit finding (BF), and anxiety and depressive symptoms among Chinese women with breast cancer (BC). We recruited 512 patients, aged averagely 47.46(SD 8.51) years from two hospitals located in Hunan province, China. The variables were assessed using the Optimism-Pessimism Scale (OPS), the Multidimensional Scale of Perceived Social Support (MSPSS), the Benefit Finding Scale (BFS), and the Hospital Anxiety and Depression Scale (HADS). Path analyses were conducted by Amos version 24.0 for Windows to test the hypothesized serial mediation model. Path analyses suggest a significant negative association between optimism and symptoms of anxiety and depression. The relationship was mediated by BF (β -0.085, SE 0.015, 95% CI -0.126, -0.055), and by BF together with PSS (β -0.027, SE 0.007, 95% CI -0.047, -0.017). The difference comparison between the two indirect effects was significant (β 0.057, SE 0.015, 95% CI 0.034,0.101). Our findings suggest that PSS, and BF are important mediators through which optimism may buffer symptoms of anxiety and depression among Chinese BC patients. Clinicians and healthcare practitioners should be aware of the importance of patients emotional health and endeavor to offer emotional support, facilitate their capacity to improve their quality of life.

Patient-centered dosing oncologists perspectives about treatment-related side effects and individualized dosing for patients with metastatic breast cancer (MBC).

Although metastatic breast cancer (MBC) is treatable, it is not curable and most patients remain on treatment indefinitely. While oncologists commonly prescribe the recommended starting dose (RSD) from the FDA-approved label, patient tolerance may differ from that seen in clinical trials. We report on a survey of medical oncologists perspectives about treatment-related toxicity and willingness to discuss flexible dosing with patients. We disseminated a confidential survey via social mediaemail in Spring 2021. Eligible respondents needed to be US-based medical oncologists with experience treating patients with MBC. Of 131 responses, 119 were eligible. Physicians estimated that 47% of their patients reported distressing treatment-related side effects of these, 15% visited the Emergency Roomhospital and 37% missed treatment. 74% (n 87) of doctors reported improvement of patient symptoms after dose reduction. 87% (n 104) indicated that they had ever, if appropriate, initiated treatment at lower doses. Most (85%, n 101) respondents did not believe that the RSD is always more effective than a lower dose and 97% (n 115) were willing to discuss individualized dosing with patients. Treatment-related side effects are prevalent among patients with MBC, resulting in missed treatments and acute care visits. To help patients tolerate treatment, oncologists may decrease initial andor subsequent doses. The majority of oncologists reject the premise that a higher dose is always superior and are willing to discuss individualized dosing with patients. Given potential improvements regarding quality of life and clinical care, dose modifications should be part of routine shared decision-making between patients and oncologists.

Genome engineering for estrogen receptor mutations reveals differential responses to anti-estrogens and new prognostic gene signatures for breast cancer.

Mutations in the estrogen receptor (ESR1) gene are common in ER-positive breast cancer patients who progress on endocrine therapies. Most mutations localise to just three residues at, or near, the C-terminal helix 12 of the hormone binding domain, at leucine-536, tyrosine-537 and aspartate-538. To investigate these mutations, we have used CRISPR-Cas9 mediated genome engineering to generate a comprehensive set of isogenic mutant breast cancer cell lines. Our results confirm that L536R, Y537C, Y537N, Y537S and D538G mutations confer estrogen-independent growth in breast cancer cells. Growth assays show mutation-specific reductions in sensitivities to drugs representing three classes of clinical anti-estrogens. These differential mutation- and drug-selectivity profiles have implications for treatment choices following clinical emergence of ER mutations. Our results further suggest that mutant expression levels may be determinants of the degree of resistance to some anti-estrogens. Differential gene expression analysis demonstrates up-regulation of estrogen-responsive genes, as expected, but also reveals that enrichment for interferon-regulated gene expression is a common feature of all mutations. Finally, a new gene signature developed from the gene expression profiles in ER mutant cells predicts clinical response in breast cancer patients with ER mutations.

Deep learning radiomics under multimodality explore association between musclefat and metastasis and survival in breast cancer patients.

Sarcopenia is correlated with poor clinical outcomes in breast cancer (BC) patients. However, there is no precise quantitative study on the correlation between body composition changes and BC metastasis and survival. The present study proposed a deep learning radiomics (DLR) approach to investigate the effects of muscle and fat on distant metastasis and death outcomes in BC patients. Image feature extraction was performed on 4th thoracic vertebra (T4) and 11th thoracic vertebra (T11) on computed tomography (CT) image levels by DLR, and image features were combined with clinical information to predict distant metastasis in BC patients. Clinical information combined with DLR significantly predicted distant metastasis in BC patients. In the test cohort, the area under the curve of model performance on clinical information combined with DLR was 0.960 (95% CI 0.942-0.979, P < 0.001). The patients with distant metastases had a lower pectoral muscle index in T4 (PMIT4) than in patients without metastases. PMIT4 and visceral fat tissue area in T11 (VFAT11) were independent prognostic factors for the overall survival in BC patients. The pectoralis muscle area in T4 (PMAT4) and PMIT4 is an independent prognostic factor for distant metastasis-free survival in BC patients. The current study further confirmed that musclefat of T4 and T11 levels have a significant effect on the distant metastasis of BC. Appending the network features of T4 and T11 to the model significantly enhances the prediction performance of distant metastasis of BC, providing a valuable biomarker for the early treatment of BC patients.

A Neutral and Stable Macrocyclic Mn(II) Complex for MRI Tumor Visualization.

A stable and inert amphiphilic Mn(II) complex based on a bisamide derivative of 1,4-DO2A (DO2Atetraazacyclododecane-1,4-diacetic acid) was synthesized and its

Person-centred support programme (RESPECT intervention) for women with breast cancer treated with endocrine therapy a feasibility study.

The peRson-cEntred Support Programme EndoCrine Therapy intervention is a complex intervention encompassing a person-centred support programme for patients with breast cancer being treated with endocrine therapy (ET). The aim of this study was to explore the feasibility of the trial design and patient acceptability of the intervention and outcome measures and to provide data to estimate the parameters required to design the final intervention. A controlled before-and-after design following the Consolidated Standards of Reporting Trials 2010 statement for feasibility trials. A surgical outpatient clinic in Sweden. Forty-one patients (aged 47-85) with breast cancer who were treated with ET. Eligible patients were assigned to the control group or intervention group, which included individual education material, an individualised learning plan and a personalised reminder letter using a person-centred approach. The intervention could be delivered as a telephone or digital follow-up during a 12-week follow-up. The aims were to determine the recruitment rate, assess the rate of retention, explore whether the intervention was delivered according to the protocol, assess the preferred form of educational support, rate of education sessions, length per education session and length between each education session, determine the distribution of education materials and assess completion rates of patient-reported instruments, including the General Self-efficacy Scale, the Quality of Care from the Patients Perspective Questionnaire and the Memorial Symptom Assessment Scale. Eighty-six per cent of the patients in the intervention group completed the intervention and questionnaires 3 months after their inclusion. The call attendance was 90%. During the intervention, the contact nurse complied with the intervention protocol. For self-efficacy, symptoms and quality of care, there were no differences in effect size between the control and intervention groups. This intervention seems to be feasible and acceptable among patients.

Development of a Mobile-Based Self-care Application for Patients with Breast Cancer-Related Lymphedema in Iran.

Due to the chronic, progressive, and debilitating nature of breast cancer-related lymphedema (BCRL), it is necessary to observe and maintain self-care management accordingly. This study was conducted to develop a mobile application based on the Android operating system for self-care management of Iranian patients with BCRL. An applied developmental study was conducted in 2020. The users information needs assessment as well as design, development, implementation, and evaluation of the mobile app for self-care management of patients with BCRL was done by searching the literature, reviewing the existing mobile applications, and surveying the users needs. The mobile app was designed using the Android Studio environment and Java programming language in the Android operating system. The usability of the app was evaluated by 30 patients with BCRL using the questionnaire for user interface satisfaction-seventh version (QUIS 7). The mobile app for BCRL included demographic information, clinical information, lifestyle and system functions (drug use, nutrition, exercise, smoking cessation, communication, and test time reminder). User usability evaluation of the app content and functions confirmed that it was appropriate and satisfactory for the self-management of women with BCRL. The mobile app was appropriate in terms of the content, function, and quality for improving the patients lifestyle and education and self-management of BCRL symptoms according to its usability evaluation from the end-users (patients) perspective. It is suggested that studies should be performed to confirm the effectiveness and identify the clinical significance of the app.

Clinical Significance of Eligibility Criteria Determined by the SPIRITS Trial in Patients with Advanced Gastric Cancer.

This study aimed to assess the clinical significance of eligibility criteria determined by phase 3 clinical trials in the clinical practice of patients with advanced gastric cancer who underwent chemotherapy. Patients with stage IV gastric cancer who received chemotherapy between February 2002 and December 2021 were retrospectively enrolled and divided into two groups (the eligible vs. ineligible group) based on eligibility criteria determined by the SPIRITS (S-1 vs. S-1 plus cisplatin) trial. Among the 207 patients, 103 (49.8%) and 104 (50.2%) patients were classified into eligible and ineligible groups, respectively. Eligibility criteria were significantly correlated with age, the first-line regimen of chemotherapy, the presence or absence of conversion surgery, and tumor response to the first-line chemotherapy (all p < 0.01). The eligible group had a significantly higher induction of post-progression chemotherapy after first- and second-line chemotherapy than did the ineligible group (all p < 0.01). The ineligible group had significantly poorer prognoses than the eligible group (p < 0.0001). Multivariate analysis showed that peritoneal dissemination, tumor response, conversion surgery, and eligibility criteria were independent prognostic factors (all p < 0.05). Eligibility criteria determined by the SPIRITS trial may have clinical utility for predicting tumor response, the induction of conversion surgery, and prognosis in patients with advanced gastric cancer who underwent chemotherapy.

Determinants of mammography screening participation-a cross-sectional analysis of the German population-based Gutenberg Health Study (GHS).

We investigated the association between social inequality and participation in a mammography screening program (MSP). Since the German government offers mammography screening free of charge, any effect of social inequality on participation should be due to educational status and not due to the financial burden. The Gutenberg Health Study is a cohort study in the Rhine-Main-region, Germany. A health check-up was performed, and questions about medical history, health behavior, including secondary prevention such as use of mammography, and social status are included. Two indicators of social inequality (equivalence income and educational status), an interaction term of these two, and different covariables were used to explore an association in different logistic regression models. A total of 4,681 women meeting the inclusion criteria were included. Only 6.2% never participated in the MSP. A higher income was associated with higher chances of ever participating in a mammography screening (odds ratios (OR) 1.67 per €1000 95%CI1.26-2.25, model 3, adjusted for age, education and an interaction term of income and education). Compared to women with a low educational status, the odds ratios for ever participating in the MSP was lower for the intermediate educational status group (OR 0.64, 95%CI0.45-0.91) and for the high educational status group (0.53, 95%CI0.37-0.76). Results persisted also after controlling for relevant confounders. Despite the absence of financial barriers for participation in the MSP, socioeconomic inequalities still influence participation. It would be interesting to examine whether the educational effect is due to an informed decision.

Insulin resistance and racial disparities in breast cancer prognosis a multi-center cohort study.

The survival for breast cancer (BC) is improving but remains lower in Black women than White women. A number of factors potentially drive the racial differences in BC outcomes. The aim of our study was to determine if insulin resistance (defined as homeostatic model assessment for insulin resistance (HOMA-IR)), mediated part of the relationship between race and BC prognosis (defined by the improved Nottingham prognostic index (iNPI)). We performed a cross-sectional study, recruiting self-identified Black and White women with newly diagnosed primary invasive BC from 10 US hospitals between March 2013 and February 2020. Survey, anthropometric, laboratory, and tumor pathology data were gathered, and we compared the results between Black and White women. We calculated HOMA-IR as well as iNPI scores and examined the associations between HOMA-IR and iNPI. After exclusions, the final cohort was 1206 911 (76%) White and 295 (24%) Black women. Metabolic syndrome and insulin resistance were more common in Black than White women. Black women had less lobular BC, three times more triple-negative BC, and BCs with higher stage and iNPI scores than White women (P < 0.001 for all comparisons). Fewer Black women had BC genetic testing performed. HOMA-IR mediated part of the association between race and iNPI, particularly in BCs that carried a good prognosis and were hormone receptor (HR)-positive. Higher HOMA-IR scores were associated with progesterone receptor-negative BC in White women but not Black women. Overall, our results suggest that HOMA-IR contributes to the racial disparities in BC outcomes, particularly for women with HR-positive BCs.

A colorimetric aptasensor based on a heminEpCAM aptamer DNAzyme for sensitive exosome detection.

Exosomes are considered as potential biomarkers that can reflect information from their parent cell-associated cancer microenvironment. Recently, aptasensors have been widely used for cancer and tumor exosome detection. Aptamers related to exosome surface proteins are usually used to introduce a sequence the aptamer is used for exosome recognition, and the introduced sequence is used to form G-quadruplexes and for signal amplification. In this paper, we found that the EpCAM aptamer is rich in guanine and unimolecular G-quadruplex with a two-layer G-tetrad under acidic conditions, and we investigated its topology, thermal stability and dissociation constant with hemin. Based on this, our proposed colorimetric aptamer sensor combines the unmodified EpCAM aptamer with hemin to construct a heminG-quadruplex DNAzyme and catalyze the TMB-H

Association of Long-term Oncologic Prognosis With Minimal Access Breast Surgery vs Conventional Breast Surgery.

Minimal access breast surgery (MABS) has been used in breast cancer management. However, long-term prognostic data associated with MABS vs conventional breast surgery (CBS) are lacking. To investigate long-term therapeutic outcomes associated with MABS vs CBS for breast cancer management. In this single-center retrospective cohort study, 9184 individuals were assessed for inclusion. After exclusions, 2412 adult female individuals were included who were diagnosed with stage 0 to III breast cancer, underwent unilateral breast surgery between January 2004 and December 2017, and had no distant metastasis or history of severe underlying disease. Propensity score matching was performed to minimize selection bias. Data were analyzed from January 1, 2004, to December 31, 2019. MABS or CBS. Data on demographic and tumor characteristics and long-term outcomes were collected and analyzed. This study included 2412 patients (100% female median IQR age, 44 40-49 years). Of these, 603 patients underwent MABS (endoscopic, endoscopy-assisted, or robot-assisted procedures in 289, 302, and 12 patients, respectively) and 1809 patients underwent CBS. The median follow-up time was 84 months (93 in the MABS group and 80 months in the CBS group). Intergroup differences were not significant for the following parameters 10-year local recurrence-free survival (93.3% vs 96.3% hazard ratio HR, 1.39 95% CI, 0.86-2.27 P .18), regional recurrence-free survival (95.5% vs 96.7% HR, 1.38 95% CI, 0.81-2.36 P .23), and distant metastasis-free survival (81.0% vs 82.0% HR, 0.95 95% CI, 0.74-1.23 P .72). The 5-, 10-, and 15-year disease-free survival rates in the MABS group were 85.9%, 72.6%, and 69.1%, respectively. The corresponding rates in the CBS group were 85.0%, 76.6%, and 70.7%. The intergroup differences were not significant (HR, 1.07 95% CI, 0.86-1.31 P .55). The 5-, 10-, and 15-year overall survival rates in the MABS group were 92.0%, 83.7%, and 83.0%, respectively. The corresponding rates in the CBS group were 93.6%, 88.7%, and 81.0%. The intergroup differences were not significant (HR, 1.29 95% CI, 0.97-1.72 P .09). Post hoc subgroup analysis showed no significant intergroup differences in disease-free survival. In this cohort study, long-term outcomes following MABS were not significantly different from those following CBS in patients with early-stage breast cancer. MABS may be a safe and feasible alternative in this patient population.

Mesoporous silica coated SPIONs containing curcumin and silymarin intended for breast cancer therapy.

Super-paramagnetic iron oxide nanoparticles (SPIONs) are known as promising theranostic nano-drug carriers with magnetic resonance imaging (MRI) properties. Applying the herbaceous components with cytotoxic effects as cargos can suggest a new approach in the field of cancer-therapy. In this study mesoporous silica coated SPIONs (mSiO2SPIONs) containing curcumin (CUR) and silymarin (SIL) were prepared and evaluated on breast cancer cell line, MCF-7. Nanoparticles (NPs) were formulated by reverse microemulsion method and characterized by DLS, SEM and VSM. The in vitro drug release, cellular cytotoxicity, and MRI properties of NPs were determined as well. The cellular uptake of NPs by MCF-7 cells was investigated through LysoTracker Red staining using confocal microscopy. The MTT results showed that the IC50 of CUR SIL loaded mSiO2SPIONs was reduced about 50% in comparison with that of the free drug mixture. The NPs indicated proper MRI features and cellular uptake through endocytosis. In conclusion the prepared formulation may offer a novel theranostic system for breast cancer researches.

Breast cancer risk in Ukrainian women exposed to Chornobyl fallout while pregnant or lactating standardized incidence ratio analysis, 1998 to 2016.

The radiation-related risk of breast cancer among women following the Chornobyl accident remains uncertain. During pregnancy, there is rapid cell proliferation in the breast while radioactive iodine from fallout exposure can concentrate in lactating breast tissues. We conducted a standardized incidence ratio (SIR) analysis of breast cancer in a cohort of 2,631 women who were lactating andor pregnant at any time during the 2-month period of radioiodine fallout (April 26, 1986-June 30, 1986). There were 37,151 person-years of follow-up, and 26 incident breast cancers were identified through linkage with the National Cancer Registry of Ukraine. Breast cancer rates among pregnant or lactating women were compared to the general population rates, and SIRs were adjusted for oblast, urbanrural, age, and calendar year. The SIR was not significant for women pregnant at the time of the accident (SIR 0.75 95% CI 0.44, 1.18) or for women lactating anytime within 2 months of the accident (SIR 0.96 95% CI 0.48, 1.68). However, there was a non-significantly elevated risk for women lactating at the time of accident (SIR 1.30, 95% CI 0.40, 3.01). The increased SIR for breast cancer among lactating women is consistent with the results of a similar study in Belarus and indicates the need to quantify the radiation risk of breast cancer in a larger study of women lactating during the period of fallout exposure.

Design, combinatorial synthesis and cytotoxic activity of 2-substituted furo2,3-dpyrimidinone and pyrrolo2,3-dpyrimidinone library.

A facile protocol was developed for the combinatorial synthesis of furo2,3-dpyrimidinone and pyrrolo2,3-dpyrimidinone library via a one-pot condensation, from 2-amino furanspyrroles. Herein reported process required a similar reaction condition, providing mild access to two diverse series of natural product-like heterocycles. Both furo2,3-dpyrimidinones and pyrrolo2,3-dpyrimidinones were evaluated in vitro against a panel of human cancer cell lines including against human cancer HeLa (cervical), MCF-7 (breast) and HT-29 (colon) cell lines. Derivative 12n ((2-(4-chlorophenyl)-1-methyl-6,7,8,9-tetrahydropyrido1,2-apyrrolo2,3-dpyrimidin-4(1H)-one)) showed high activity (IC

Factors associated with worsening sexual function during adjuvant endocrine therapy in a prospective clinic-based cohort of women with early-stage breast cancer.

Sexual function problems are common but under-reported among women receiving adjuvant endocrine therapy for breast cancer. Worsening scores on patient-reported outcomes (PROs) may identify those at risk for sexual function problems during treatment. We performed a secondary analysis of prospectively collected PROs in women receiving adjuvant endocrine therapy to identify factors associated with worsening sexual function. Women with stage 0-III breast cancer initiating adjuvant endocrine therapy participating in a prospective cohort completed PROs at baseline, 3, 6, 12, 24, 36, 48, and 60 months. Sexual function was evaluated by the MOS-SP measure. Other measures included PROMIS pain interference, fatigue, depression, anxiety, physical function, and sleep disturbance and the Endocrine Symptom Subscale of the FACT-ES. We evaluated associations between score worsening of at least the minimal important difference (MID) in PROMIS T-scores (4 points) and FACT-ES scores (5 points) with score worsening of at least the MID in MOS-SP scores (8 points) using logistic regression. Among 300 participants, 45.7% experienced ≥ 8-point worsening of MOS-SP score at any time point compared to baseline. Worsening endocrine symptoms (OR 1.34, 95% CI 1.22-1.49, p < 0.001), worsening physical function (OR 1.09, 95% CI 1.00-1.18, p 0.06), and prior mastectomy (OR 1.45, 95% CI 0.94-2.23, p 0.09) were associated with MOS-SP score worsening by at least the MID. Worsening endocrine symptoms and physical function identified on PROs are associated with worsening sexual function during adjuvant endocrine therapy. Routine assessment of these domains with PROs may identify women at risk for sexual function problems. NCT01937052 Date of Registration 09092013.

Effects of preoperative personal education on shoulder function and lymphedema in patients with breast cancer A consort.

To compare the incidence and severity of ipsilateral shoulder dysfunction and lymphedema of 2 groups of patients needing to undergo unilateral breast cancer surgery, one of which had only received printed education materials and the other group which had received educational materials plus preoperative education. We selected 61 patients who had been diagnosed with unilateral breast cancer and planned to undergo surgery. Before surgery, patients were randomly assigned, either to a control group that only received printed education materials about exercise for shoulder pain relief and lymphatic edema prevention following breast cancer surgery, or to an experimental group that received the printed education material with personal education. Participants were evaluated at 1, 3, 6, and 12 months after the surgery. To evaluate the impairment of shoulder function, we measured the passive shoulder range of motion (ROM), the degree of pain as visual analog scale (VAS), the short version of the disability of arm, shoulder, and hand (short DASH) scores, and the shoulder pain and disability index (SPADI). We checked arm circumferences to evaluate lymphedema. There was no significant difference in demographic or clinical variables between the control and experimental groups. The experimental group showed significantly less limitation in abduction (P .042) and forward flexion (P .039) in the 6 months following surgery. Change in the VAS, short DASH, and SPADI scores were 1.633 (P < .001), 2.167 (P < .001), and 4.1 (P .003) at 1 month following surgery, respectively. These then decreased with time. These changes started before shoulder ROM and arm circumference changes had occurred, which had started 3 months following surgery. Preoperative education might be helpful for the prevention of a shoulder ROM limitation, and we need to focus on pain and disability in patients immediately following breast cancer surgery, and then on ROM and lymphedema.

Roles of activator protein-2 gamma in breast cancer A narrative review (SANRA).

Activator protein-2 gamma (AP-2γ) is a crucial transcription factor involved in breast cancer development. Abnormal expression and activity of AP-2γ have also been identified as important markers of malignancy. In the last decade, the importance of AP-2γ in breast cancer progression has been widely studied. In this review, we summarize the current knowledge on the regulatory roles of AP-2γ in breast cancer oncogenesis and progression and its potential as a diagnostic biomarker and drug target in breast cancer treatment.

Metastasis of the Mucionous adenocarcinoma of breast to the mandibular gingiva Rare case report.

Mucinous adenocarcinoma (MAC) is a rare type of cancer in which more than 50% of the tumor is composed of extracellular mucin and malignant epithelial cells. MACs account for only 1.8% of all breast cancer cases. Most breast cancers present as localized diseases and are well-differentiated. Breast MAC has a better 5- and 10-year survival rate than ductal and lobular carcinomas. Distant metastasis in breast MAC is rare, especially in the oral cavity. Only 1% of all oral malignancies present with metastases to the oral cavity. The bony structures are more involved than the soft tissues. Involvement of the oral soft tissue is rare, accounting for less than 0.1% of oral metastases. This report describes a rare case of mucinous breast adenocarcinoma with metastasis to the mandibular molar region. Diagnosis was established based on anamnesis, clinical presentation, tumor biopsy, computed tomography, mammography, and core biopsy of the breast tumor. The patient was sent to the oncology committee for breast disease where chemotherapy was indicated. The clinical presentation of oral metastasis is not pathognomonic, and pyogenic granuloma, periodontal abscesses, sarcomas, and squamous carcinoma must be considered in the differential diagnosis. This is a rare case of oral metastasis of breast MAC, which was indicated for detection of the primary tumor.

A bibliometric analysis of the top 100 most cited papers and research trends in breast cancer related BRCA1 and BRCA2 genes.

This study aimed to identify, characterize, and map the important attributes of the top 100 most cited papers on BRCA1 and BRCA2 genes. The scientific literature on BRCA1 and BRCA2 was searched in the Web of Science Core Collection database using the keywords BRCA1 OR BRCA2 (Title). The top 100 most cited papers were selected based on citations. The obtained data were exported into HistCiteTM, RStudio, and VOSviewer software for prerequisite analysis. The top 100 most cited papers on BRCA1 and BRCA2 were authored by 932 authors from 24 countries and published in 27 journals. These papers were cited 79,713 times, ranging from 441 to 4671 citations. The highly cited paper was cited 4671 times and published in Science (1994). The leading author, journal, publication year, institution, and country were Easton DF (n 16), Nature Genetics (n 11), 2002 (n 11), University of Pennsylvania (n 17), and the USA (n 76), respectively. The results show that all the top 100 papers were produced in developed countries. The collaboration index among the authors was 9.49. The most frequently appeared keywords were ovarian-cancer, breast-cancer, mutations, gene, and familial breast. In recent times, the trend topics were patients, mutations, carriers, ovarian, and risk.

Ulleungdolin, a Polyketide-Peptide Hybrid Bearing a 2,4-Di-

A new secondary metabolite, ulleungdolin (

TRIM35 ubiquitination regulates the expression of PKM2 tetramer and dimer and affects the malignant behaviour of breast cancer by regulating the Warburg effect.

Breast cancer has become the leading cause of death in females. After comprehensive treatment, the lives of patients are still threatened by tumor metastasis and recurrence. Therefore, there is an urgent requirement to find an effective treatment target for breast cancer. Tripartite motif‑containing 35 (TRIM35) is a ubiquitin ligase that has an important role in the recurrence and metastasis of malignant tumors. However, the role of TRIM35 in breast cancer has thus far remained elusive. The expression of TRIM35 was examined in a bioinformatics database and the effects of TRIM35 on the malignant biological behavior of breast cancer were analyzed by Cell Counting Kit‑8, cell migration and invasion assays, flow cytometry and nude mouse xenograft experiments. It was determined that TRIM35 was downregulated in breast cancer tumor tissues and cell lines. Patients with low TRIM35 expression had shorter overall survival. Functional assays revealed that overexpression of TRIM35 inhibited the proliferation, migration and invasion, and promoted apoptosis of breast cancer cells. Furthermore, overexpression of TRIM35 was able to inhibit the Warburg effect in breast cancer cells. Mechanistic analyses indicated that TRIM35 regulates the transition of tetramers and dimers of pyruvate kinase M2 (PKM2) through ubiquitination and thereby affects the Warburg effect. In conclusion, the present results indicated that TRIM35 regulates the tetramer and dimer transition of PKM2 through ubiquitination and affects the malignant biological behavior of breast cancer by modulating the Warburg effect.

Challenges of expert assessment of injury to health in the case of iatrogenic mastectomy due to erroneous histological verification of an oncological condition.

A case of commission forensic medical examination in the St. Petersburg Bureau of Forensic Science of a civil case due to an unfavorable treatment outcome is presented. Patient Представлен случай проведения в СПб ГБУЗ» комиссионной судебно-медицинской экспертизы по гражданскому делу в связи неблагоприятным исходом лечения. Пациентка

Retraction Note LncRNA RUSC1-AS1 promotes the proliferation of breast cancer cells by epigenetic silence of KLF2 and CDKN1A.

The article LncRNA RUSC1-AS1 promotes the proliferation of breast cancer cells by epigenetic silence of KLF2 and CDKN1A, by C.-C. Hu, Y.-W. Liang, J.-L. Hu, L.-F. Liu, J.-W. Liang, R. Wang, published in Eur Rev Med Pharmacol Sci 2019 23 (15) 6602-6611-DOI 10.26355eurrev20190818548-PMID 31378902 has been retracted by the authors. After publication, the article was questioned on PubPeer. Concerns were raised about Figure 2, Table I, and the reliability of the published results. The same authors stated that they want to rearrange the manuscript and provide readers with a more precise model. httpswww.europeanreview.orgarticle18548.

Multidisciplinary management of mammary Pagets disease recommendations to optimize oncological and aesthetic outcomes.

We read with interest the article of Francesca Maria Plutino entitled A peculiar case of Pagets disease of the breast and would like to make some considerations about this particular topic 1. Mammary Pagets Disease (MPD) or Pagets disease of the breast is an uncommon pathology which accounts for less than 5% of breast cancers 1-3. MPD occurs with alterations of the nipple-areolar complex (NAC) such as redness, eczema, bleeding ulceration and usually itching 1-3. In the era of personalized care, a careful multidisciplinary management is mandatory to optimize the results and minimize the risk of overtreatment 4 an adequate knowledge of the MPD, surgical skills and use of appropriate adjuvant therapies allow to reduce the risk of local recurrence and improve the aesthetic outcomes and patients quality of life however, a successful work can be more easily achieved thanks to the repetitive performance of some standardized tasks, such as 5 - an accurate radiological preoperative assessment with mammography and ultrasonography is important to identify associated glandular lesions an underlying breast carcinoma (in situ andor invasive) may be present up to about 80% to 90% of MPD although often without an evident breast mass or mammographic abnormality (2,5) therefore, all patients with MPD should also perform a magnetic resonance imaging to detect possible underlying occult breast carcinoma and define the true extent of disease 5,6 - a pathological diagnosis should be early established by nipple scrape cytology when a MPD is clinically suspected full-thickness punch or wedge biopsy of the NAC may be necessary to accurately diagnose MPD the histological examination must detect malignant intraepithelial carcinoma cells, also known as Paget cells, in the epidermis of the NAC 2,3 a needle biopsy is also required for any suspicious glandular lesion identified by imaging and associated with MPD 5 - a multidisciplinary Surgery Board is mandatory to select the more adequate local treatment for the patient breast-conserving surgery (BCS) followed by radiotherapy (RT) is the optimal local treatment when a NAC resection and wide local excision of any underlying cancer allows to achieve tumour-free margins and appropriate aesthetic outcomes 4,5,7 the oncoplastic techniques with the remodelling of breast tissue and placement of clips within the excision cavity as a landmark to guide adjuvant RT should always be used in BCS in order to optimize oncological and cosmetic results 5,8,9,10. Instead, skin-sparing mastectomy with immediate breast reconstruction is indicated for MPD associated to multicentric or extensive carcinoma, inadequate margins after BCS, contraindications to adjuvant RT and patient preference 5,8. Staging and surgical treatment of the axilla in MPD is based on the possible presence of underlying cancer sentinel lymph node biopsy (SLB) is not necessary when BCS is used to treat pure MPD or MPD associate with ductal carcinoma in situ SLB must be performed when MPD is associated with underlying invasive cancer and treated with breast-conserving surgery SLB is always recommended when a mastectomy is performed in order to avoid complete axillary lymph node dissection in case an invasive component is revealed at final pathology of the gland (mastectomy precludes subsequent use of SLB) 5,7,8 - a multidisciplinary Tumor Board is crucial to choose the adjuvant treatment whole breast radiation should be always performed after BCS and a radiation boost should be considered for the site of the resected NAC and any associated resected cancer site 2,4,5 adjuvant systemic therapies in patients with MPD should be based on biological features and the stage of the underlying cancer no data are available to support the use of endocrine therapy in the MPD without an associated DCIS or invasive carcinoma 5. In conclusion, a dedicated multidisciplinary pathway with meticulous repetitive performance of some specific tasks could help to perform a successful work while optimizing oncological and aesthetic outcomes in patients with MPD.

Understanding pain related to adjuvant endocrine therapy after breast cancer A qualitative report.

Most patients report pain while taking adjuvant endocrine therapy (AET) for the treatment of breast cancer. While studies have examined patients experiences with side effects, none solely capture patients experiences with AET-related pain, a troubling symptom that reduces quality of life and impairs treatment adherence. This study explored themes of AET-related pain to inform future intervention development. Between November 2017 and November 2018, female patients (n 30) with early-stage breast cancer enrolled between 3 and 36 months post-initiation of AET. Purposeful sampling was stratified by adherence level, age, distress level and time taking AET. Study staff conducted, transcribed and coded semi-structured interviews via inductive thematic coding to identify pain-related themes and achieved high inter-coded reliability (Kappa 0.96). Several pain-related themes were observed. Attitudes around pain are generally negative, and management needs are largely unmet. Patients reported preferences for non-pharmacological management strategies and cited AET pain as a reason for medication breaks but not discontinuation. Patients within 19 months of starting AET and low adherers reported more intense and disruptive pain. Patients experiences varied by patient attributes and revealed modifiable factors that may be targeted through behavioural interventions. AET-related pain is a complex side effect for which psychosocial support may be beneficial.

Incidence of cancer among Nordic police officers.

Police work may expose officers to various circumstances that have potential for increasing their risk of cancer, including traffic-related air pollution, night shift work and radiation from radars. In this study, we examined the incidence of cancer among Nordic male and female police officers. We utilize data from the Nordic Occupational Cancer (NOCCA) project, which linked census data on occupations from Finland, Iceland, Norway and Sweden to national cancer registries for the period 1961 to 2005. We report standardized incidence ratios (SIR) and 95% confidence intervals (CI) of selected cancers for each country by sex, age and calendar period. The cohort included 38 523 male and 1998 female police officers. As compared with the general population, male police officers had a 7% (95% CI 4-9%) excess cancer risk, with elevated SIRs for various cancer sites, including prostate (SIR 1.19, 1.14-1.25), breast (SIR 1.77, 1.05-2.80), colon (SIR 1.22, 1.12-1.32) and skin melanoma (SIR 1.44, 1.28-1.60). Conversely, male police officers had a lower risk of lung cancer than the general population (SIR 0.72, 0.66-0.77). In female police officers, the SIR for cancer overall was 1.15 (0.98-1.34), and there was a slight excess of cancers of the breast (SIR 1.25, 0.97-1.59) and colon (SIR 1.21, 0.55-2.30). In conclusion, cancer incidence among the police officers was slightly higher than in the general population. Notably, SIRs were elevated for cancer sites potentially related to night shift work, namely colon, breast and prostate cancer.

Deep inspiration breath hold in post-operative radiotherapy for right breast cancer a retrospective analysis.

The aim of our study is to determine whether deep inspiration breath hold (DIBH) is effective for reducing exposure of the heart, left coronary artery (LAD) and both lungs in right breast radiotherapy. We have analyzed 10 consecutive patients with right-sided breast cancer (BC), simulated during free breathing (FB) and in DIBH modality. For all patients we contoured breast PTV and organs at risk (right and left lungs, heart, LAD) on both CT scans (FB and DIBH). Finally, 5 patients were treated with IMRT and 5 with VMAT techniques. All patients were able to end the treatments in DIBH modalities regardless of the longer treatment time in comparison to FB. The maximum and mean dose to the heart are lower in the DIBH modality. The mean values of the heart mean dose were 1.76 Gy in DIBH and 2.19 Gy in FB. The mean heart maximum dose in DIBH and FB were, respectively, 9.3 Gy and 11 Gy. Likewise, the maximum dose to the LAD is lower in DIBH 2.57 Gy versus 3.56 Gy in FB. Noteworthy, 3 patients with hepatomegaly treated with the DIBH technique showed a higher ipsilateral lung dose than FB, but a decrease of liver dose. We report that the use of DIBH for right-sided BC allows the dose to the heart, LAD and to the liver to be reduced in case of hepatomegaly. This technique is well tolerated by patients, when adequately trained, and could be considered effective even in right sided BC.

Anatomy-based prediction method for determining ipsilateral lung doses in postoperative breast radiation therapy assisted by diagnostic computed tomography images.

This study aimed to investigate whether ipsilateral lung doses (ILDs) could be predicted by anatomical indexes measured using diagnostic computed tomography (CT) prior to the planning stage of breast radiation therapy (RT). The thoracic diameters and the length of lines drawn manually were measured on diagnostic CT images. The parameters of interest were the skin maximum lung distance (sMLD), central lung distance (CLD), Haller index (HI), and body mass index (BMI). Lung dose-volume histograms were created with conformal planning, and the lung volumes receiving 5-40 Gy (V5-V40) were calculated. Linear regression models were used to investigate the correlations between the anatomical indexes and dose differences and to estimate the slope and 95% confidence intervals (CIs). A total of 160 patients who had undergone three-dimensional conformal RT after breast-conserving surgery were included. Univariable analysis revealed that the sMLD (p < 0.001), CLD (p < 0.001), HI (p 0.002), and BMI (p < 0.001) were significantly correlated with the V20. However, multivariable analysis revealed that only the sMLD (slope 0.147, p 0.001, 95% CI 0.162-0.306) and CLD (0.157, p 0.005, 0.048-0.266) were strongly correlated with the V20. The p-value for the sMLD was the lowest among the p-values for all indexes, thereby indicating that the sMLD had the best predictive power for ILD. sMLD and CLD are anatomical markers that can be used to predict ILD in whole breast RT. An sMLD > 20.5 mm or a CLD > 24.3 mm positively correlated with a high ILD.

Examination of the dose distribution of volumetric modulated arc radiotherapy using a high-definition multi-leaf collimator for breast cancer patients with irradiated regional lymph nodes.

A high-definition multi-leaf collimator (HD-MLC) with 5- and 10-mm fine MLCs is useful for radiotherapy. However, it is difficult to irradiate the mammary gland and supraclavicular region using a HD-MLC because of the narrow field of volumetric modulated arc radiotherapy (VMAT). Therefore, we aimed to evaluate the dose distribution of the VMAT dose using a HD-MLC in 15 patients with left breast cancer undergoing postoperative irradiation of breast and regional lymph nodes, including the internal mammary node. The following four plans were generated three-arc VMAT using HD-MLC (HD-VMAT), two tangential arcs and one-arc VMAT using HD-MLC (tHD-VMAT), three-dimensional conformal radiotherapy (3DCRT) using HD-MLC, and two-arc VMAT using the Millennium 120-leaf MLC (M-VMAT). We assessed the doses to the target volume and organs at risk. The target dose distributions were higher for HD-VMAT than 3DCRT. There were no significant differences in the heart mean dose (D In cases of the mammary gland and regional lymph node irradiation, including the internal mammary node in patients with left breast cancer, HD-VMAT was not inferior to M-VMAT and provided a better dose distribution to the target volume and organs at risk compared with 3DCRT and tHD-VMAT.

Intraoperative radiation therapy for early-stage breast cancer a single-institution experience.

To assess outcomes and toxicity after low-energy intraoperative radiotherapy (IORT) for early-stage breast cancer (ESBC). We reviewed patients with unilateral ESBC treated with breast-conserving surgery and 50-kV IORT at our institution. Patients were prescribed 20 Gy to the surface of the spherical applicator, fitted to the surgical cavity during surgery. Patients who did not meet institutional guidelines for IORT alone on final pathology were recommended adjuvant treatment, including additional surgery andor external-beam radiation therapy (EBRT). We analyzed ipsilateral breast tumor recurrence, overall survival, recurrence-free survival and toxicity. Among 201 patients (median follow-up, 5.1 years median age, 67 years), 88% were Her2 negative and ER positive andor PR positive, 98% had invasive ductal carcinoma, 87% had grade 1 or 2, and 95% had clinical T1 disease. Most had pathological stage T1 (93%) N0 (95%) disease. Mean IORT applicator dose at 1-cm depth was 6.3 Gy. Post-IORT treatment included additional surgery, 10% EBRT, 11% adjuvant chemotherapy, 9% and adjuvant hormonal therapy, 74%. Median total EBRT dose was 42.4 (range, 40.05-63) Gy and median dose per fraction was 2.65 Gy. At 5 years, the cumulative incidence of ipsilateral breast tumor recurrence was 2.7%, the overall survival rate was 95% with no breast cancer-related deaths, and the recurrence-free survival rate was 96%. For patients who were deemed unsuitable for postoperative IORT alone and did not receive recommended risk-adapted EBRT, the IBTR rate was 4.7% versus 1.7% (p 0.23) for patients who were either suitable for IORT alone or unsuitable and received adjuvant EBRT. Cosmetic toxicity data was available for 83%, with 7% experiencing grade 3 breast toxicity and no grade 4-5 toxicity. IORT for select patients with ESBC results in acceptable outcomes in regard to ipsilateral breast tumor recurrence and toxicity.

Thyroid function following radiation therapy in breast cancer patients risk of radiation-induced hypothyroidism.

Radiation exposure to the thyroid gland seems unavoidable in breast cancer (BC) patients receiving radiation therapy (RT) to the supraclavicular (SC) region. Hence, this study aimed to evaluate the effects of SC region RT on thyroid function and the prevalence of radiation-induced hypothyroidism (RIHT) in BC patients at regular intervals post-treatment. Twenty-one patients with BC were enrolled in this analytical cross-sectional study by simple and convenient sampling, from March 2019 to March 2020. Thyroid function and the prevalence of RIHT were evaluated and compared by measuring the serum of thyroid-stimulating hormone (TSH) and free thyroxine hormone (fT4) levels before radiation therapy (pre-RT) and 3 and 6 months after radiation therapy (post-RT). The patients underwent 3 dimensional conformal. radiation therapy (3D CRT) of breastchest wall, axillary, and supraclavicular lymph nodes with 50 Gy25 fractions5 weeks. The collected data were analyzed using SPSS software (version 20). Serum levels of TSH increased at 3 and 6 months post-RT, this increase was not statistically significant (p > 0.05). Nevertheless, serum levels of fT4 were significantly elevated at 3 and 6 months post-RT (p < 0.01). A correlation was observed between the follow-up period and the incidence of RIHT, where it was 0% at 3 months and 9.5% at 6 months post-RT. RIHT was not significantly associated with any factors, including patients age, type of surgery, thyroid gland dose, and thyroid gland volume. It seems that SC region RT does not have a significant adverse effect on the thyroid function among BC patients at 3 and 6 months post-treatment. Hence, a long-term follow-up with a larger sample size is suggested.

Integrated scoring approach to assess radiotherapy plan quality for breast cancer treatment.

Proposal of an integrated scoring approach assessing the quality of different treatment techniques in a radiotherapy planning comparison. This scoring method incorporates all dosimetric indices of planning target volumes (PTVs) as well as organs at risk (OARs) and provides a single quantitative measure to select an ideal plan. The radiotherapy planning techniques compared were field-in-field (FinF), intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), hybrid IMRT (H-IMRT), and hybrid VMAT (H-VMAT). These plans were generated for twenty-five locally advanced left-sided breast cancer patients. The PTVs were prescribed a hypofractionation dose of 40.5 Gy in 15 fractions. The integrated score for each planning technique was calculated using the proposed formula. An integrated score value that is close to zero indicates a superior plan. The integrated score that incorporates all dosimetric indices (PTVs and OARs) were 1.37, 1.64, 1.72, 1.18, and 1.24 for FinF, IMRT, VMAT, H-IMRT, and H-VMAT plans, respectively. The proposed integrated scoring approach is scientific to select a better plan and flexible to incorporate the patient-specific clinical demands. This simple tool is useful to quantify the treatment techniques and able to differentiate the acceptable and unacceptable plans.

Physiatrists Attitudes and Knowledge About Cancer Rehabilitation.

Objective We aim to assess the awareness and evaluation pattern among physiatrists regarding cancer rehabilitation and associated barriers to access. Design The present study is a cross-sectional study in the Physical Medicine and Rehabilitation (PMR) Association Annual Meeting in Puerto Rico that used a 10-item questionnaire to summarize physiatrists clinical patterns with their persons diagnosed with cancer (PDWCs). Results Thirty-eight (66.7%) participants answered they received minimal to no education about cancer rehabilitation benefits. Cancer patients represented 10% or less of the weekly patient load for 47 (82.5%) physiatrists surveyed. The most common type of cancer encountered was breast cancer for the management of adverse effects. Twenty-nine (50.9%) physiatrists answered that a multifactorial barrier was the cause for limited services within this population group. All participants agreed that rehabilitation is at least sometimes beneficial for cancer patients, and 54 (94.7%) believed these services are needed. Conclusion Although rehabilitation specialists learn about the benefits of rehabilitation for PDWCs, there continues to be a limited number of PDWCs evaluated, mainly due to poor access, lack of information about cancer rehabilitation, and economic difficulties. Further efforts should be made to emphasize the importance of integrating rehabilitation techniques in the care of PDWCs.

Reverse Abdominoplasty for Reconstruction Following Oncologic Resection of Extensive Breast Disease.

We present two cases of patients with extensive breast disease who underwent a reverse abdominoplasty for closure following resection one of Pagets disease extending beyond the breast borders and another of a locally recurrent triple-negative invasive ductal carcinoma following mastectomy in a patient who previously had an ipsilateral thoracotomy. The reverse abdominoplasty flap is a reconstructive option not readily considered for closure following mastectomy. However, we believe that the reverse abdominoplasty flap should be considered when evaluating patients for anterior chest wall reconstruction because it is a simple and versatile coverage option.

Multi-scale cascaded networks for synthesis of mammogram to decrease intensity distortion and increase model-based perceptual similarity.

Synthetic digital mammogram (SDM) is a 2D image generated from digital breast tomosynthesis (DBT) and used as a substitute for a full-field digital mammogram (FFDM) to reduce the radiation dose for breast cancer screening. The previous deep learning-based method used FFDM images as the ground truth, and trained a single neural network to directly generate SDM images with similar appearances (e.g., intensity distribution, textures) to the FFDM images. However, the FFDM image has a different texture pattern from DBT. The difference in texture pattern might make the training of the neural network unstable and result in high-intensity distortion, which makes it hard to decrease intensity distortion and increase perceptual similarity (e.g., generate similar textures) at the same time. Clinically, radiologists want to have a 2D synthesized image that feels like an FFDM image in vision and preserves local structures such as both mass and microcalcifications (MCs) in DBT because radiologists have been trained on reading FFDM images for a long time, while local structures are important for diagnosis. In this study, we proposed to use a deep convolutional neural network to learn the transformation to generate SDM from DBT. To decrease intensity distortion and increase perceptual similarity, a multi-scale cascaded network (MSCN) is proposed to generate low-frequency structures (e.g., intensity distribution) and high-frequency structures (e.g., textures) separately. The MSCN consist of two cascaded sub-networks the first sub-network is used to predict the low-frequency part of the FFDM image the second sub-network is used to generate a full SDM image with textures similar to the FFDM image based on the prediction of the first sub-network. The mean-squared error (MSE) objective function is used to train the first sub-network, termed low-frequency network, to generate a low-frequency SDM image. The gradient-guided generative adversarial networks objective function is to train the second sub-network, termed high-frequency network, to generate a full SDM image with textures similar to the FFDM image. 1646 cases with FFDM and DBT were retrospectively collected from the Hologic Selenia system for training and validation dataset, and 145 cases with masses or MC clusters were independently collected from the Hologic Selenia system for testing dataset. For comparison, the baseline network has the same architecture as the high-frequency network and directly generates a full SDM image. Compared to the baseline method, the proposed MSCN improves the peak-to-noise ratio from 25.3 to 27.9 dB and improves the structural similarity from 0.703 to 0.724, and significantly increases the perceptual similarity. The proposed method can stabilize the training and generate SDM images with lower intensity distortion and higher perceptual similarity.

Six case reports of NTHL1-associated tumor syndrome further support it as a multi-tumor predisposition syndrome.

NTHL1-associated tumor syndrome (NATS) is an autosomal recessive condition characterized by an increased risk for colorectal polyposis and colorectal cancer (CRC). Only 46 case reports have been previously published. In a retrospective review, we analyzed the clinical histories of six patients found to have NATS after genetic counseling and testing. NATS appears to be associated with an increased risk for colorectal polyposis, CRC, female breast cancer, meningiomas, and endometrial cancer. Although research is limited, prior publications have reported a multi-tumor predisposition for individuals with biallelic pathogenic or likely pathogenic variants in NTHL1. Additional data are necessary to further define the cancer risks so affected individuals can be appropriately managed.

The recent advancements in the early detection of cancer biomarkers by DNAzyme-assisted aptasensors.

Clinical diagnostics rely heavily on the detection and quantification of cancer biomarkers. The rapid detection of cancer-specific biomarkers is of great importance in the early diagnosis of cancers and plays a crucial role in the subsequent treatments. There are several different detection techniques available today for detecting cancer biomarkers. Because of target-related conformational alterations, high stability, and target variety, aptamers have received considerable interest as a biosensing system component. To date, several sensitivity-enhancement strategies have been used with a broad spectrum of nanomaterials and nanoparticles (NPs) to improve the limit and sensitivity of analyte detection in the construction of innovative aptasensors. The present article aims to outline the research developments on the potential of DNAzymes-based aptasensors for cancer biomarker detection.

The therapeutic effect of adipose-derived stem cells on soft tissue injury after radiotherapy and their value for breast reconstruction.

Postmastectomy radiotherapy is considered to be a necessary treatment in the therapy of breast cancer, while it will cause soft tissue damage and complications, which are closely related to the success rate and effectiveness of breast reconstruction. After radiotherapy, cutaneous tissue becomes thin and brittle, and its compliance decreases. Component fat grafting and adipose-derived stem cell therapy are considered to have great potential in treating radiation damage and improving skin compliance after radiotherapy. In this paper, the basic types and pathological mechanisms of skin and soft tissue damage to breast skin caused by radiation therapy are described. The 2015-2021 studies related to stem cell therapy in PubMed were also reviewed. Studies suggest that adipose-derived stem cells exert their biological effects mainly through cargoes carried in extracellular vesicles and soluble secreted factors. Compared to traditional fat graft breast reconstruction, ADSC therapy amplifies the effects of stem cells in it. In order to obtain a more purposeful therapeutic effect, proper stem cell pretreatment may achieve more ideal and safe results. Recent research works about ADSCs and other MSCs mainly focus on curative effects in the acute phase of radiation injury, and there is little research about treatment of chronic phase complications. The efficacy of stem cell therapy on alleviating skin fibrosis and its underlying mechanism require further research.

Preclinical development of carrier-free prodrug nanoparticles for enhanced antitumor therapeutic potential with less toxicity.

Nanomedicine has emerged as a promising strategy for cancer treatment. The most representative nanomedicine used in clinic is PEGylated liposomal doxorubicin DOXIL The carrier-free prodrug nanoparticles (F68-FDOX) are prepared by self-assembly of cathepsin B-specific cleavable peptide (FRRG) and doxorubicin (DOX) conjugates without any additional carrier materials, and further stabilized with Pluronic F68, resulting in high drug loading (> 50%). The precise and concise structure allow mass production with easily controllable quality control (QC), and its lyophilized powder form has a great long-term storage stability at different temperatures (- 4, 37 and 60 °C). With high cathepsin B-specificity, F68-FDOX induce a potent cytotoxicity preferentially in cancer cells, whereas their cytotoxicity is greatly minimized in normal cells with innately low cathepsin B expression. In tumor models, F68-FDOX efficiently accumulates within tumor tissues owing to enhanced permeability and retention (EPR) effect and subsequently release toxic DOX molecules by cathepsin B-specific cleavage mechanism, showing a broad therapeutic spectrum with significant antitumor activity in three types of colon, breast and pancreatic cancers. Finally, the safety of F68-FDOX treatment is investigated after single-multi-dosage into mice, showing greatly minimized DOX-related toxicity, compared to free DOX in normal mice. Collectively, these results provide potential preclinical development process of an alternative approach, new formulation of carrier-free prodrug nanoparticles, for clinical translation of nanomedicines.

EVI1 expression in early-stage breast cancer patients treated with neoadjuvant chemotherapy.

Overexpression of the EVI1 (ecotropic viral integration site 1) oncogene has recently been implicated as a prognostic factor in breast cancer (BC), particularly in triple-negative BC (TNBC). In this study we aimed to investigate frequency and clinical relevance of EVI1 expression in newly diagnosed BC treated with neoadjuvant chemotherapy. EVI1 expression was determined by immunohistochemistry using H-score as a cumulative measurement of protein expression in pretherapeutic biopsies of BC patients treated with anthracyclinetaxane based neoadjuvant chemotherapy within the GeparTrio trial. EVI1 was analyzed as a continuous variable and dichotomized into low or high based on median expression. Endpoints were pathological complete response (pCR), disease-free survival (DFS) and overall survival (OS). Of the 993 tumors analyzed, 882 had available subtype information 50.8% were HR HER2-, 15% HR HER2 , 9.8% HR-HER2 , and 24.5% TNBC. Median EVI1 H-score was 112.16 (range 0.5-291.4). High EVI1 expression was significantly associated with smaller tumor size (p 0.002) but not with BC subtype. Elevated EVI1 levels were not significantly associated with therapy response and survival in the entire cohort or within BC subtypes. However, TNBC patients with high EVI1 showed a trend towards increased pCR rates compared to low group (37.7% vs 27.5%, p 0.114 odds ratio 1.60 (95%CI 0.90-2.85, p 0.110) and numerically better DFS (HR 0.77 95%CI 0.48-1.23, log-rank p 0.271) and OS (HR 0.76 95% 0.44-1.31, log-rank p 0.314) without reaching statistical significance. EVI1 was not associated with response to neoadjuvant therapy or patient survival in the overall cohort. Further analyses are needed to verify our findings especially in the pathological work-up of early-stage HER2-negative BC patients. NCT00544765.

Surgical site infection in reconstructive and aesthetic breast surgery A single center retrospective analysis of the association between healthcare workers and infections.

Reconstructive and aesthetic breast surgeries are frequently performed procedures, and the consequences of a postoperative infection are devastating both for the patient and the healthcare (HC) system. Over the years, there has been heightened interest in the physical and mental well-being of physicians and HC workers. Little is known about the relationship between HC workers and surgical site infections (SSI), and whether HC workers are at an increased risk for SSI. The aim of this study was to investigate whether women working in the HC system have an increased risk for SSI following reconstructive and aesthetic breast surgery. We conducted a retrospective analysis of all patients who underwent aesthetic and reconstructive breast surgery at our institution between the years 2013-2020. Women who were recognized as HC workers were analyzed in a separate group and compared to those who were not. Records of 378 patients were reviewed, of whom 53 (14%) were identified as HC workers. The overall infection rate was 17.4%. HC workers manifested a higher infection rate than the other group (32% vs. 15.1%, p<0.05) and a significantly higher relative risk for SSI (RR 2.12, p<0.01). Women working in the HC system may have an increased risk of developing postoperative infectious complications following aesthetic and reconstructive breast-related surgery. Further research is needed to corroborate these findings and elucidate the causes.

Automated BI-RADS classification of lesions using pyramid triple deep feature generator technique on breast ultrasound images.

Ultrasound (US) is an important imaging modality used to assess breast lesions for malignant features. In the past decade, many machine learning models have been developed for automated discrimination of breast cancer versus normal on US images, but few have classified the images based on the Breast Imaging Reporting and Data System (BI-RADS) classes. This work aimed to develop a model for classifying US breast lesions using a BI-RADS classification framework with a new multi-class US image dataset. We proposed a deep model that combined a novel pyramid triple deep feature generator (PTDFG) with transfer learning based on three pre-trained networks for creating deep features. Bilinear interpolation was applied to decompose the input image into four images of successively smaller dimensions, constituting a four-level pyramid for downstream feature generation with the pre-trained networks. Neighborhood component analysis was applied to the generated features to select each networks 1,000 most informative features, which were fed to support vector machine classifier for automated classification using a ten-fold cross-validation strategy. Our proposed model was validated using a new US image dataset containing 1,038 images divided into eight BI-RADS classes and histopathological results. We defined three classification schemes Case 1 involved the classification of all images into eight categories Case 2, classification of breast US images into five BI-RADS classes and Case 3, classification of BI-RADS 4 lesions into benign versus malignant classes. Our PTDFG-based transfer learning model attained accuracy rates of 79.29%, 80.42%, and 88.67% for Case 1, Case 2, and Case 3, respectively.

Human Pharmacokinetics of LYS006, an Oral Leukotriene A4 Hydrolase Inhibitor Displaying Target-Mediated Drug Disposition.

LYS006 is a potent leukotriene A4 hydrolase inhibitor currently in clinical development for long-term treatment of various neutrophil-driven inflammatory conditions. Here, we present pharmacokinetics from the first-in-human study with complementary metabolism and transporter profiling data. The randomized first-in-human study included nine cohorts receiving 5-2100 mg of LYS006 or placebo, a crossover food-effect part, and a multiple-dose part consisting of two fasted (5 mg and 15 mg once daily) and three fed cohorts (20-80 mg twice a day) of LYS006 or placebo. LYS006 and metabolites were assessed in plasma and urine, and transporters involved in LYS006 disposition were analyzed in vitro. Systemic plasma exposure increased with dose steady-state exposure was dose proportional up to 40 mg twice a day. Steady state was achieved after ∼3 days, with mean accumulation of 2.1-fold for 5 mg once daily and ≤1.4-fold for all higher doses. Despite limited accumulation, a long terminal half-life (T

A first-in-class clinical G-quadruplex-targeting drug. The bench-to-bedside translation of the fluoroquinolone QQ58 to CX-5461 (Pidnarulex).

CX-3543 (Quarfloxin) and CX-5461 (Pidnarulex) were originally derived from a group of fluoroquinolones that were shown to have dual topoisomerase II (Top2) and G-quadruplex (G4) interactions, and QQ58 was the starting structure for their design. Quarfloxin was initially shown to inhibit c-MYC mRNA expression. Studies at Cylene Pharmaceuticals showed that the primary mechanism of action of Quarfloxin is due to displacement of nucleolin from quadruplexes on the non-template strand of rDNA, causing rapid redistribution of nucleolin from nucleoli, inhibition of rRNA synthesis, and apoptotic death in cancer cells. At Cylene a follow-up compound to Quarfloxin, named Pidnarulex (CX-5461), was optimized for targeting RNA Pol 1. Significantly, in more recent work published in Proc Natl Acad Sci USA and Cell in 2020 and in eLIFE and Nat Comm in 2021, it has been shown that the real molecular target for Pidnarulex is Top2 at transcribed regions containing G4s, rather than RNA Pol 1. These results support the original design strategy published in Mol Cancer Ther in 2001, which was to rationally design a G4-targeting drug (QQ58) starting from a fluoroquinolone duplex-targeting Top2 poison (A-62176) that had good drug-like properties. A very important breakthrough was realized when homologous recombination (HR) was found to be important in the repair of DNA damage caused by G4-interactive compounds, suggesting that a synthetic lethal approach might be useful in identifying cancer patients sensitive to these agents. Through use of an unbiased screen, this mechanistic insight was shown to directly apply to Cylene compounds, which were found to induce DNA damage and to be dependent on BRCA12-mediated HR and the DNA-PK-mediated nonhomologous end-joining (NHEJ) pathway for damage repair. To evaluate how this mechanistic insight involving a synthetic lethal approach might be applied clinically, a recent Canadian Phase I clinical trial with Pidnarulex in breast and ovarian cancer patients with known BRCA12 germline mutations was carried out. Because of the G4 stabilizer function of Pidnarulex, patient populations that responded well to this compound were identified they are cancer patients with BRCA12 deficiency or deficiency in other DNA damage response pathways. Clinically observed resistance to Pidnarulex resulted from reversion to WT BRCA2 and PALB2 (partner and localizer of BRCA2, because it partners with another gene, called BRCA2), thus providing strong evidence for the underlying synthetic lethal hypothesis proposed for G4-targeting compounds that cause DNA damage.

Adaptive resistance is not responsible for long-term drug resistance in a cellular model of triple negative breast cancer.

Resistance to cancer therapeutics represents a leading cause of mortality and is particularly important in cancers, such as triple negative breast cancer, for which no targeted therapy is available, as these are only treated with traditional chemotherapeutics. Cancer, as well as bacterial, drug resistance can be intrinsic, acquired or adaptive. Adaptive cancer drug resistance is gaining attention as a mechanism for the generation of long-term drug resistance as is the case with bacterial antibiotic resistance. We have used a cellular model of triple negative breast cancer (CAL51) and its drug resistance derivative (CALDOX) to gain insight into genome-wide expression changes associated with long-term doxorubicin (a widely used anthracycline for cancer treatment) resistance and doxorubicin-induced stress. Previous work indicates that both naïve and resistance cells have a functional p53-p21 axis controlling cell cycle at G1, although this is not a driver for drug resistance, but down-regulation of TOP2A (topoisomerase IIα). As expected, CALDOX cells have a signature characterized, in addition to down-regulation of TOP2A, by genes and pathways associated with drug resistance, metastasis and stemness. Both CAL51 and CALDOX stress signatures share 12 common genes (TRIM22, FAS, SPATA18, SULF2, CDKN1A, GDF15, MYO6, CXCL5, CROT, EPPK1, ZMAT3 and CD44), with roles in the above-mentioned pathways, indicating that these cells have similar functional responses to doxorubicin relaying on the p53 control of apoptosis. Eight genes are shared by both drug stress signatures (in CAL51 and CALDOX cells) and CALDOX resistant cells (FAS, SULF2, CDKN1A, CXCL5, CD44, SPATA18, TRIM22 and CROT), many of them targets of p53. This corroborates experimental data indicating that CALDOX cells, even in the absence of drug, have activated, at least partially, the p53-p21 axis and DNA damage response. Although this eight-gene signature might be an indicator of adaptive resistance, as this transient phenomenon due to short-term stress may not revert to its original state upon withdrawal of the stressor, previous experimental data indicates that the p53-p21 axis is not responsible for doxorubicin resistance. Importantly, TOP2A is not responsive to doxorubicin treatment and thus absent in both drug stress signatures. This indicates that during the generation of doxorubicin resistance, cells acquire genetic changes likely to be random, leading to down regulation of TOP2A, but selected during the generation of cells due to the presence of drug in the culture medium. This poses a considerable constraint for the development of strategies aimed at avoiding the emergence of drug resistance in the clinic.

Adaptation of the gut holobiont to malnutrition during mouse pregnancy depends on the type of nutritional adversity.

Malnutrition can influence maternal physiology and programme offspring development. Yet, in pregnancy, little is known about how dietary challenges that influence maternal phenotype affect gut structure and function. Emerging evidence suggests that interactions between the environment, multidrug resistance (MDR) transporters and microbes may influence maternal adaptation to pregnancy and regulate fetoplacental development. We hypothesized that the gut holobiont (host and microbes) during pregnancy adapts differently to suboptimal maternal diets, evidenced by changes in the gut microenvironment, morphology, and expression of key protective MDR transporters during pregnancy. Mice were fed a control diet (CON) during pregnancy, or undernourished (UN) by 30% of control intake from gestational day (GD) 5.5-18.5, or fed 60% high fat diet (HF) for 8 weeks before and during pregnancy. At GD18.5, maternal small intestinal (SI) architecture (HE), proliferation (Ki67), P-glycoprotein (P-gp - encoded by Abcb1ab) and breast cancer resistance protein (BCRPAbcg2) MDR transporter expression and levels of pro-inflammatory biomarkers were assessed. Circulating inflammatory biomarkers and maternal caecal microbiome composition (G3 PhyloChip

Computational modeling implicates protein scaffolding in p38 regulation of Akt.

Cells process environmental cues by activating intracellular signaling pathways with numerous interconnections and opportunities for cross-regulation. We employed a systems biology approach to investigate intersections of kinase p38, a context-dependent tumor suppressor or promoter, with Akt and ERK, two kinases known to promote cell survival, proliferation, and drug resistance in cancer. Using live, single cell microscopy, multiplexed fluorescent reporters of p38, Akt, and ERK activities, and a custom automated image-processing pipeline, we detected marked heterogeneity of signaling outputs in breast cancer cells stimulated with chemokine CXCL12 or epidermal growth factor (EGF). Basal activity of p38 correlated inversely with amplitude of Akt and ERK activation in response to either ligand. Remarkably, small molecule inhibitors of p38 immediately decreased basal activities of Akt and ERK but increased the proportion of cells with high amplitude ligand-induced activation of Akt signaling. To identify mechanisms underlying cross-talk of p38 with Akt signaling, we developed a computational model incorporating subcellular compartmentalization of signaling molecules by scaffold proteins. Dynamics of this model revealed that subcellular scaffolding of Akt accounted for observed regulation by p38. The model also predicted that differences in the amount of scaffold protein in a subcellular compartment captured the observed single cell heterogeneity in signaling. Finally, our model predicted that reduction in kinase signaling can be accomplished by both scaffolding and direct kinase inhibition. However, scaffolding inhibition can potentiate future kinase activity by redistribution of pathway components, potentially amplifying oncogenic signaling. These studies reveal how computational modeling can decipher mechanisms of cross-talk between the p38 and Akt signaling pathways and point to scaffold proteins as central regulators of signaling dynamics and amplitude.

Adhesion of LHRHEphA2 to human Triple Negative Breast Cancer tissues.

The adhesive interactions between molecular recognition units (such as specific peptides and antibodies) and antigens or other receptors on the surfaces of tumors are of great value in the design of targeted nanoparticles and drugs for the detection and treatment of specific cancers. In this paper, we present the results of a combined experimental and theoretical study of the adhesion between Luteinizing Hormone Releasing Hormone (LHRH)Epherin type A2 (EphA2)-AFM coated tips and LHRHEphA2 receptors that are overexpressed on the surfaces of human Triple Negative Breast Cancer (TNBC) tissues of different histological grades. Following a histochemical and immuno-histological study of human tissue extracts, the receptor overexpression, and their distributions are characterized using Immunohistochemistry (IHC), Immunofluorescence (IF), and a combination of fluorescence microscopy and confocal microscopy. The adhesion forces between LHRH or EphA2 and human TNBC breast tissues are measured using force microscopy techniques that account for the potential effects of capillary forces due to the presence of water vapor. The corresponding adhesion energies are also determined using adhesion theory. The pull off forces and adhesion energies associated with higher grades of TNBC are shown to be greater than those associated with normalnon-tumorigenic human breast tissues, which were studied as controls. The observed increase in adhesion forces and adhesion energies are also correlated with the increasing incidence of LHRHEphA2 receptors at higher grades of TNBC. The implications of the results are discussed for the development of targeted nanostructures for the detection and treatment of TNBC.

Mixed computational-experimental study to reveal the anti-metastasis and anti-angiogenesis effects of Astragalin in human breast cancer.

Breast cancer is the most aggressive malignant tumor with high morbidity and mortality. Astragalin, a flavonoid widely found in a variety of edible and medicinal plants, is recorded to possess multiple biological and pharmacological activities. However, its effect of anti-breast cancer has been unknown. Computational pharmacology was employed to explore the potential mechanism of anti-metastasis and anti-angiogenesis effects of Astragalin on breast cancer. The targets of Astragalin were obtained from TCMSP, Swiss Target Prediction, SEA, BATMAN-TCM, ChemMapper and STITCH databases, and targets of breast cancer were got from OMIM, GeneCards, and DisGeNET databases. Protein-protein interaction network (PPI), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to elucidate the interactions of these two groups of targets. Moreover, the anti-metastasis and anti-angiogenesis effects of Astragalin were validated by in vitro and in vivo experiments using wound healing assay, transwell migration and invasion assay, gelatin zymography assay, tube formation assay, and chick embryo chorioallantoic membrane model. Computational pharmacology analysis indicated that the effects of Astragalin against breast cancer were mainly related to the regulation of the cell movement, migration, and angiogenesis, and taking AKT, ZEB1, VEGF, and MMP9 as the promising targets. Further experimental pharmacology indicated that Astragalin exerted anti-metastasis and anti-angiogenesis activities on breast cancer, and verified AKT, ZEB1, VEGF, and MMP9 as the key targets. Astragalin suppresses the metastasis and angiogenesis of breast cancer, and AKT, ZEB1, VEGF, and MMP9 are the promising targets for Astragalin against breast cancer. Thus, Astragalin is a potential therapeutic agent for breast cancer.

Mammogram classification based on a novel convolutional neural network with efficient channel attention.

Early accurate mammography screening and diagnosis can reduce the mortality of breast cancer. Although CNN-based breast cancer computer-aided diagnosis (CAD) systems have achieved significant results in recent years, precise diagnosis of lesions in mammogram remains a challenge due to low signal-to-noise ratio (SNR) and physiological characteristics. Many researchers achieved excellent performance in detecting mammographic images by inputting region of interest (ROI) annotations while ROI annotations require a great quantity of manual labor, time and resources. We propose a two-stage method that combines images preprocessing and model optimization to address the aforementioned challenges. Firstly, we propose the breast database preprocess (BDP) method to preprocess INbreast then we get INbreast

Expression analysis of autophagy-related long non-coding RNAs in Iranian patients with breast cancer.

Autophagy has an established role in the development and progression of breast cancer. Recent studies have shown functional links between long non-coding RNAs (lncRNAs) and autophagy process. LINC01963, AL132989.1, RAB11B-AS1, PLBD1-AS1, AL139158.2, LOC105376805 (BX284668.5) and HERPUD2-AS1 (AC018647.2) are among autophagy related lncRNAs. In the current study, we compared expression of these seven lncRNAs between breast cancer samples and their paired non-cancerous tissues. RAB11B-AS1, HERPUD2-AS1 and PLBD1-AS1 were up-regulated in tumor samples compared with non-tumoral samples (Expression ratios (95% CI) 2.56 (1.22-5.36), 2.13 (1.02-4.43) and 21.3 (10.36-43.89), respectively). ROC curve analysis indicated that PLBD1-AS1, RAB11B-AS1 and HERPUD2-AS1 had AUC values of 0.78, 0.61 and 0.6 for separation of breast cancer tissues from controls. Expression level of AL132989.1 in tumor tissues was associated with tubule formation (P value0.02) in a way that tumor tissues with tubular formation score 1 had lower expression of AL132989.1. There was also a significant difference between expression levels of AL139158.2.1 among tumor tissues with different clinical stages (P value0.02). Tumor tissues with higher clinical stages showed decreased expression of AL139158.2.1. In addition, there was also a significant difference between expression level of HERPUD2-AS1 in tumor tissues with different histological tumor grade and tubule formation (P value0.03 and 0.003, respectively). Tumor tissues with higher histological tumor grade and higher tubule formation score showed higher expression of HERPUD2-AS1. Taken together, this study provides evidence for contribution of a number of recently identified autophagy-related lncRNAs in the pathogenesis of breast cancer.

Inhibition of alanine-serine-cysteine transporter 2-mediated auto-enhanced photodynamic cancer therapy of co-nanoassembly between V-9302 and photosensitizer.

The efficiency of reactive oxygen species (ROS)-based photodynamic therapy (PDT) is far from satisfactory, because cancer cells can adapt to PDT by upregulating glutathione (GSH) levels. The GSH levels in tumor cells are determined based on glutamine availability via alanine-serine-cysteine transporter 2 (ASCT2)-mediated entry into cells. Herein, we develop co-assembled nanoparticles (PPaV-9302 NPs) of the photosensitizer pyropheophorbide a (PPa) and V-9302 (a known inhibitor of ASCT2) in a 11 M ratio using a one-step precipitation method to auto-enhance photodynamic therapy. The computational simulations revealed that PPa and V-9302 could self-assemble through different driving forces, such as π-π stacking, hydrophobic interactions, and ionic bonds. Such PPaV-9302 NPs could disrupt the intracellular redox homeostasis due to enhanced ROS production via PPa-induced PDT and reduced GSH synthesis via inhibition of the ASCT2-mediated glutamine flux by V-9302. The in vivo assays reveal that PPaV-9302 NPs could increase the drug accumulation in tumor sites and suppress tumor growth in BALBc mice bearing mouse breast carcinoma (4 T1) tumor. Our findings provide a new paradigm for the rational design of the PDT-based combinational cancer therapy.

Predictors of behavioral cancer risk factors and preventive behaviors among Nebraskans.

The overall incidence rate of cancer in Nebraska is higher than the national average with cancer being the second leading cause of death in the state. Interventions are required to reduce the cancer burden however, further research is first needed to identify behavioral cancer risk factors and preventive behaviors among Nebraskans that can be targeted. A statewide cross-sectional survey of Nebraskans aged 19 and older was conducted in 2019 using an address-based sampling method (n 1640). Multivariable logistic regression was used to examine factors associated with being up-to-date on cancer screening and with behavioral cancer risk factors and preventive behaviors. 93.42% of Nebraskans did not meet the daily recommended consumption of fruits and vegetables, and 71.51% did not meet weekly physical activity guidelines. The proportion of adults up to date on cancer screening was 64.57% for breast, 68.83% for cervical, 69.01% for colorectal, and 24.07% for skin cancers. Individuals 65-74 (OR 3.40, 95% CI 1.52-7.62) and 75 or older (OR 3.30, 95% CI 1.35-8.07) were more likely to be current with their colorectal cancer screening compared to ages 50-64. Hispanics were less likely to be current with mammograms (OR 0.06, 95% CI 0.01-0.71) and ever screened for cervical cancer (OR0.13, 95% CI 0.02-0.94) compared to Non-Hispanic Whites. Disparities in cancer screening and risk and preventive behaviors exist in Nebraska. The study highlights a need for continuing efforts to improve preventive cancer behaviors for the entire population as well as some high-risk populations in Nebraska.

Breast cancer diagnosis in Inner-City African American and Hispanic women The importance of early screening.

To evaluate the diagnosis of breast cancer in inner-city African-American and Hispanic women under age 50 to support the importance of screening in this population. This retrospective chart review included women newly diagnosed with breast cancer from 112015 to 112019 in a city hospital mainly serving minority patients. Chi-square and Fishers exact tests were used for analysis. In this cohort of 108 newly diagnosed African-American (63%) and Hispanic (31%) women, 60108 (56%) presented with a site of palpable concern for diagnostic workup, and the remaining were diagnosed via asymptomatic screening. Women ages 30-49 were significantly more likely to present with a site of palpable concern when compared to women ages 50-69 (68% vs. 44%, p 0.045). Additionally, women ages 30-49 were more likely to have triple-negative breast cancer (TNBC) than women ages 50-69 (20% vs. 10%, p 0.222). However, women ages 30-49 were less likely to have prior mammogram than women ages 50-69 (24% vs. 46%, p 0.062). African-American and Hispanic women ages 30-49 were more likely to present with a site of palpable concern and TNBC than those ages 50-69. However, these young minority women ages 30-49 were less likely to have prior screening mammograms when compared to those ages 50-69. Our data highlights the importance of starting screening mammography no later than age 40 in African-American and Hispanic women. In addition, these women should have risk assessment for breast cancer no later than age 30 and be screened appropriately.