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36,230,767 | Prognostic and Predictive Significance of Stromal Tumor-Infiltrating Lymphocytes (sTILs) in ER-PositiveHER2-Negative Postmenopausal Breast Cancer Patients. | The clinical impact of tumor-infiltrating lymphocytes (TILs) is less known for breast cancer patients with the estrogen receptor-positive (ER)human epidermal growth factor receptor-negative (HER-) subtype. Here, we explored the prognostic and predictive value of TILs regarding distant recurrence-free interval (DRFI) and breast cancer-specific survival (BCSS) in 763 postmenopausal patients randomized to receive tamoxifen vs. no systemic treatment. TILs were assessed in whole section tumor samples stained with HE and divided into low (lt10%), intermediate (10-39%), or high (≥40%). High TILs were associated with poor prognostic variables and good prognoses for all patients, but not within the ERHER2- group. Within the ERHER2- group, high gene expression of CD19 and PD-L1 and high IMMUNE1 score indicated good prognosis in multivariable analysis while high CD8 and CD19 gene expression and high IMMUNE1 score were associated with less tamoxifen benefit. These results indicate that within the ERHER2- subtype there could be subsets of patients where expression of specific TIL markers might be used to reveal candidates for immune therapy interventions upon failure of the endocrine therapy. |
36,230,762 | Long-Term Breast Cancer Outcomes of Pregnancy-Associated Breast Cancer (PABC) in a Prospective Cohort. | Given that peak age of breast cancer (BC) is younger in Asians than in Western populations, relatively higher prevalence of pregnancy-associated breast cancer (PABC) has been reported. This study aimed to analyze the characteristics and clinical outcomes of PABC in Korea. We defined PABC as BC diagnosed during pregnancy or in the first postpartum year. We compared the clinicopathological characteristics and BC outcomes between patients with PABC and non-PABC patients in the prospective YBC cohort from Samsung Medical Center. In total, 1492 patients were initially enrolled, and 1364 patients were included, of which 93 had PABC (6.8%). The median age of patients with PABC was 34 years. Hormone receptor expression was lower (64.6% vs 74.6%) and frequency of HER2 overexpression was higher (26.9% vs 17.6%) in patients with PABC than in non-PABC patients. The 5-year overall survival (OS) rates were 83.2% and 93.4% in patients with PABC and non-PABC patients, respectively ( Compared to non-PABC patients, patients with PABC had poorer OS and DFS in this prospective cohort. Exploratory biomarker analysis for PABC is warranted. |
36,230,758 | The Impact of the Hippo Pathway and Cell Metabolism on Pathological Complete Response in Locally Advanced Her2 Breast Cancer The TRISKELE Multicenter Prospective Study. | The Hippo pathway and its two key effectors, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), are consistently altered in breast cancer. Pivotal regulators of cell metabolism such as the AMP-activated protein kinase (AMPK), Stearoyl-CoA-desaturase 1 (SCD1), and HMG-CoA reductase (HMGCR) are relevant modulators of TAZYAP activity. In this prospective study, we measured the tumor expression of TAZ, YAP, AMPK, SCD1, and HMGCR by immunohistochemistry in 65 Her2 breast cancer patients who underwent trastuzumab-based neoadjuvant treatment. The aim of the study was to assess the impact of the immunohistochemical expression of the Hippo pathway transducers and cell metabolism regulators on pathological complete response. Low expression of cytoplasmic TAZ, both alone and in the context of a composite signature identified by machine learning including also low nuclear levels of YAP and HMGCR and high cytoplasmic levels of SCD1, was a predictor of residual disease in the univariate logistic regression. This finding was not confirmed in the multivariate model including estrogen receptor gt 70% and body mass index gt 20. However, our findings were concordant with overall survival data from the TCGA cohort. Our results, possibly affected by the relatively small sample size of this study population, deserve further investigation in adequately sized, ad hoc prospective studies. |
36,230,754 | Effectiveness of Organized Mammography Screening for Different Breast Cancer Molecular Subtypes. | Screening program effectiveness is generally evaluated for breast cancer (BC) as one disease and without considering the regularity of participation, while this might have an impact on detection rate. To evaluate the short-term effectiveness of a mammography screening program for the major molecular subtypes of invasive BC. All women who participated in the screening program and were diagnosed with screen-detected or interval BC in Flanders were included in the study (2008-2018). Molecular subtypes considered were luminal and luminal-HER2-positive, human epidermal growth factor receptor 2-positive, and triple-negative BC (TNBC). The relationship between the BC stage at diagnosis (early (I-II) versus advanced (III-IV)) and the method of detection (screen-detected or interval) and the relationship between the method of detection and participation regularity (regular versus irregular) were evaluated by multi-variable logistic regression models. All models were performed for each molecular subtype and adjusted for age. Among the 12,318 included women, BC of luminal and luminal-HER2-positive subtypes accounted for 70.9% and 11.3%, respectively. Screen-detected BC was more likely to be diagnosed at early stages than interval BC with varied effect sizes for luminal, luminal-HER2-positive, and TNBC with OR2.82 (95% CI 2.45-3.25), OR2.39 (95% CI 1.77-3.24), and OR2.29 (95% CI 1.34-4.05), respectively. Regular participation was related to a higher likelihood of screening detection than irregular participation for luminal, luminal-HER2-positive, and TNBC with OR1.21 (95% CI 1.09-1.34), OR 1.79 (95% CI 1.38-2.33), and OR 1.62 (95% CI 1.10-2.41), respectively. Regular screening as compared to irregular screening is effective for all breast cancers except for the HER2 subtype. |
36,230,752 | Association of CD206 Protein Expression with Immune Infiltration and Prognosis in Patients with Triple-Negative Breast Cancer. | Triple-negative breast cancers (TNBCs) have a worse prognosis, but might respond to immunotherapies. Macrophages are plastic cells that can adopt various phenotypes and functions. Although they are a major immune population in TNBCs, the relationship between tumor-associated macrophages (TAMs) and TNBC progression has been rarely explored, with controversial results. We evaluated the prognostic impact of TAMs, quantified by immunohistochemistry with anti-CD68, -IRF8, -CD163, and -CD206 antibodies, in a well-described cohort of 285 patients with non-metastatic TNBC. CD68 ( These data suggest that CD206 expression defines a TAM subpopulation potentially associated with favorable outcomes in patients with TNBC. CD206 expression might identify an immune TNBC subgroup with specific therapeutic options. |
36,230,739 | Novel Methods of Targeting IL-1 Signalling for the Treatment of Breast Cancer Bone Metastasis. | Breast cancer bone metastasis is currently incurable. Evidence suggests that inhibiting IL-1 signalling with the IL1R antagonist, Anakinra, or the IL1β antibody, Canakinumab, prevents metastasis and almost eliminates breast cancer growth in the bone. However, these drugs increase primary tumour growth. We, therefore, investigated whether targeting other members of the IL-1 pathway (Caspase-1, IL1β or IRAK1) could reduce bone metastases without increasing tumour growth outside of the bone. Inhibition of IL-1 via MLX01 (IL1β secretion inhibitor), VRT043198VX765 (Caspase-1 inhibitor), Pacritinib (IRAK1 inhibitor) or Anakinra (IL1R antagonist) on tumour cell viability, migration and invasion were assessed in mouse mammary E0771 and Py8119 cells in vitro and on primary tumour growth, spontaneous metastasis and metastatic outgrowth in vivo. In vitro, Inhibition of IL-1 signalling by MLX01, VRT043198 and Anakinra reduced migration of E0771 and Py8119 cells and reversed tumour-derived IL1β induced-increased invasion and migration towards bone cells. In vivo, VX765 and Anakinra significantly reduced spontaneous metastasis and metastatic outgrowth in the bone, whereas MLX01 reduced primary tumour growth and bone metastasis. Pacritinib had no effect on metastasis in vitro or in vivo. Targeting IL-1 signalling with small molecule inhibitors may provide a new therapeutic strategy for breast cancer bone metastasis. |
36,230,738 | SIPA1 Regulates LINC01615 to Promote Metastasis in Triple-Negative Breast Cancer. | Long non-coding RNAs (lncRNAs) are reported to play an important regulatory effect in carcinogenesis and malignancy. We found by high-throughput sequencing that LINC01615 is upregulated in breast cancer patients and reduces patients overall survival. In vivo and in vitro experiments, we clarified that overexpression of LINC01615 can promote breast cancer cell metastasis ability. The expression of LINC01615 is regulated by the transcriptional activator SIPA1, thereby promoting carcinogenesis in breast cancer cells. Our research clarified that LINC01615 can act as an oncogenic factor in promoting the development of breast cancer. |
36,230,729 | Novel Small Multilamellar Liposomes Containing Large Quantities of Peptide Nucleic Acid Selectively Kill Breast Cancer Cells. | Peptide nucleic acid (PNA) may be used in various biomedical applications however, these are currently limited, due to its low solubility in aqueous solutions. In this study, a methodology to overcome this limitation is demonstrated, as well as the effect of PNA on cell viability. We show that extruding a mixture of natural phospholipids and short (6-22 bases), cytosine-rich PNA through a 100 nm pore size membrane under mild acidic conditions resulted in the formation of small (60-90 nm in diameter) multilamellar vesicles (SMVs) comprising several (3-5) concentric lipid membranes. The PNA molecules, being positively charged under acidic conditions (due to protonation of cytosine bases in the sequence), bind electrostatically to negatively charged phospholipid membranes. The large membrane surface area allowed the encapsulation of thousands of PNA molecules in the vesicle. SMVs were conjugated with the designed ankyrin repeat protein (DARPin9-29), which interacts with human epidermal growth factor receptor 2 (HER2), overexpressed in human breast cancer. The conjugate was shown to enter HER2-overexpressing cells by receptor-mediated endocytosis. PNA molecules, released from lysosomes, aggregate in the cytoplasm into micron-sized particles, which interfere with normal cell functioning, causing cell death. The ability of DARPin-functionalized SMVs to specifically deliver large quantities of PNA to cancer cells opens a new promising avenue for cancer therapy. |
36,230,728 | Emergence of | The |
36,230,723 | External Validation of a Mammography-Derived AI-Based Risk Model in a U.S. Breast Cancer Screening Cohort of White and Black Women. | Despite the demonstrated potential of artificial intelligence (AI) in breast cancer risk assessment for personalizing screening recommendations, further validation is required regarding AI model bias and generalizability. We performed external validation on a U.S. screening cohort of a mammography-derived AI breast cancer risk model originally developed for European screening cohorts. We retrospectively identified 176 breast cancers with exams 3 months to 2 years prior to cancer diagnosis and a random sample of 4963 controls from women with at least one-year negative follow-up. A risk score for each woman was calculated via the AI risk model. Age-adjusted areas under the ROC curves (AUCs) were estimated for the entire cohort and separately for White and Black women. The Gail 5-year risk model was also evaluated for comparison. The overall AUC was 0.68 (95% CIs 0.64-0.72) for all women, 0.67 (0.61-0.72) for White women, and 0.70 (0.65-0.76) for Black women. The AI risk model significantly outperformed the Gail risk model for all women |
36,230,721 | Heterogeneity and Functions of Tumor-Infiltrating Antibody Secreting Cells Lessons from Breast, Ovarian, and Other Solid Cancers. | Neglected for a long time in cancer, B cells and ASCs have recently emerged as critical actors in the tumor microenvironment, with important roles in shaping the antitumor immune response. ASCs indeed exert a major influence on tumor growth, patient survival, and response to therapies. The mechanisms underlying their pro- vs. anti-tumor roles are beginning to be elucidated, revealing the contributions of their secreted antibodies as well as of their emerging noncanonical functions. Here, concentrating mostly on ovarian and breast cancers, we summarize the current knowledge on the heterogeneity of tumor-infiltrating ASCs, we discuss their possible local or systemic origin in relation to their immunoglobulin repertoire, and we review the different mechanisms by which antibody (Ab) subclasses and isoforms differentially impact tumor cells and anti-tumor immunity. We also discuss the emerging roles of cytokines and other immune modulators produced by ASCs in cancer. Finally, we propose strategies to manipulate the tumor ASC compartment to improve cancer therapies. |
36,230,716 | AKT Regulation of ORAI1-Mediated Calcium Influx in Breast Cancer Cells. | Although breast cancer cells often exhibit both abnormal AKT signaling and calcium signaling, the association between these two pathways is unclear. Using a combination of pharmacological tools, siRNA and CRISPRCas9 gene silencing techniques, we investigated the association between PTEN, AKT phosphorylation and calcium signaling in a basal breast cancer cell line. We found that siRNA-mediated PTEN silencing promotes AKT phosphorylation and calcium influx in MDA-MB-231 cells. This increase in AKT phosphorylation and calcium influx was phenocopied by the pharmacological AKT activator, SC79. The increased calcium influx associated with SC79 is inhibited by silencing AKT2, but not AKT1. This increase in calcium influx is suppressed when the store-operated calcium channel, ORAI1 is silenced. The results from this study open a novel avenue for therapeutic targeting of cancer cells with increased AKT activation. Given the association between ORAI1 and breast cancer, ORAI1 is a possible therapeutic target in cancers with abnormal AKT signaling. |
36,230,711 | Differential Intracellular Protein Distribution in Cancer and Normal Cells-Beta-Catenin and CapG in Gynecologic Malignancies. | It is well-established that cancer and normal cells can be differentiated based on the altered |
36,230,696 | Oral Contraceptive Use and Breast Cancer Risk for BRCA1 and BRCA2 Mutation Carriers Systematic Review and Meta-Analysis of Case-Control Studies. | Oral contraceptive use is one of the major modifiable risk factors for breast cancer. To investigate the effect of oral contraceptive taking on breast cancer risk by BRCA 1 and BRCA 2 mutation status, we conducted a systematic review and meta-analysis of case-controlled studies. Therefore, English language articles were retrieved by searching MEDLINE (PubMed), EMBASE and the Cochrane Library up to August 2021. Data were pooled from none case-control studies, comprising a total of 33,162 subjects, including 23,453 who had never used oral contraceptives. Overall meta-analysis indicated a statistically insignificant risk reduction OR 0.86, 95% CI 0.70 to 1.06, |
36,230,689 | Expression, Localization and Prognosis Association of MEP50 in Breast Cancer. | Breast cancer is composed of distinct subgroups, triple-negative breast cancer (TNBC), human epidermal growth factor receptor-2 (HER2), luminal A, and luminal B, which are associated with different prognosis. MEP50 is the main partner of the arginine methyltransferase PRMT5 required for its enzymatic activity. Here, we examined |
36,230,683 | EZH2 Inhibition and Cisplatin as a Combination Anticancer Therapy An Overview of Preclinical Studies. | Anticancer monotherapies are often insufficient in eradicating cancer cells because cancers are driven by changes in numerous genes and pathways. Combination anticancer therapies which aim to target several cancer traits at once represent a substantial improvement in anticancer treatment. Cisplatin is a conventional chemotherapy agent widely used in the treatment of different cancer types. However, the shortcomings of cisplatin use include its toxicity and development of resistance. Therefore, from early on, combination therapies that include cisplatin were considered and used in a variety of cancers. EZH2, an epigenetic regulator, is frequently upregulated in cancers which, in general, potentiates cancer cell malignant behavior. In the past decade, numerous EZH2 inhibitors have been explored for their anticancer properties. In this overview, we present the studies that discuss the joint action of cisplatin and EZH2 inhibitors. According to the data presented, the use of cisplatin and EZH2 inhibitors may be beneficial in the treatment of lung, ovarian, and breast cancers, since there is a substantial amount of published evidence that suggests their concerted action. However, in testicular germ cell tumors, such a combination would not be recommended because cisplatin resistance seems to be associated with decreased expression of EZH2 in this tumor type. |
36,230,678 | Episodic Memory and Recollection Network Disruptions Following Chemotherapy Treatment in Breast Cancer Survivors A Review of Neuroimaging Findings. | Long-term memory disturbances are amongst the most common and disruptive cognitive symptoms experienced by breast cancer survivors following chemotherapy. To date, most clinical assessments of long-term memory dysfunction in breast cancer survivors have utilized basic verbal and visual memory tasks that do not capture the complexities of everyday event memories. Complex event memories, including episodic memory and autobiographical memory, critically rely on hippocampal processing for encoding and retrieval. Systemic chemotherapy treatments used in breast cancer commonly cause neurotoxicity within the hippocampus, thereby creating a vulnerability to memory impairment. We review structural and functional neuroimaging studies that have identified disruptions in the recollection network and related episodic memory impairments in chemotherapy-treated breast cancer survivors, and argue for the need to better characterize hippocampally mediated memory dysfunction following chemotherapy treatments. Given the importance of autobiographical memory for a persons sense of identity, ability to plan for the future, and general functioning, under-appreciation of how this type of memory is impacted by cancer treatment can lead to overlooking or minimizing the negative experiences of breast cancer survivors, and neglecting a cognitive domain that may benefit from intervention strategies. |
36,230,663 | A Large Case-Control Study Performed in Spanish Population Suggests That | Around 50% of the familial breast cancer (BC) cases are estimated to be caused by germline variants in known low-, moderate-, and high-risk susceptibility genes, while the other half is of unknown genetic origin. In the present study, we wanted to evaluate the role of the RECQ helicases, some of which have been studied in the past as candidates, with unclear results about their role in the disease. Using next-generation sequencing (NGS) technology, we analyzed the whole coding sequence of |
36,230,648 | The Impact of Race-Ethnicity and Diagnosis of Alzheimers Disease and Related Dementias on Mammography Use. | Breast cancer screening (BCS) with mammography is a crucial method for improving cancer survival. In this study, we examined the association of Alzheimers disease (AD) and AD-related dementias (ADRD) diagnosis and race-ethnicity with mammography use in BCS-eligible women. In the real-world data from the OneFlorida Clinical Research Network, we extracted a cohort of 21,715 BCS-eligible women with ADRD and a matching comparison cohort of 65,145 BCS-eligible women without ADRD. In multivariable regression analysis, BCS-eligible women with ADRD were more likely to undergo a mammography than the BCS-eligible women without ADRD (odds ratio OR 1.19, 95% confidence interval CI 1.13-1.26). Stratified by race-ethnicity, BCS-eligible Hispanic women with ADRD were more likely to undergo a mammography (OR 1.56, 95% CI 1.39-1.75), whereas BCS-eligible non-Hispanic black (OR 0.72, 95% CI 0.62-0.83) and non-Hispanic other (OR 0.65, 95% CI 0.45-0.93) women with ADRD were less likely to undergo a mammography. This study was the first to report the impact of ADRD diagnosis and race-ethnicity on mammography use in BCS-eligible women using real-world data. Our results suggest ADRD patients might be undergoing BCS without detailed guidelines to maximize benefits and avoid harms. |
36,230,639 | Mutation Patterns in Portuguese Families with Hereditary Breast and Ovarian Cancer Syndrome. | Germline pathogenic variants in the Breast Cancer Genes 1 ( |
36,230,628 | Clinical and Sociodemographic Determinants of Adherence to World Cancer Research FundAmerican Institute for Cancer Research (WCRFAICR) Recommendations in Breast Cancer Survivors-Health-EpiGEICAM Study. | Breast cancer (BC) survivors are advised to follow the WCRFAICR cancer prevention recommendations, given their high risk of developing a second tumour. We aimed to explore compliance with these recommendations in BC survivors and to identify potentially associated clinical and sociodemographic factors. A total of 420 BC survivors, aged 31-80, was recruited from 16 Spanish hospitals. Epidemiological, dietary and physical activity information was collected through questionnaires. A 7-item score to measure compliance with the recommendations was built according to the 2018 WCRFAICR scoring criteria. Standardized prevalences and standardized prevalence ratios of moderate and high compliance across participant characteristics were estimated using multinomial and binary logistic regression models. The mean score was 3.9 (SD 1.0) out of 7 points. Recommendations with the worst adherence were those of limiting consumption of redprocessed meats (12% of compliance, 95% CI 8.2-15.0) and high fibre intake (22% of compliance, 95% CI 17.6-27.0), while the best compliance was observed for the consumption of fruits and vegetables (73% of compliance, 95% CI 69.2-77.7). Overall, adherence was worse in women with university education and in those with first-degree relatives with BC. This information may be of interest to design and implement personalized preventive measures adapted to the characteristics of these patients. |
36,230,625 | Automated Assessment of Breast Positioning Quality in Screening Mammography. | Screening mammography is a widely used approach for early breast cancer detection, effectively increasing the survival rate of affected patients. According to the Food and Drug Administrations Mammography Quality Standards Act and Program statistics, approximately 39 million mammography procedures are performed in the United States each year. Therefore, breast cancer screening is among the most common radiological tasks. Interpretation of screening mammograms by a specialist radiologist includes primarily the review of breast positioning quality, which is a key factor affecting the sensitivity of mammography and thus the diagnostic performance. Each mammogram with inadequate positioning may lead to a missed cancer or, in case of false positive signal interpretation, to follow-up activities, increased emotional burden and potential over-therapy and must be repeated, requiring the return of the patient. In this study, we have developed deep convolutional neuronal networks to differentiate mammograms with inadequate breast positioning from the adequate ones. The aim of the proposed automated positioning quality evaluation is to assist radiology technologists in detecting poorly positioned mammograms during patient visits, improve mammography performance, and decrease the recall rate. The implemented models have achieved 96.5% accuracy in cranio-caudal view classification and 93.3% accuracy in mediolateral oblique view regarding breast positioning quality. In addition to these results, we developed a software module that allows the study to be applied in practice by presenting the implemented model predictions and informing the technologist about the missing quality criteria. |
36,230,619 | FOXA1 in Breast Cancer A Luminal Marker with Promising Prognostic and Predictive Impact. | The present review focuses on the function of the forkhead protein FOXA1 in breast cancer (BC) in relation to steroid hormone receptors. We explored the currently available analytic approaches for FOXA1 assessment both at gene and protein levels, comparing the differences between the available techniques used for its diagnostic assessment. In addition, we elaborated on data regarding the prognostic and predictive role of this marker in BC based on several studies that evaluated its expression in relation to the outcome andor response to therapy. FOXA1, similar to the androgen receptor (AR), may have a dual role in BC according to hormonal status. In luminal cancers, its expression contributes to a better prognosis, while in triple-negative breast cancers (TNBC), it implies an adverse outcome. Consequently, we observed that FOXA1-positive expression in a neoadjuvant setting may predict a lack of response in luminal BC as opposed to TNBC, in which FOXA1 allegedly increases its chemosensitivity. In conclusion, considering its accessible and convenient identification by immunohistochemistry, its important impact on prognosis, and its suitability to identify patients with different responses to chemotherapy, we propose that FOXA1 could be tested in routine diagnostics as an additional prognostic and predictive marker in BC. |
36,230,606 | Symptom Management and Quality of Life of Breast Cancer Patients Using Acupuncture-Related Therapies and Herbal Medicine A Scoping Review. | The side effects associated with breast cancer treatments often reduce the patients quality of life. The effectiveness of acupuncture-related therapies and herbal medicine in managing the side effect is not fully understood. The study included clinical studies published in the 10 years since 2011 and analyzed the effectiveness of the therapies for managing side effects of anticancer treatment. The databases of MEDLINE via PubMed, CENTRAL, EMBASE, OASIS, and NSDL were searched. Thirty studies, including 13 (43.3%) randomized controlled trials (RCTs), 12 (40.0%) before-and-after studies, three (10.0%) case series, one (3.3%) case report, and one (3.3%) non-RCT, were included in this review. The main symptoms identified were aromatase inhibitors-induced arthralgia (AIA), lymphedema, and chemotherapy-induced peripheral neuropathy (CIPN). The types of acupuncture-related therapies applied included manual acupuncture, electro-acupuncture, moxibustion, and electro-moxibustion. In ten studies, eight herbal medications were administered. The Brief Pain Inventory-Short Form (BPI-SF) and Functional Assessment of Cancer Therapy-General (FACT-G) and -Breast (FACT-B) were frequently used to evaluate pain and QoL, respectively. Most studies suggested beneficial effects of acupuncture and herbal medicine on managing pain, daily function, and quality of life in patients going through AIA, CIPN, andor lymphedema, with mild side effects. The scoping review implies the potential of CAM therapies as promising interventions for managing symptoms which otherwise lack alternative management options, and for improving the quality of life of breast cancer patients. |
36,230,591 | Ethanol Ablation Therapy Drives Immune-Mediated Antitumor Effects in Murine Breast Cancer Models. | Ethanol ablation is a minimally invasive, cost-effective method of destroying tumor tissue through an intratumoral injection of high concentrations of cytotoxic alcohol. Ethyl-cellulose ethanol (ECE) ablation, a modified version of ethanol ablation, contains the phase-changing polysaccharide ethyl-cellulose to reduce ethanol leakage away from the tumor. Ablation produces tissue necrosis and initiates a wound healing process however, the characteristic of the immunologic events after ECE ablation of tumors has yet to be explored. Models of triple-negative breast cancer (TNBC), which are classically immunosuppressive and difficult to treat clinically, were used to characterize the immunophenotypic changes after ECE ablation. In poorly invasive TNBC rodent models, the injury to the tumor induced by ECE increased tumor infiltrating lymphocytes (TILs) and reduced tumor growth. In a metastatic TNBC model (4T1), TILs did not increase after ECE ablation, though lung metastases were reduced. 4T1 tumors secrete high levels of granulocytic colony stimulating factor (G-CSF), which induces a suppressive milieu of granulocytic myeloid-derived suppressor cells (gMDSCs) aiding in the formation of metastases and suppression of antitumor immunity. We found that a single intratumoral injection of ECE normalized tumor-induced myeloid changes reducing serum G-CSF and gMDSC populations. ECE also dampened the suppressive strength of gMDSC on CD4 and CD8 cell proliferation, which are crucial for anti-tumor immunity. To demonstrate the utility of these findings, ECE ablation was administered before checkpoint inhibitor (CPI) therapy in the 4T1 model and was found to significantly increase survival compared to a control of saline and CPI. Sixty days after tumor implant no primary tumors or metastatic lung lesions were found in 610 mice treated with CPI plus ECE, compared to 110 with ECE alone and 010 with CPI and saline. |
36,230,587 | Pharmacogenomics for Prediction of Cardiovascular Toxicity Landscape of Emerging Data in Breast Cancer Therapies. | Pharmacogenomics is an emerging field in oncology, one that could provide valuable input on identifying patients with inherent risk of toxicity, thus allowing for treatment tailoring and personalization on the basis of the clinical and genetic characteristics of a patient. Cardiotoxicity is a well-known side effect of anthracyclines and anti-HER2 agents, although at a much lower incidence for the latter. Data on single-nucleotide polymorphisms related to cardiotoxicity are emerging but are still scarce, mostly being of retrospective character and heterogeneous. A literature review was performed, aiming to describe current knowledge in pharmacogenomics and prediction of cardiotoxicity related to breast cancer systemic therapies and radiotherapies. Most available data regard genes encoding various enzymes related to anthracycline metabolism and HER2 polymorphisms. The available data are presented, together with the challenges and open questions in the field. |
36,230,586 | Investigation of the Role of PUFA Metabolism in Breast Cancer Using a Rank-Based Random Forest Algorithm. | Polyunsaturated fatty acid (PUFA) metabolism is currently a focus in cancer research due to PUFAs functioning as structural components of the membrane matrix, as fuel sources for energy production, and as sources of secondary messengers, so called oxylipins, important players of inflammatory processes. Although breast cancer (BC) is the leading cause of cancer death among women worldwide, no systematic study of PUFA metabolism as a system of interrelated processes in this disease has been carried out. Here, we implemented a Boruta-based feature selection algorithm to determine the list of most important PUFA metabolism genes altered in breast cancer tissues compared with in normal tissues. A rank-based Random Forest (RF) model was built on the selected gene list (33 genes) and applied to predict the cancer phenotype to ascertain the PUFA genes involved in cancerogenesis. It showed high-performance of dichotomic classification (balanced accuracy of 0.94, ROC AUC 0.99) We also retrieved a list of the important PUFA genes (46 genes) that differed between molecular subtypes at the level of breast cancer molecular subtypes. The balanced accuracy of the classification model built on the specified genes was 0.82, while the ROC AUC for the sensitivity analysis was 0.85. Specific patterns of PUFA metabolic changes were obtained for each molecular subtype of breast cancer. These results show evidence that (1) PUFA metabolism genes are critical for the pathogenesis of breast cancer (2) BC subtypes differ in PUFA metabolism genes expression and (3) the lists of genes selected in the models are enriched with genes involved in the metabolism of signaling lipids. |
36,230,582 | Adequacy of Pain Treatment in Radiotherapy Departments Results of a Multicenter Study on 2104 Patients (Arise). | The frequent inadequacy of pain management in cancer patients is well known. Moreover, the quality of analgesic treatment in patients treated with radiotherapy (RT) has only been rarely assessed. In order to study the latter topic, we conducted a multicenter, observational and prospective study based on the Pain Management Index (PMI) in RT Italian departments. We collected data on age, gender, tumor site and stage, performance status, treatment aim, and pain (type CP-cancer pain, NCP-non-cancer pain, MP-mixed pain intensity NRS Numeric Rating Scale). Furthermore, we analyzed the impact on PMI on these parameters, and we defined a pain score with values from 0 (NRS 0, no pain) to 3 (NRS 7-10 intense pain) and an analgesic score from 0 (pain medication not taken) to 3 (strong opioids). By subtracting the pain score from the analgesic score, we obtained the PMI value, considering cases with values lt 0 as inadequate analgesic prescriptions. The Ethics Committees of the participating centers approved the study (ARISE-1 study). Two thousand one hundred four non-selected outpatients with cancer and aged 18 years or older were enrolled in 13 RT departments. RT had curative and palliative intent in 62.4% and 37.6% patients, respectively. Tumor stage was non-metastatic in 57.3% and metastatic in 42.7% of subjects, respectively. Pain affected 1417 patients (CP 49.5%, NCP 32.0% MP 18.5%). PMI was lt 0 in 45.0% of patients with pain. At multivariable analysis, inadequate pain management was significantly correlated with curative RT aim, ECOG performance status 1 (versus both ECOG-PS3 and ECOG- PS4), breast cancer, non-cancer pain, and Central and South Italy RT Departments (versus Northern Italy). Pain management was less adequate in patients with more favorable clinical condition and stage. Educational and organizational strategies are needed in RT departments to reduce the non-negligible percentage of patients with inadequate analgesic therapy. |
36,230,572 | The Histone Demethylase HR Suppresses Breast Cancer Development through Enhanced CELF2 Tumor Suppressor Activity. | The |
36,230,559 | Implementing Risk-Stratified Breast Screening in England An Agenda Setting Meeting. | It is now possible to accurately assess breast cancer risk at routine NHS Breast Screening Programme (NHSBSP) appointments, provide risk feedback and offer risk management strategies to women at higher risk. These strategies include National Institute for Health and Care Excellence (NICE) approved additional breast screening and risk-reducing medication. However, the NHSBSP invites nearly all women three-yearly, regardless of risk. In March 2022, a one-day agenda setting meeting took place in Manchester to discuss the feasibility and desirability of implementation of risk-stratified screening in the NHSBSP. Fifty-eight individuals participated (38 face-to-face, 20 virtual) with relevant expertise from academic, clinical andor policy-making perspectives. Key findings were presented from the PROCAS2 NIHR programme grant regarding feasibility of risk-stratified screening in the NHSBSP. Participants discussed key uncertainties in seven groups, followed by a plenary session. Discussions were audio-recorded and thematically analysed to produce descriptive themes. Five themes were developed (i) risk and health economic modelling (ii) health inequalities and communication with women (iii) extending screening intervals for low-risk women (iv) integration with existing NHSBSP and (v) potential new service models. Most attendees expected some form of risk-stratified breast screening to be implemented in England and collectively identified key issues to be resolved to facilitate this. |
36,230,540 | Breast-Specific Gamma Imaging An Added Value in the Diagnosis of Breast Cancer, a Systematic Review. | Breast cancer is the most common solid tumor and the second highest cause of death in the United States. Detection and diagnosis of breast tumors includes various imaging modalities, such as mammography (MMG), ultrasound (US), and contrast-enhancement MRI. Breast-specific gamma imaging (BSGI) is an emerging tool, whereas morphological imaging has the disadvantage of a higher absorbed dose. Our aim was to assess if this imaging method is a more valuable choice in detecting breast malignant lesions compared to morphological counterparts. research on Medline from 1995 to June 2022 was conducted. Studies that compared at least one anatomical imaging modality with BSGI were screened and assessed through QUADAS2 for risk of bias and applicability concerns assessment. Sensitivity, specificity, positive and negative predictive value (PPV and NPV) were reported. A total of 15 studies compared BSGI with MMG, US, and MRI. BSGI sensitivity was similar to MRI, but specificity was higher. Specificity was always higher than MMG and US. BSGI had higher PPV and NPV. When used for the evaluation of a suspected breast lesion, the overall sensitivity was better than the examined overall sensitivity when BSGI was excluded. Risk of bias and applicability concerns domain showed mainly low risk of bias. BSGI is a valuable imaging modality with similar sensitivity to MRI but higher specificity, although at the cost of higher radiation burden. |
36,230,537 | Targeted Depletion of Hyaluronic Acid Mitigates Murine Breast Cancer Growth. | Hyaluronic acid (HA) is highly elevated in breast cancers compared to normal breast tissue and is associated with increased tumor aggressiveness and poor prognosis. HA interacts with cell-trafficking CD44 receptors to promote tumor cell migration and proliferation and regulates both pro- and anti-inflammatory cytokine production through tumor-associated macrophages. The highly negative charge of HA enables its uptake of vast amounts of water that greatly increases the tumor interstitial fluidic pressure, which, combined with the presence of other extracellular matrix components such as collagen, results in tumor stroma with abnormal vasculature, hypoxia, and increased drug resistance. Thus, the degradation of HA in breast cancer may attenuate growth and improve permeability to anticancer agents. Previous methods to deplete tumor HA have resulted in significant off-tumor effects due to the systemic use of mammalian hyaluronidases. To overcome this, we developed a hyaluronidase-secreting |
36,230,512 | Controversies and Open Questions in Management of Cancer-Free Carriers of Germline Pathogenic Variants in | Females harboring germline |
36,230,510 | Whats beyond BRCA Mutational Status in High Grade Serous Ovarian Cancer The Impact of Hormone Receptor Expression in a Large BRCA-Profiled Ovarian Cancer Patient Series A Retrospective Cohort Study. | Several studies have explored the prognostic role of hormone receptor status in high-grade serous ovarian cancer (HGSOC) patients. However, few reports have investigated their expression according to BRCA mutational status. The aim of this single-center, observational, retrospective study was to explore the hormone receptor pattern and its potential prognostic role in a cohort of 207 HGSOC women stratified for BRCA mutational status. To this end, ERα, ERβ1, ERβ2, ERβ5, PR, and AR expression were assessed by immunohistochemistry in 135 BRCA-wild type (BRCA-wt) and 72 BRCA12 mutation carriers (BRCA-mut). No significant difference emerged in hormone receptor expression between the two sub-samples, except for a significantly lower ERα expression observed in pre-menopausal BRCA12-mut as compared to BRCA-wt patients ( |
36,230,508 | Modulation of Fibroblast Activity via Vitamin D | Vitamin D |
36,230,497 | CNN-Based Approaches with Different Tumor Bounding Options for Lymph Node Status Prediction in Breast DCE-MRI. | The axillary lymph node status (ALNS) is one of the most important prognostic factors in breast cancer (BC) patients, and it is currently evaluated by invasive procedures. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), highlights the physiological and morphological characteristics of primary tumor tissue. Deep learning approaches (DL), such as convolutional neural networks (CNNs), are able to autonomously learn the set of features directly from images for a specific task. A total of 155 malignant BC lesions evaluated via DCE-MRI were included in the study. For each patients clinical data, the tumor histological and MRI characteristics and axillary lymph node status (ALNS) were assessed. LNS was considered to be the final label and dichotomized (LN (27 patients) vs. LN- (128 patients)). Based on the concept that peritumoral tissue contains valuable information about tumor aggressiveness, in this work, we analyze the contributions of six different tumor bounding options to predict the LNS using a CNN. These bounding boxes include a single fixed-size box (SFB), a single variable-size box (SVB), a single isotropic-size box (SIB), a single lesion variable-size box (SLVB), a single lesion isotropic-size box (SLIB), and a two-dimensional slice (2DS) option. According to the characteristics of the volumes considered as inputs, three different CNNs were investigated the SFB-NET (for the SFB), the VB-NET (for the SVB, SIB, SLVB, and SLIB), and the 2DS-NET (for the 2DS). All the experiments were run in 10-fold cross-validation. The performance of each CNN was evaluated in terms of accuracy, sensitivity, specificity, the area under the ROC curve (AUC), and Cohens kappa coefficient (K). The best accuracy and AUC are obtained by the 2DS-NET (78.63% and 77.86%, respectively). The 2DS-NET also showed the highest specificity, whilst the highest sensibility was attained by the VB-NET based on the SVB and SIB as bounding options. We have demonstrated that a selective inclusion of the DCE-MRIs peritumoral tissue increases accuracy in the lymph node status prediction in BC patients using CNNs as a DL approach. |
36,230,495 | BRCA Mutation Status in Triple-Negative Breast Cancer Patients Treated with Neoadjuvant Chemotherapy A Pivotal Role for Treatment Decision-Making. | Triple-negative breast cancer (TNBC) is characterized by earlier recurrence and shorter survival compared with other types of breast cancer. Moreover, approximately 15 to 25% of all TNBC patients harbor germline BRCA (gBRCA) 12 mutations, which confer a more aggressive phenotype. However, TNBC seems to be particularly sensitive to chemotherapy, the so-called triple negative paradox. Therefore, Neoadjuvant chemotherapy (NACT) is currently considered the preferred approach for early-stage TNBC. BRCA status has also been studied as a predictive biomarker of response to platinum compounds. Although several randomized trials investigated the addition of carboplatin to standard NACT in early-stage TNBC, the role of BRCA status remains unclear. In this retrospective analysis, we evaluated data from 136 consecutive patients with Stage I-III TNBC who received standard NACT with or without the addition of carboplatin, in order to define clinical features and outcomes in BRCA 12 mutation carriers and non-carrier controls. Between January 2013 and February 2021, 67 (51.3%) out of 136 patients received a standard anthracyclinestaxane regimen and 69 (50.7%) patients received a platinum-containing chemotherapy regimen. Deleterious germline BRCA1 or BRCA2 mutations were identified in 39 (28.7%) patients. Overall, patients with deleterious gBRCA12 mutation have significantly higher pCR rate than non-carrier patients (23 59% of 39 vs. 33 34% of 97 |
36,230,488 | The Association between Smoking and Mortality in Women with Breast Cancer A Real-World Database Analysis. | Smoking increases the cancer-specific and overall mortality risk in women with breast cancer (BC). However, the effect of smoking cessation remains controversial, and detailed research is lacking in Asia. We aimed to investigate the association between smoking status and mortality in women with BC using the population-based cancer registry. The Taiwan Cancer Registry was used to identify women with BC from 2011 to 2017. A total of 54,614 women with BC were enrolled, including 1687 smokers and 52,927 non-smokers. The outcome, mortality, was identified using Taiwans cause-of-death database. The association between smoking status and mortality was estimated using Cox proportional regression. Women with BC who smoked had a 1.25-fold higher (95% C.I. 1.08-1.45 |
36,230,483 | Prognostic Relevance of Nuclear Receptors in Relation to Peritumoral Inflammation and Tumor Infiltration by Lymphocytes in Breast Cancer. | The prognostic impact of tumor-infiltrating lymphocytes (TILs) is intensively investigated in breast cancer (BC). It is already known that triple-negative breast cancer (TNBC), the most aggressive type of BC, has the highest percentage of TILs. In addition, there is an influence of steroid hormone receptor expression (type I nuclear receptors) on TIL subpopulations in breast cancer tissue. The link between type II nuclear receptors and the level of TILs is unclear. Therefore, the aim of this study was to quantify TILs in a panel of 264 sporadic breast cancers and investigate the correlation of TIL levels with type I and II nuclear receptors expression. TIL levels were significantly increased in the subgroup of TNBC. By contrast, they decreased in estrogen (ER)- or progesterone receptor (PR)-positive cases. Moreover, TIL levels were correlated with type II nuclear receptors, including PPARγ, with a significant inverse correlation of the nuclear form (r -0.727, |
36,230,471 | Prognostic Value of the Serum HER2 Extracellular Domain Level in Breast Cancer A Systematic Review and Meta-Analysis. | An elevated serum HER2 extracellular domain is associated with poor prognosis in breast cancer, but the relationship between sHER2 and the efficacy of different modalities remains controversial. Herein, we aimed to evaluate the prognostic value of serum HER2 extracellular domain (sHER2 ECD) in breast cancer and to identify its correlation with the efficacy of different treatment regimens. A systematic search of the PubMed, Embase, Cochrane Library, Web of Science, and Scopus databases was conducted to identify studies exploring the association between HER2 ECD level and clinical outcomes among patients with breast cancer. Using the random effects models, pooled hazard ratios (HRs), and odds ratios (ORs) with 95% confidence intervals (CI), were calculated for progression-free survival (PFS), overall survival (OS), disease-free survival (DFS), and the objective response rate (ORR). Heterogeneity was further evaluated by subgroup and sensitivity analysis. Overall, 40 studies comprising 12,229 patients were included in this systematic review and meta-analysis. Elevated HER2 ECD levels were associated with worse PFS (HR 1.74, 95% CI 1.40-2.17 |
36,230,468 | De-Escalating the Management of In Situ and Invasive Breast Cancer. | It is necessary to identify appropriate areas of de-escalation in breast cancer treatment to minimize morbidity and maximize patients quality of life. Less radical treatment modalities, or even no treatment, have been reconsidered if they offer the same oncologic outcomes as standard therapies. Identifying which patients benefit from de-escalation requires particular care, as standard therapies will continue to offer adequate cancer outcomes. We provide an overview of the literature on the de-escalation of treatment of ductal carcinoma in situ (DCIS), local treatment of breast cancer, and surgery after neoadjuvant systemic therapy. De-escalation of breast cancer treatment is a key area of investigation that will continue to remain a priority. Improvements in understanding the natural history and biology of breast cancer, imaging modalities, and adjuvant treatments will expand this even further. Future efforts will continue to challenge us to consider the true role of various treatment modalities. |
36,229,957 | Adjuvant 5-Fluorouracilleucovorin, capecitabine, and oxaliplatin-related regimens for stage IIIII colon cancer patients 66 years or older. | Adjuvant chemotherapy of leucovorin-modulated 5-fluorouracil (5-FULV), capecitabine, and adding oxaliplatin to 5-FULV or capecitabine (FLOXOX) have been standard regimens for high-risk stage II or III colon cancer (CC). We aimed to evaluate their patterns of use, association with survival, and rate of emergency room visit (ER) or hospitalization during the treatment period. High-risk stage II or III patients aged >65 years diagnosed between 2007 and 2015, underwent colectomy, and received any of these three regimens were selected from SEER and Texas Cancer Registry (TC) linked with Medicare data. Chi-square test, Kaplan-Meier survival curves, Cox regression, and logistic regression were used in data analysis. A total of 5621 (1080 stage II and 4541 stage III) patients with median age of 72 years were included in this study. For stage II, 24.4% used 5-FULV, 31.2% used capecitabine, and 44.4% used FLOXOX the respective numbers for stage III were 13.8%, 17.9%, and 68.3%. Patients aged <70 years, not in the West region, not in Medicare state-buy-in program, and with no comorbidity were more likely to use FLOXOX. FLOXOX was associated with improved overall survival (OS) in stage II and III patients and improved cancer-specific survival in stage III patients compared with 5-FULV. The survival benefit of FLOXOX was sustained in stage III patients aged ≥70 years. Capecitabine had the lowest ERhospitalization rate with 19.2% in stage II and 28.9% in III. The use of FLOXOX was associated with improved survival compared with 5-FULV among CC patients. Capecitabine was associated with the lowest ERhospitalization rate. |
36,229,909 | The Korea Cohort Consortium The Future of Pooling Cohort Studies. | We introduced the cohort studies included in the Korea Cohort Consortium (KCC), focusing on large-scale cohort studies established in Korea with a prolonged follow-up period. Moreover, we also provided projections of the follow-up and estimates of the sample size that would be necessary for big-data analyses based on pooling established cohort studies, including population-based genomic studies. We mainly focused on the characteristics of individual cohort studies from the KCC. We developed PROFAN, a Shiny application for projecting the follow-up period to achieve a certain number of cases when pooling established cohort studies. As examples, we projected the follow-up periods for 5000 cases of gastric cancer, 2500 cases of prostate and breast cancer, and 500 cases of non-Hodgkin lymphoma. The sample sizes for sequencing-based analyses based on a 11 case-control study were also calculated. The KCC consisted of 8 individual cohort studies, of which 3 were community-based and 5 were health screening-based cohorts. The population-based cohort studies were mainly organized by Korean government agencies and research institutes. The projected follow-up period was at least 10 years to achieve 5000 cases based on a cohort of 0.5 million participants. The mean of the minimum to maximum sample sizes for performing sequencing analyses was 5917-72 102. We propose an approach to establish a large-scale consortium based on the standardization and harmonization of existing cohort studies to obtain adequate statistical power with a sufficient sample size to analyze high-risk groups or rare cancer subtypes. |
36,229,894 | Water and lipid content of breast tissue measured by six-wavelength time-domain diffuse optical spectroscopy. | The water and lipid content of normal breast tissue showed mammary gland characteristics with less influence from the chest wall using six-wavelength time-domain diffuse optical spectroscopy (TD-DOS) in a reflectance geometry. To determine the depth sensitivity of a six-wavelength TD-DOS system and evaluate whether the optical parameters in normal breast tissue can distinguish dense breasts from non-dense breasts. Measurements were performed in normal breast tissue of 37 breast cancer patients. We employed a six-wavelength TD-DOS system to measure the water and lipid content in addition to the hemoglobin concentration. The breast density in mammography and optical parameters were then compared. The depth sensitivity of the system for water and lipid content was estimated to be ∼15 mm. Our findings suggest that the influence of the chest wall on the water content is weaker than that on the total hemoglobin concentration. In data with evaluation conditions, the water content was significantly higher (p < 0.001) and the lipid content was significantly lower (p < 0.001) in dense breast tissue. The water and lipid content exhibited a high sensitivity and specificity to distinguish dense from non-dense breasts in receiver-operating-characteristic curve analysis. With less influence from the chest wall, the water and lipid content of normal breast tissue measured by a reflectance six-wavelength TD-DOS system, together with ultrasonography, can be applied to distinguish dense from non-dense breasts. |
36,229,876 | Prediction models for breast cancer-related lymphedema a systematic review and critical appraisal. | The development of risk prediction models for breast cancer lymphedema is increasing, but few studies focus on the quality of the model and its application. Therefore, this study aimed to systematically review and critically evaluate prediction models developed to predict breast cancer-related lymphedema. PubMed, Web of Science, Embase, MEDLINE, CNKI, Wang Fang DATA, Vip Database, and SinoMed were searched for studies published from 1 January 2000 to 1 June 2021. And it will be re-run before the final analysis. Two independent investigators will undertake the literature search and screening, and discrepancies will be resolved by another investigator. The Prediction model Risk Of Bias Assessment Tool will be used to assess the prediction models risk of bias and applicability. Seventeen studies were included in the systematic review, including 7 counties, of which 6 were prospective studies, only 7 models were validation studies, and 4 models were externally validated. The area under the curve of 17 models was 0.6800.908. All studies had a high risk of bias, primarily due to the participants, outcome, and analysis. The most common predictors included body mass index, radiotherapy, chemotherapy, and axillary lymph node dissection. The predictive factors strength, external validation, and clinical application of the breast cancer lymphedema risk prediction model still need further research. Healthcare workers should choose prediction models in clinical practice judiciously. PROSPERO CRD42021258832. |
36,229,870 | Process development for the total synthesis of the novel drug metabolite Carboxy toremifene as a standard reference material along with characterization and purity assessment for the Antidoping quality Control Purposes. | Tamoxifen and toremifene are two selective estrogen receptor modulators (SERMs) commonly used to treat breast cancer in women. Toremifene is well-known as a triphenylethylene derivative. Carboxy toremifene is a common metabolite of toremifene and tamoxifen. Since 2005, the World Anti-Doping Agency (WADA) has banned the SERMs category during in and out of competition. These substances are in the S4 category in the WADA prohibited list as agents with anti-oestrogenic activity. However, there is no commercially accessible carboxy toremifene reference material in the market. This research highlights the novel synthetic procedure, the development of a carboxy toremifene HPLC method, and validation, along with detailed characterization using advanced analytical techniques using |
36,229,841 | Overall survival of individuals with metastatic cancer in Sweden a nationwide study. | Consistent improvements for overall survival (OS) have been reported for individuals with metastatic cancer. Swedish population-based registers allow national coverage and long follow-up time. The aim of this study was to estimate and explore long-term OS of individuals diagnosed with metastatic cancer using Swedish nationwide health registers. Individuals with metastatic breast (MBC), non-small cell lung (MNSCLC), ovary (MOC) or colorectal cancer (MCRC) or metastatic malignant melanoma (MMM) were identified in the Swedish national cancer register and national patient registers. Survival was estimated and stratified by available variables. Potential cure fractions were estimated using mixture cure models. In total, approximately 69,000 individuals were identified. The most common cancers were MCRC (36.2%) and MNSCLC (29.5%). Men were more frequently diagnosed with MNSCLC, MCRC, and MMM compared to women. Except for MOC, about 50% of individuals were 70 years or older at diagnosis. Throughout the study period survival differed across cancers. The longest median OS was observed for individuals with MOC and MBC. At 10 years of follow-up, the survival curves flatten at a survival rate of approximately 10% for all cancers except MNSCLC. The youngest age groups had the longest median OS. Increased survival was also observed for individuals diagnosed in 2015 and 2018 compared to individuals diagnosed during earlier years. The estimated cure fractions were 4% for MBC, 1.5% for MNSCLC, 6.8% for MCRC, 8.6% for MOC and MMM. Long-term survival has been assessed across all indications except for NSCLC.. The findings may be relevant for healthcare planning to meet the needs of future patients and potential long-term survivors. |
36,229,838 | FOXD1-dependent RalA-ANXA2-Src complex promotes CTC formation in breast cancer. | Early metastasis is a key factor contributing to poor breast cancer (BC) prognosis. Circulating tumor cells (CTCs) are regarded as the precursor cells of metastasis, which are ultimately responsible for the main cause of death in BC. However, to date molecular mechanisms underlying CTC formation in BC have been insufficiently defined. RNA-seq was carried out in primary tissues from early-stage BC patients (with CTCs≥5 and CTCs 0, respectively) and the validation study was conducted in untreated 80 BC patients. Multiple in vitro and in vivo models were used in functional studies. Luciferase reporter, ChIP-seq, CUTTag-seq, and GST-pulldown, etc. were utilized in mechanistic studies. CTCs were counted by the CanPatrol™ CTC classification system or LiquidBiospy™ microfluidic chips. ERK12 inhibitor SCH772984 was applied to in vivo treatment. Highly expressed FOXD1 of primary BC tissues was observed to be significantly associated with increased CTCs in BC patients, particularly in early BC patients. Overexpressing FOXD1 enhanced the migration capability of BC cells, CTC formation and BC metastasis, via facilitating epithelial-mesenchymal transition of tumor cells. Mechanistically, FOXD1 was discovered to induce RalA expression by directly bound to RalA promotor. Then, RalA formed a complex with ANXA2 and Src, promoting the interaction between ANXA2 and Src, thus increasing the phosphorylation (Tyr23) of ANXA2. Inhibiting RalA-GTP form attenuated the interaction between ANXA2 and Src. This cascade culminated in the activation of ERK12 signal that enhanced metastatic ability of BC cells. In addition, in vivo treatment with SCH772984, a specific inhibitor of ERK12, was used to dramatically inhibit the CTC formation and BC metastasis. Here, we report a FOXD1-dependent RalA-ANXA2-Src complex that promotes CTC formation via activating ERK12 signal in BC. FOXD1 may serve as a prognostic factor in evaluation of BC metastasis risks. This signaling cascade is druggable and effective for overcoming CTC formation from the early stages of BC. |
36,229,833 | A review on the role of LINC00467 in the carcinogenesis. | LINC00467 is an example of long intergenic non-coding RNAs whose roles in human disorders are being identified. This gene coding LINC00467 is located on chromosome 1 211,382,736 - 211,435,570 forward strand. This lncRNA has been firstly recognized through a microarray-based lncRNA profiling as an N-Myc target in neuroblastoma cells. Further studies have shown up-regulation of LINC00467 in different cancer including those originated from brain, gastrointestinal tract, lung and breast. It acts as a molecular sponge for miR-339, miR-138-5p, miR-107, miR-133b, miR-451a, miR-485-5p, miR-7-5p, miR-485-5p, miR-339-3p, miR-200a, miR-1285-3p, miR-299-5p, miR-509-3p, miR-18a-5p, miR-9-5p and miR-20b-5p. LINC00467 can regulate activity of NF-κB, STAT1, Wntb-catenin, Akt and ERK12 signaling pathways. Accumulating evidence indicates oncogenic role of LINC00467. The current review article aims at providing an overview of LINC00467 in the carcinogenesis. |
36,229,788 | A stabilized spatiotemporal kriging method for disease mapping and application to male oral cancer and female breast cancer in Taiwan. | Mapping spacetime disease rates can provide a more in-depth understanding of their distribution and trends. Traditional spatiotemporal kriging methods can break the constraints of geopolitical boundaries and time intervals. Still, disease rates in densely and sparsely populated areas are stabilized to the same degree, resulting in a map that is oversmoothed in some places but undersmoothed in others. The stabilized spatiotemporal kriging method proposed in this study overcomes this problem by allowing for nonconstant variances over space and time. A spatiotemporal map of the standardized incidence ratio for oral cancer in men in Taiwan between 1997 and 2017 reveals that the high-risk areas for oral cancer are in the midwestern and southeastern regions of Taiwan, spreading toward the center and north, with persistent cold spots in the northern and southwestern urban regions. However, the corresponding map for breast cancer in women in Taiwan reveals that the high-risk areas for breast cancer are concentrated in densely populated urban regions in the west. Spatiotemporal maps facilitate our understanding of disease risk dynamics. We recommend using the proposed stabilized spatiotemporal kriging method for mapping disease rates across space and time. |
36,229,710 | The race to develop oral SERDs and other novel estrogen receptor inhibitors recent clinical trial results and impact on treatment options. | Hormonal therapy plays a vital part in the treatment of estrogen receptor-positive (ER ) breast cancer. ER can be activated in a ligand-dependent and independent manner. Currently available ER-targeting agents include selective estrogen receptor modulators (SERMs), selective estrogen receptor degraders (SERDs), and aromatase inhibitors (AIs). Estrogen receptor mutation (ESR1 mutation) is one of the common mechanisms by which breast cancer becomes resistant to additional therapies from SERMs or AIs. These tumors remain sensitive to SERDs such as fulvestrant. Fulvestrant is limited in clinical utilization by its intramuscular formulation and once-monthly injection in large volumes. Oral SERDs are being rapidly developed to replace fulvestrant with the potential of higher efficacy and lower toxicities. Elacestrant is the first oral SERD that went through a randomized phase III trial showing increased efficacy, especially in tumors bearing ESR1 mutation, and good tolerability. Two other oral SERDs recently failed to achieve the primary endpoints of longer progression-free survival (PFS). They targeted tumors previously treated with several lines of prior therapies untested for ESR1 mutation. Initial clinical trial data demonstrated that tumors without the ESR1 mutation are less likely to benefit from the SERDs and may still respond to SERMs or AIs, including tumors previously exposed to hormonal therapy. Testing for ESR1 mutation in ongoing clinical trials and in hormonal therapy for breast cancer is highly recommended. Novel protein degradation technologies such as proteolysis-targeting chimera (PROTACS), molecular glue degrader (MGD), and lysosome-targeting chimeras (LYTACS) may result in more efficient ER degradation, while ribonuclease-targeting chimeras (RIBOTAC) and small interfering RNA (siRNA) may inhibit the production of ER protein. |
36,229,656 | Surface-guided DIBH radiotherapy for left breast cancer impact of different thresholds on intrafractional motion monitoring and DIBH stability. | To compare two left breast cancer patient cohorts (tangential vs. locoregional deep-inspiration breath-hold - DIBH treatment) with different predefined beam gating thresholds and to evaluate their impact on motion management and DIBH stability. An SGRT-based clinical workflow was adopted for the DIBH treatment. Intrafractional monitoring was performed by tracking both the respiratory signal and the real-time displacement between the isocenter on the daily reference surface and on the live surface (SGRT shift). Beam gating tolerances were 5 mm4 mm for the SGRT shifts and 5 mm3 mm for the gating window amplitude for breast tangential and breast lymph nodes locoregional treatments, respectively. A total of 24 patients, 12 treated with a tangential technique and 12 with a locoregional technique, were evaluated for a total number of 684 fractions. Statistical distributions of SGRT shift and respiratory signal for each treatment fraction, for each patient treatment, and for the two population samples were generated. Lateral cumulative distributions of SGRT shifts for both locoregional and tangential samples were consistent with a null shift, whereas longitudinal and vertical ones were slightly negative (mean values < 1 mm). The distribution of the percentage of beam on time with SGRT shift > 3 mm, > 4 mm, or > 5 mm was extended toward higher values for the tangential sample than for the locoregional sample. The variability in the DIBH respiration signal was significantly greater for the tangential sample. Different beam gating thresholds for surface-guided DIBH treatment of left breast cancer can impact motion management and DIBH stability by reducing the frequency of the maximum SGRT shift and increasing respiration signal stability when tighter thresholds are adopted. |
36,229,616 | Traceless cysteine-linchpin enables precision engineering of lysine in native proteins. | The maintenance of machinery requires its operational understanding and a toolbox for repair. The methods for the precision engineering of native proteins meet a similar requirement in biosystems. Its success hinges on the principles regulating chemical reactions with a protein. Here, we report a technology that delivers high-level control over reactivity, chemoselectivity, site-selectivity, modularity, dual-probe installation, and protein-selectivity. It utilizes cysteine-based chemoselective Linchpin-Directed site-selective Modification of lysine residue in a protein (LDM |
36,229,588 | Breast cancer risk coordinators Artificial intelligence-based density measurement and Mullerian-inhibiting substance. | Due to its increasing prevalence, breast cancer has become a serious public health problem. In addition to the models used to identify individuals at risk, the search for fast and accurate tools has continued for years. In our study, we aimed to examine the correlation of mammographic density measurement and serum Mullerian-inhibiting substance (MIS) levels with an effective model such as Gail. Of the women whose serum MIS levels were measured in the last 1 year, 214 participants who applied for routine breast examination were included in the study. The age range was between 40 and 60. Exclusion criteria were determined as pathological mammographic findings, active breast symptom, and thoracic radiotherapy history. Mammographic density measurement (PD) was performed with the artificial intelligence-based Deep-LIBRA software. The relationship of these two parameters with the lifetime risk of developing breast cancer was examined. The correlation between PD and GRP was remarkable (p < 0.01 cc0.35). A positive correlation was observed between serum MIS levels and increased breast cancer, but it was not possible to prove this statistically (p 0.056). It was thought that this situation was caused by perimenopausal patients. Because when the menopause group was excluded, the correlation between MIS levels and GRP decreased (p 0.12 cc0.17). PD measurement can be considered as a promising method for the determination of individuals at risk for breast cancer in a large group of patients, but we think that serum MIS levels are not suitable for risk assessment in perimenopausal patients. |
36,229,578 | Corynoxine suppresses pancreatic cancer growth primarily via ROS-p38 mediated cytostatic effects. | Pancreatic cancer is among the most common malignant tumours, and effective therapeutic strategies are still lacking. While Corynoxine (Cory) can induce autophagy in neuronal cells, it remains unclear whether Cory has anti-tumour activities against pancreatic cancer. Two pancreatic cancer cell lines, Patu-8988 and Panc-1, were used. Effects of Cory were evaluated by cell viability analysis, EdU staining, TUNEL assay, colony formation assay, and flow cytometry. Quantitative PCR and Western blot were performed to analyse mRNA and protein levels, respectively. In vivo anti-tumour efficacy of Cory was determined by a xenograft model. Cory treatment inhibited cell proliferation, induced endoplasmic reticulum (ER) stress, and triggered apoptosis in the pancreatic cancer cell lines. CHOP knockdown-mediated inhibition of ER stress alleviated the Cory-induced apoptosis but showed a limited effect on cell viability. Cory induced cell death partially via promoting reactive oxygen species (ROS) production and activating p38 signalling. Pretreatment with ROS scavenger N-acetylcysteine and p38 inhibitor SB203580 relieved the Cory-induced inhibition on cell growth. Cory remarkably blocked pancreatic tumour growth in vivo. Cory exerts an anti-tumour effect on pancreatic cancer primarily via ROS-p38-mediated cytostatic effects. Cory may serve as a promising therapeutic agent for pancreatic cancer. |
36,229,542 | Low TINAGL1 expression is a marker for poor prognosis in breast cancer. | Tubulointerstitial nephritis antigen-like 1 (TINAGL1) was reported to suppress tumor metastasis and growth in triple-negative (TN) breast cancer. We aimed to determine the associations of TINAGL1 expression with clinicopathological factors and prognosis in breast cancer patients with long-term follow-up. A total of 599 consecutive primary invasive breast cancer patients with available tissue specimens from surgery in our hospital were included in the study. TINAGL1 mRNA expression was examined in all 599 tissue specimens using a TaqMan real-time PCR system. TINAGL1 protein expression was further examined in 299 patients with available tissue specimens for immunohistochemical staining. Survival analyses were performed using the Kaplan-Meier method and Cox proportional hazards models. The median follow-up period was 12.0 years. In the total patients, low TINAGL1 mRNA expression was associated with significantly shorter disease-free survival (DFS) and overall survival than high expression (P 0.003 and P 0.01, respectively). Furthermore, hormone receptor-positivehuman epidermal growth factor receptor 2-negative breast cancer patients with low TINAGL1 mRNA expression had a worse prognosis. Multivariate analysis identified low TINAGL1 mRNA expression, combined with lymph node positivity, as an independent poor prognostic factor for DFS in invasive breast cancer patients (HR 1.41 95% CI 1.02-1.96 P 0.036). TINAGL1 mRNA expression also varied with menopausal status, with low TINAGL1 mRNA expression being positively associated with poor prognosis in premenopausal patients, but not in postmenopausal patients. Our findings demonstrate that TINAGL1 may be a promising candidate biomarker and therapeutic target in breast cancer patients. |
36,229,503 | Longitudinal bioluminescence imaging to monitor breast tumor growth and treatment response using the chick chorioallantoic membrane model. | The development of successful treatment regimens for breast cancer requires strong pre-clinical data generated in physiologically relevant pre-clinical models. Here we report the development of the chick embryo chorioallantoic membrane (CAM) model to study tumor growth and angiogenesis using breast cancer cell lines. MDA-MB-231 and MCF7 tumor cell lines were engrafted onto the chick embryo CAM to study tumor growth and treatment response. Tumor growth was evaluated through bioluminescence imaging and a significant increase in tumor size and vascularization was found over a 9-day period. We then evaluated the impact of anti-angiogenic drugs, axitinib and bevacizumab, on tumor growth and angiogenesis. Drug treatment significantly reduced tumor vascularization and size. Overall, our findings demonstrate that the chick embryo CAM is a clinically relevant model to monitor therapeutic response in breast cancer and can be used as a platform for drug screening to evaluate not only gross changes in tumor burden but physiological processes such as angiogenesis. |
36,229,490 | A new obligate CXCL4-CXCL12 heterodimer for studying chemokine heterodimer activities and mechanisms. | Chemokines form a family of proteins with critical roles in many biological processes in health and disease conditions, including cardiovascular, autoimmune diseases, infections, and cancer. Many chemokines engage in heterophilic interactions to form heterodimers, leading to synergistic activity enhancement or reduction dependent on the nature of heterodimer-forming chemokines. In mixtures, different chemokine species with diverse activities coexist in dynamic equilibrium, leading to the observation of their combined response in biological assays. To overcome this problem, we produced a non-dissociating CXCL4-CXCL12 chemokine heterodimer OHD |
36,229,362 | Irregular sleep and all-cause mortality A large prospective cohort study. | Previous studies using objective parameters have shown that irregular sleep is associated with the disease incidence, progression, or mortality. This study aimed to determine the association between subjective sleep duration and sleep regularity, with mortality in a large population. Participants were from the Japan Multi-Institutional Collaborative Cohort study. We obtained information from each participant on sleep duration, sleep regularity, and demographics and overall lifestyle using self-administered questionnaires. We defined sleep regularity according to participants subjective assessment of sleepwake time regularity. Participants (n 81,382, mean age 58.1 ± 9.1years, males 44.2%) were classified into 6 groups according to sleep duration and sleep regularity. Hazard ratios (HR) for time-to-event of death were calculated using the Cox proportional hazards model. The mean follow-up period was 9.1 years and the mean sleep duration was 6.6 hday. Irregular sleep significantly increased the risk of all-cause mortality in all models compared with regular sleep (HR 1.30, 95% confidence interval CI, 1.18-1.44), regardless of sleep duration. Multivariable analysis of the 6 groups by sleep pattern (sleep regularity and duration) showed irregular sleep and sleep durations of <6 hday, 6 to <8 hday, or ≥8 hday were associated with a 1.2-1.5-fold increases in mortality, compared to regular sleep and sleep duration of 6 to <8 hday. Our study shows an association between sleep irregularity and all-cause mortality in a large Japanese population. Our findings provide further confirmation of the need to consider not only sleep duration, but also the regularity aspect of sleep schedules. |
36,229,337 | Tryptophan and Kynurenine Pathway Metabolites and Psychoneurological Symptoms Among Breast Cancer Survivors. | Among breast cancer survivors, pain, fatigue, depression, anxiety, and sleep disturbance are common psychoneurological symptoms that cluster together. Inflammation-induced activation of the tryptophan-kynurenine metabolomic pathway may play an important role in these symptoms. This study investigated the relationship between the metabolites involved in the tryptophan-kynurenine pathway and psychoneurological symptoms among breast cancer survivors. Cross-sectional study. Participants were recruited at the oncology clinic at the University of Illinois Hospital Health Sciences System. 79 breast cancer survivors after major cancer treatment. We assessed psychoneurological symptoms with the PROMIS-29 and collected metabolites from fasting blood among breast cancer survivors after major cancer treatment, then analyzed four major metabolites involved in the tryptophankynurenine pathway (tryptophan, kynurenine, kynurenic acid, and quinolinic acid). Latent profile analysis identified subgroups based on the five psychoneurological symptoms. Mann-Whitney U tests and multivariable logistic regression compared targeted metabolites between subgroups. We identified two distinct symptom subgroups (low, 81% high, 19%). Compared with participants in the low symptom subgroup, patients in the high symptom subgroup had higher BMI (p .024) and were currently using antidepressants (p .008). Using multivariable analysis, lower tryptophan levels (p .019) and higher kynureninetryptophan ratio (p .028) were associated with increased risk of being in the high symptom subgroup after adjusting for BMI and antidepressant status. The tryptophan-kynurenine pathway and impaired tryptophan availability may contribute to the development of psychoneurological symptoms. |
36,229,335 | The Impact of Chemotherapy Prescription on Long-Term Survival Outcomes in Early-Stage Invasive Lobular Carcinoma - A Systematic Review and Meta-Analysis. | Invasive lobular carcinoma (ILCs) are typically endocrine responsive breast cancers which respond poorly to chemotherapy. The long-term survival advantage of prescribing chemotherapy in such cases remains unclear. To perform a systematic review and meta-analysis assessing, the impact of prescribing chemotherapy in such patients on long-term disease-free (DFS) and overall (OS) survival outcomes. A systematic review and meta-analysis was performed in accordance with the PRISMA guidelines. Ten-year DFS and OS were pooled as odds ratios (ORs) with 95% confidence intervals (CI) using the Mantel-Haenszel method. Time-to-effect modelling was performed using the generic inverse variance method. Overall, 9 studies including 28,218 patients were included. The mean follow-up was 74 months (range 0-150 months) and mean age was 60 years (range 22-90 years). Of these, 34.7% received chemotherapy (9,79728,218) and 66.3% did not receive chemotherapy (18,42128,218). Chemotherapy prescription failed to improve 10-year DFS (OR 0.89, 95% CI 0.65-1.23) and OS (OR 0.92, 95% CI 0.72-1.18). When using time-to-effect modelling, chemotherapy prescription failed to improve DFS (hazard ratio (HR) 1.01, 95% CI 0.78-1.31) and OS (HR 1.07, 95% CI 0.89-1.27, I This meta-analysis illustrates no long-term survival advantage associated with chemotherapy prescription in the setting of early-stage ILC. In the absence of well-designed, prospective clinical trials evaluating the impact of chemotherapy on long-term outcomes in ILC, these results should be considered by the multidisciplinary team when deciding on the value of systemic chemotherapy prescription in ILC. |
36,229,268 | Impact of the COVID-19 pandemic on breast cancer management Experience of a French Comprehensive Cancer Center. | The COVID-19 pandemic had a profound impact on health-care systems and reduced access to care. This study assays the mid-term effects of the COVID-19 pandemic on breast cancer management over a 2-year-period in a single French Comprehensive Cancer Center. We performed, in a French comprehensive cancer center, an observational study including all patients with newly diagnosed breast cancer between 2019 and 2021. We collected the number of first consultations for breast cancer, the number of breast and axillary surgeries, pTNM and ypTNM cancer staging, the therapeutic sequence (surgery or neoadjuvant chemotherapy as a primary treatment), patients age and their place of residence. In total, 14,772 patients had a first consultation for breast cancer. Among these 9058 breast and axillary surgeries were performed, 1798 patients had neoadjuvant chemotherapy as a primary treatment. During the first COVID-19 lockdown ( March17, 2020-May 10, 2020), we observed a reduction in the number of first consultations for breast cancer and breast cancer surgeries giving respectively a 42.3% and 27% rate of change. Subsequently, we observed a resumption of consultations and surgeries with a slight increase in early 2021 compared to 2019. In addition, we did not find any difference in terms of therapeutic sequence, pTNM and ypTNM stages, age at diagnosis or place of residence between the reference year 2019 and the years 2020 and 2021. Our study shows a decrease in activity during the first lockdown of 2020, then a resumption of activity. These reassuring results only concern patients with breast cancer, and are specific to our institution, whose oncology activity was preserved during the COVID-19 pandemic. La pandémie de COVID-19 a engendré une réorganisation de l’offre de santé, limitant l’accès aux soins. Notre objectif était d’évaluer l’impact à moyen terme de la pandémie sur les cancers du sein pris en charge dans notre institution sur une période de deux ans. Nous avons réalisé une étude observationnelle incluant toutes les patientes avec un nouveau diagnostic de cancer du sein entre 2019 et 2021, prises en charge dans notre centre de lutte contre le cancer . Nous avons recueilli le nombre de premières consultations pour cancer du sein, le nombre de chirurgies, les stades p et ypTNM, la séquence thérapeutique, l’âge et le lieu de résidence des patientes. Sur la période d’étude, 14 772 patientes ont bénéficié d’une première consultation de cancer du sein, 1798 patientes d’une chimiothérapie néoadjuvante et 9058 actes de chirurgie mammaire ou axillaire ont été réalisés. Lors de la première vague épidémique (17 mars 2020–10 mai 2020) le nombre de premières consultations (−42,3 %) et de chirurgies (−27 %) a diminué, puis a légèrement repris début 2021, comparé à 2019. Il n’y a pas eu de différence de séquence thérapeutique, de stades pTNM et ypTNM, d’âge au diagnostic ou de lieu de résidence entre l’année 2019 et la période pandémique. L’activité de cancérologie mammaire a diminué lors du premier confinement, puis a repris. Ces résultats rassurants concernent le cancer du sein, et sont propres à notre institution dont l’activité a été préservée durant la pandémie de COVID-19. |
36,228,963 | Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA12 and high-risk, early breast cancer. | The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA12pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group hazard ratio 0.68 98.5% confidence interval (CI) 0.47-0.97 P 0.009. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Δ 3.4%, 95% CI -0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. With 3.5 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA12pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDFS and DDFS with no new safety signals. |
36,228,865 | Expression of matrix metalloproteinases and their association with clinical characteristics of solid tumors. | Matrix metalloproteinases (MMPs) are a group of zinc-dependent enzyme families that play an important role in regulating human physiological as well as pathological processes, especially in malignant tumors. Numerous experimental studies have shown that MMPs are not only involved in the occurrence and development of solid tumors but also play a key role in the staging and grading of tumors. The specific processes by which MMPs are involved in tumor cell invasion and metastasis mainly include degradation of the extracellular matrix, regulation of gene polymorphism, promotion of epithelial-mesenchymal transformation, and induction of adhesion molecule expression. The correlated expression of MMPs in different solid tumors provides a basis for tumor markers, tumor prognosis, and drug targets. In this review, the function, classification, and nomenclature of MMPs will be summarized, and the relevant expression of MMPs in solid tumors, as well as the clinical survival rate and general prognosis associated with MMPs, will be elaborated to provide useful information on which to base the search for new targets for tumor therapy. |
36,228,736 | EMT status of circulating breast cancer cells and impact of fluidic shear stress. | Circulating tumor cells (CTCs) play a vital role in the metastasis and recurrence of breast cancer. CTCs are highly heterogeneous at the stage of Epithelial-to-Mesenchymal Transition (EMT), but the phenotypic and biological characteristics in different EMT stages remain poorly defined. We conducted an orthotopic mouse (4T1) model of breast cancer to isolate CTCs and identified two phenotypes of CTCs intermediate EM and mesenchymal CTCs. MTT, Colony formation, Transwell migration and invasion assays were utilized to examined cell proliferation, colony forming, migration and invasion ability. Both the intermediate EM and mesenchymal CTCs exhibited lower rates of proliferation, colony formation and invasion, as compared to primary tumor cells. The mesenchymal CTCs had a higher rate of invasion but lower rates of proliferation and colony formation than the intermediate EM CTCs. They also exhibited lower rates of growth and metastasis than the primary tumor cells in vivo, but the mesenchymal CTCs had a higher rate of metastasis than the intermediate EM CTCs. Fluid shear stress induced the EMT transition of CTCs. The comprehensive analysis of CTCs proteomics discovered proteins that differentially expressed in the two types of CTCs and their primary tumor cells. |
36,228,719 | Protein tyrosine kinase 6 regulates activation of SRC kinase. | Expression of Protein tyrosine kinase 6 (PTK6) is upregulated in several human solid tumors, and it has oncogenic roles in prostate and breast cancer. PTK6 and SRC kinase are distantly related, share many substrates, and often regulate the same signaling pathways, but whether they interact to regulate signaling is not well understood. We characterized crosstalk between PTK6 and SRC and show that PTK6 can directly phosphorylate SRC to promote its activation. Stable knockdown of PTK6 in multiple cancer cell lines leads to decreased activating phosphorylation of SRC. We show that coexpression of kinase-dead SRC and active PTK6 in mouse embryonic fibroblasts lacking Src, Yes, and Fyn results in activating phosphorylation of SRC. However, there is no reciprocal effect, because active SRC does not promote activating phosphorylation of PTK6. Overexpression of active PTK6 maintained activation of epidermal growth factor receptor (EGFR), AKT, and FAK, but not SHP2 and ERK12 in cells with knockdown of SRC. Both PTK6 and SRC are regulated by EGFR, and its inhibition with erlotinib downregulated PTK6 and to a lesser degree SRC activation in LNCaP cells that overexpress active PTK6. Erlotinib treatment also led to AKT inhibition, but overexpression of active PTK6 prevented this. Our data demonstrate overlapping and unique functions for PTK6 and SRC. Finally, we show that PTK6 and SRC are coexpressed in subsets of human prostate and breast cancer cells, and active PTK6 and active SRC colocalize in prostate cancer, supporting a role for PTK6 in promoting SRC activity in cancer. |
36,228,705 | Cannabidiolic acid activates the expression of the PPARβδ target genes in MDA-MB-231 cells. | Cannabidiolic acid (CBDA) can activate peroxisome proliferator-activated receptor-α (PPARα) and PPARγ. Whether CBDA can activate PPARβδ has not been examined sufficiently to date. Since previous studies showed that triple-negative breast cancer cells respond to activation of PPARβδ, the present study examined the effect of CBDA in MDA-MB-231 cells and compared the activities of CBDA with known PPARβδ agonistsantagonists. Expression of the PPARβδ target genes angiopoietin-like 4 (ANGPTL4) and adipocyte differentiation-related protein (ADRP) was increased by CBDA. Interestingly, ligand activation of PPARβδ with GW501516 caused an increase in expression of both ANGPTL4 and ADRP, but the magnitude of this effect was markedly increased when co-treated with CBDA. Specificity of these effects were confirmed by showing that CBDA-induced expression of ANGPTL4 and ADRP is mitigated in the presence of either a PPARβδ antagonist or an inverse agonist. Results from these studies suggest that CBDA can synergize with PPARβδ and might interact with endogenous agonists that modulate PPARβδ function. |
36,228,653 | Impact of Postmastectomy Radiation Therapy on Breast Cancer Patients According to Pathologic Nodal Status after Modern Neoadjuvant Chemotherapy. | The utility of postmastectomy radiation therapy (PMRT) for breast cancer patients after neoadjuvant chemotherapy (NAC) is highly controversial. This study evaluated the impact of PMRT according to pathologic nodal status after modern NAC. We retrospectively reviewed 682 patients with clinical stage II-III breast cancer who underwent NAC and mastectomy from 2013 to 2017. In total, 596 (87.4%) patients received PMRT, and 86 (12.6%) did not. We investigated the relationships among locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), overall survival (OS), and various prognostic factors. Subgroup analyses were also performed to identify patients who may benefit from PMRT. The median follow-up duration was 67 months. In ypN patients (n368, 51.2%), PMRT showed significant benefits in terms of LRRFS, DFS, and OS (all p < 0.001). In multivariate analyses, histologic grade (HG) III (p0.002), lymphovascular invasion (LVI) (p0.045), and ypN2-3 (p0.02) were significant risk factors for poor LRRFS. In ypN1 patients with more than two prognostic factors among luminalHER2-negative subtype, HG I-II, and absence of LVI, PMRT had no significant effect on LRRFS (p0.18). In ypN0 patients (n351, 48.8%), PMRT was not significantly associated with LRRFS, DFS, or OS. However, PMRT showed better LRRFS in triple-negative breast cancer (TNBC) patients (p0.03). PMRT had a major impact on treatment outcomes in patients with residual lymph nodes following NAC and mastectomy. Among ypN0 patients, PMRT may be beneficial only for those with TNBC. |
36,228,632 | Performance evaluation of digital breast tomosynthesis systems physical methods and experimental data. | Digital breast tomosynthesis (DBT) has become a well-established breast imaging technique, whose performance has been investigated in many clinical studies, including a number of prospective clinical trials. Results from these studies generally point to non-inferiority in terms of microcalcification detection and superior mass-lesion detection for DBT imaging compared to digital mammography (DM). This modality has become an essential tool in the clinic for assessment and ad-hoc screening but is not yet implemented in most breast screening programmes at a state or national level. While evidence on the clinical utility of DBT has been accumulating, there has also been progress in the development of methods for technical performance assessment and quality control of these imaging systems. DBT is a relatively complicated pseudo-3D modality whose technical assessment poses a number of difficulties. This paper reviews methods for the technical performance assessment of DBT devices, starting at the component level in part one and leading up to discussion of system evaluation with physical test objects in part two. We provide some historical and basic theoretical perspective, often starting from methods developed for DM imaging. Data from a multi-vendor comparison are also included, acquired under the medical physics quality control protocol developed by EUREF and currently being consolidated by a European Federation of Organisations for Medical Physics working group. These data and associated methods can serve as a reference for the development of reference data and provide some context for clinical studies. |
36,228,577 | Influence of multimodal treatment on restactivity and autonomic regulation in breast cancer patients with cancer related fatigue - results of a tri-center trial with a comprehensive cohort design. | Breast cancer patients with cancer-related fatigue (BC-CRF) often have lower physical activity. To investigate how this could be improved we evaluated a multimodal treatment (MT) and a combination of MT with aerobic training (CT) were and compared these with aerobic training (AT) regarding restactivity rhythm and state autonomic regulation (State aR). In this pragmatic comprehensive cohort design study the explorative analysis focused on actigraphy and State aR including the restactivity regulation subscale (State aR-RA) which were assessed at baseline (T0), after ten weeks of intervention (T1) and State aR additionally six months later (T2). General linear modelling including propensity scores. 65 BC-CRF were randomised and 61 allocated by preference to the treatment arms. 105 patients started the intervention. At T1 State aR-RA improved the most in MT (3.49, CI 2.42 4.55) compared to AT (1.59, CI 0.13 3.06 and CT (1.68, CI 0.83 2.52) showing superiority of MT to AT (p0.048). At T2 MT was sustainably superior to AT regarding State aR-RA (3.61, CI 2.38 4.83 p<0.01) and State aR also showed superiority of MT to AT (p0.006). AT T1 24-hour activity was higher in MT compared to AT (p0.029). MT was superior to AT regarding State aR total score after six months, State aR-RA after 10 weeks and after six months. Actigraphically measured total activity also improved after 10 weeks. |
36,228,497 | MiR-135a-5p suppresses breast cancer cell proliferation, migration, and invasion by regulating BAG3. | MicroRNAs (miRNAs) are involved in the progression of diverse human cancers. This work aimed to delve into how microRNA-135a-5p (miR-135a-5p) affects the biological behaviors of Breast Cancer (BC) cells. Gene Expression Omnibus (GEO) datasets were used to analyze the expression differences of miR-135a-5p in cancer tissues of BC patients. Quantitative real-time PCR and western blot were conducted to detect miR-135a-5p and Bcl-2 Associated Athanogene (BAG3) expression levels in BC tissues and cells, respectively. The proliferation, migration, invasion, and cell cycle of BC cells were detected by cell counting kit-8 assay, BrdU assay, wound healing assay, transwell assay, and flow cytometry. The targeted relationship between miR-135a-5p and BAG3 mRNA 3UTR predicted by bioinformatics was further testified by a dual-luciferase reporter gene assay. Pearsons correlation analysis was adopted to analyze the correlation between miR-135a-5p expression and BAG3 expression. The downstream pathways of BAG3 were analyzed by the LinkedOmics database. MiR-135a-5p was significantly down-regulated and BAG3 expression was significantly raised in BC tissues. MiR-135a-5p overexpression repressed the viability, migration and invasion of BC cells, and blocked cell cycle progression in G0G1 phase while inhibiting miR-135a-5p worked oppositely. BAG3 was verified as a target of miR-135a-5p. Overexpression of BAG3 reversed the impacts of miR-135a-5p on the malignant biological behaviors of BC cells. The high expression of BAG3 was associated with the activation of the cell cycle, mTOR and TGF-β signaling pathways. MiR-135a-5p regulates BAG3 to repress the growth, migration, invasion, and cell cycle progression of BC cells. |
36,228,488 | Enhancing the photoinduced via a novel nano-combination of terbium oxide and nickel oxide on graphene oxide surface Cytotoxicity and water treatment. | The target is a novel nano-combination membrane (NCM) via Terbium oxide nanoparticles (Tb |
36,228,406 | The effect of an evidence-based Tai chi intervention on the fatigue-sleep disturbance-depression symptom cluster in breast cancer patients A preliminary randomised controlled trial. | To explore the potential effects of Tai chi on the fatigue-sleep disturbance-depression symptom cluster (FSDSC) among breast cancer (BC) patients. This study was conducted as a preliminary randomized controlled trial among 72 BC patients (36 Tai chi and 36 control participants). All the participants were provided with routine care, while participants in the Tai chi group received an additional 8-week Tai chi intervention. Participants fatigue, sleep disturbance and depression were assessed by the Brief Fatigue Inventory, the Pittsburgh Sleep Quality Index, and the Hospital Anxiety and Depression Scale-Depression. Participants quality of life (QoL) was assessed by the Functional Assessment of Cancer Therapy-Breast. Both covariates-unadjusted and adjusted GEE models were run to assess the effects of Tai chi intervention on the FSDSC and QoL and the relevant impacts of the covariates. Sixty-nine participants completed this study. In the unadjusted GEE model, compared with the control group and baseline, participants in the Tai chi group showed significant reductions in fatigue (p < 0.001), sleep disturbance (p < 0.001) and depression (p 0.006), as well as a significant improvement in QoL (p 0.032) at immediately post-intervention and four-week follow-up. The positive regression coefficients of the adjusted GEE model showed fatigue, sleep disturbance and depression can have impacts on each other (all at p < 0.05). Tai chi as an adjuvant intervention to routine care could relieve the symptom cluster of fatigue, sleep disturbance and depression and improve QoL among BC patients. |
36,228,405 | Psychological group intervention to support parenting Qualitative study about needs and preferences of mothers with breast cancer. | Parental worries and parenting stress can increase when a mother receives a breast cancer diagnosis. This study presents the findings of needs and preferences of mothers with breast cancer to inform the development of a group intervention program for mothers with breast cancer and other alternatives of support. Using qualitative data from eighteen Portuguese women with at least one minor child when they received a breast cancer diagnosis, and content analysis on three focus groups transcripts, we uncover the participants parenting needs and their perceptions of the potential benefits and the formal aspects of a group intervention. Mothers revealed that they need support on several parenting-related issues (e.g., communicating with the children about the mothers diagnosis, dealing with childrens responses and difficult questions). They provided information about the potential benefits of group intervention and preferences regarding intervention content, sessions structure, frequency, location, and timing. Some participants also suggested other types of support, such as online information and individual psychological support. The development of an intervention informed by the patients needs and preferences can contribute to increasing its feasibility and efficacy. The findings indicated the specific parenting needs of Portuguese mothers with breast cancer, and it offered health professionals some important clues on how to support other family members. |
36,228,375 | Targeting hypoxia-inducible factor-1alpha A new strategy for triple-negative breast cancer therapy. | Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is highly aggressive and hypoxic compared with other subtypes. The role of hypoxia inducible factor 1α (HIF-1α) as a key hypoxic transcription factor in oncogenic processes has been extensively studied. Recently, it has been shown that HIF-1α regulates the complex biological processes of TNBC, such as glycolysis, angiogenesis, invasion and metastasis, breast cancer stem cells (BCSCs) enrichment, and immune escape, to promote TNBC survival and development through the activation of downstream target genes. In addition, inflammatory mediators, oxygen levels, noncoding RNAs, complex signaling regulatory networks, epigenetic regulators are involved in the upstream regulatory expression of HIF-1α. However, further studies are needed to determine the potential and future directions of targeting HIF-1α in TNBC. This article discusses the expression of the HIF-1α transcription factor in TNBC. We also explored the mechanism by which HIF-1α drives TNBC progression. The potential significance of targeting HIF-1α for immunotherapy, chemotherapy, anti-angiogenic therapy, and photodynamic therapy is discussed. The intrinsic mechanism, existing problems and future directions of targeting HIF-1α are also studied. |
36,228,339 | A Review of Immune Checkpoint Blockade for the General Surgeon. | The immune system is a complex and interconnected system that has evolved to protect its host from foreign pathogens. CD8 |
36,228,215 | Cytotoxicity, antinociceptive and gastroproiltective potential of the Abuta selloana Eichler a fruit plant from Catarinense flora, Brazil. | This study evaluated some biological activities of extracts from Abuta selloana. The gastroprotective potential was determined against ethanolHCl- and indomethacin-induced gastric ulcers, whereas the antinociceptive effect was evaluated by acetic acid-induced abdominal contortions in mice. The cytotoxicity activity was measured against human cancer cell lines U251 (glioma), MCF-7 (breast cancer) and NCI-H460 (lung cancer). The radical scavenger potential was verified and preliminary phytochemical analyses were performed. The phytochemical screening revealed higher levels of phenolic compounds in all extracts. Moreover, the methanolic extract from pulp fruit (MEPu), peel fruit (MEPe), branches (MEB) and leaves (MEL) scavenged the DPPH radical at 100 µgmL. Besides, only MEL presented GI50 < 30 µgmL in all tested cells. Besides, MEPu, MEPe, MEB or MEL at 10 mgkg (i.p) reduced the abdominal contortions at 47.22%, 63.31%, 84.59% and 37.76%, respectively. The MEPu, MEPe, MEB and MEL reduced the ethanolHCl- and indomethacin- induced ulcer at 250 mgkg (p.o). In conclusion, A. selloana had interesting biological activities presenting the leaves as a promising source for compounds with cytotoxic potential, however, further studies should be performed to confirm its antitumoral activity. Besides, the whole plant can be an important source of bioactive compounds associated with gastroprotective and antinociceptive properties. |
36,228,177 | A Pragmatic Cluster-Randomized Trial of a Standing Order Entry Intervention for Colony-Stimulating Factor Use Among Patients at Intermediate Risk for Febrile Neutropenia. | Primary prophylactic colony-stimulating factors (PP-CSFs) are prescribed to reduce febrile neutropenia (FN) but their benefit for intermediate FN risk regimens is uncertain. Within a pragmatic, randomized trial of a standing order entry (SOE) PP-CSF intervention, we conducted a substudy to evaluate the effectiveness of SOE for patients receiving intermediate-risk regimens. TrACER was a cluster randomized trial where practices were randomized to usual care or a guideline-based SOE intervention. In the primary study, sites were randomized 31 to SOE of automated PP-CSF orders for high FN risk regimens and alerts against PP-CSF use for low-risk regimens versus usual care. A secondary 11 randomization assigned 24 intervention sites to either SOE to prescribe or an alert to not prescribe PP-CSF for intermediate-risk regimens. Clinicians were allowed to over-ride the SOE. Patients with breast, colorectal, or non-small-cell lung cancer were enrolled. Mixed-effect logistic regression models were used to test differences between randomized sites. Between January 2016 and April 2020, 846 eligible patients receiving intermediate-risk regimens were registered to either SOE to prescribe (12 sites n 542) or an alert to not prescribe PP-CSF (12 sites n 304). Rates of PP-CSF use were higher among sites randomized to SOE (37.1% Although implementation of a SOE intervention for PP-CSF significantly increased PP-CSF use among patients receiving first-line intermediate-risk regimens, FN rates were low and did not differ between arms. Although this guideline-informed SOE influenced prescribing, the results suggest that neither SOE nor PP-CSF provides sufficient benefit to justify their use for all patients receiving first-line intermediate-risk regimens. |
36,228,112 | Phase I Dose Escalation Study of Topical Bexarotene in Women at High Risk for Breast Cancer. | Bexarotene is a rexinoid that has been shown to prevent mammary tumors in mouse models but oral dosing has toxicities. This phase I study evaluates topical bexarotene, as a potential chemoprevention agent, for safety and toxicity in high-risk women for breast cancer. |
36,228,003 | CNAViz An interactive webtool for user-guided segmentation of tumor DNA sequencing data. | Copy-number aberrations (CNAs) are genetic alterations that amplify or delete the number of copies of large genomic segments. Although they are ubiquitous in cancer and, thus, a critical area of current cancer research, CNA identification from DNA sequencing data is challenging because it requires partitioning of the genome into complex segments with the same copy-number states that may not be contiguous. Existing segmentation algorithms address these challenges either by leveraging the local information among neighboring genomic regions, or by globally grouping genomic regions that are affected by similar CNAs across the entire genome. However, both approaches have limitations overclustering in the case of local segmentation, or the omission of clusters corresponding to focal CNAs in the case of global segmentation. Importantly, inaccurate segmentation will lead to inaccurate identification of CNAs. For this reason, most pan-cancer research studies rely on manual procedures of quality control and anomaly correction. To improve copy-number segmentation, we introduce CNAViz, a web-based tool that enables the user to simultaneously perform local and global segmentation, thus overcoming the limitations of each approach. Using simulated data, we demonstrate that by several metrics, CNAViz allows the user to obtain more accurate segmentation relative to existing local and global segmentation methods. Moreover, we analyze six bulk DNA sequencing samples from three breast cancer patients. By validating with parallel single-cell DNA sequencing data from the same samples, we show that by using CNAViz, our user was able to obtain more accurate segmentation and improved accuracy in downstream copy-number calling. |
36,227,931 | Physical exercise during neoadjuvant chemotherapy for breast cancer as a mean to increase pathological complete response rates Trial protocol of the randomized Neo-ACT trial. | In early breast cancer, neoadjuvant chemotherapy (NACT) is increasingly used. The proof of efficacy is pathologically complete response (pCR), i.e. the absence of invasive tumour in breast and lymph nodes at surgery. Today, pCR is a common endpoint in pharmaceutical trials since it is significantly associated with survival especially in triple-negative and HER2-positive subtypes. Apart from the mitigation of treatment-related toxicity and symptoms, physical exercise mediates anti-tumoral systemic effects associated with tumour regression in preclinical and clinical models. The aim of Neo-ACT is to test the hypothesis that physical exercise can improve pCR rates in breast cancer patients receiving NACT. The Neo-ACT trial is a prospective clinical trial, randomising T1-3N0-2 breast cancer patients planned for NACT to either a home-based physical exercise intervention supported by a mobile application or routine care. The primary endpoint is pCR secondary endpoints are patient-reported quality of life, toxicity-related outcomes, and oncological outcomes such as Residual Cancer Burden, objective radiological tumour response, as well as overall, breast cancer-specific and disease-free survival at 2, 5 and 10 years. The intervention consists of a combination of high-intensity interval and resistance training of progressing intensity, and includes at least 150 min of moderate to vigorous physical activity per week, inclusive of two weekly 60-min exercise sessions. In order to show an improvement in pCR of 10%, a total of 712 participants need to be included in the analysis. The Neo-ACT has been registered at clinicaltrials.gov on January 11, 2022 (NCT05184582). If Neo-ACT can prove the oncological efficacy of physical exercise, implementation of training programmes into NACT schedules will be pursued. The use of a digitally led exercise intervention aims to test the potential of such a strategy for use in rural areas and areas of limited resources. |
36,227,794 | Suicide and women living with and beyond a breast cancer diagnosis. | Early diagnosis and intervention, and the use of targeted cancer treatments, have significantly reduced mortality from breast cancer. Emotional distress following a diagnosis of cancer is a normal and anticipated, but it may manifest in some individuals at some point as a level of anxiety or depression that significantly affects quality of life and coping. In extreme cases, these feelings can move from physical symptoms of low energy and an inability to complete basic tasks to despair and hopelessness. Confronting a cancer diagnosis is a life-changing experience, bringing a sense of vulnerability. This may create or precipitate a crisis that threatens to overwhelm a person, resulting in a negative impact on established coping mechanisms. There appears to be a paucity of literature on suicide or suicide attempts by people living with and beyond a cancer diagnosis. A literature search identified 19 papers on suicide and or suicide ideation in patients who had had a cancer diagnosis, which were included in the review. Two clear themes emerged from the literature that a cancer diagnosis with or without pre-existing mental health comorbidities is a risk factor for suicide and that there is a significant incidence and prevalence of anxiety and depression in cancer patient populations. The literature identifies multiple variables that impact on prevalence of mental health disorders after a breast cancer diagnosis. Despite this, there appears to be a lack of guidance at national level for screening for mental health comorbidities in patients with a cancer diagnosis. |
36,227,691 | The interferon-inducible protein viperin controls cancer metabolic reprogramming to enhance cancer progression. | Metabolic reprogramming is an important cancer hallmark. However, the mechanisms driving metabolic phenotypes of cancer cells are unclear. Here, we show that the interferon-inducible (IFN-inducible) protein viperin drove metabolic alteration in cancer cells. Viperin expression was observed in various types of cancer and was inversely correlated with the survival rates of patients with gastric, lung, breast, renal, pancreatic, or brain cancer. By generating viperin knockdown or stably expressing cancer cells, we showed that viperin, but not a mutant lacking its iron-sulfur cluster-binding motif, increased lipogenesis and glycolysis via inhibition of fatty acid β-oxidation in cancer cells. In the tumor microenvironment, deficiency of fatty acids and oxygen as well as production of IFNs upregulated viperin expression via the PI3KAKTmTORHIF-1α and JAKSTAT pathways. Moreover, viperin was primarily expressed in cancer stem-like cells (CSCs) and functioned to promote metabolic reprogramming and enhance CSC properties, thereby facilitating tumor growth in xenograft mouse models. Collectively, our data indicate that viperin-mediated metabolic alteration drives the metabolic phenotype and progression of cancer. |
36,227,639 | Evaluating the Feasibility of a Digital Therapeutic Program for Patients With Cancer During Active Treatment Pre-Post Interventional Study. | Increasing evidence shows that lifestyle interventions can improve the symptoms, quality of life (QoL), and even overall survival of patients with cancer. Digital therapeutics (DTx) can help implement behavioral modifications and empower patients through education, lifestyle support, and remote symptom monitoring. We aimed to test the feasibility of a DTx program for patients with cancer, as measured by engagement, retention, and acceptability. In addition, we explored the effects of the program on cancer-related QoL. We conducted a 4-week single-arm trial in Iceland, where DTx was delivered through a smartphone app. The intervention consisted of patient education about mindfulness, sleep, stress, and nutrition lifestyle coaching and the completion of daily missions for tracking physical activity and exercise, reporting patient-reported outcomes (PROs), practicing mindfulness, and logging healthy food intake. Information on program engagement and retention, step goal attainment, as well as PROs were collected throughout the study. QoL was measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 at baseline and follow-up. In total, 30 patients with cancer undergoing active therapy were enrolled, and 29 registered in the app (23 female, 18 with breast cancer mean age 52.6, SD 11.5 years). Overall, 97% (2829) of participants were active in 3 of the 4 weeks and completed the pre- and postprogram questionnaires. The weekly active days (median) were 6.8 (IQR 5.8-6.8), and 72% (2129) of participants were active at least 5 days a week. Users interacted with the app on average 7.7 (SD 1.9) times per day. On week 1, all 29 participants used the step counter and logged an average of 20,306 steps 21 (72%) participants reached their step goals of at least 3000 steps per day. On week 4, of the 28 active users, 27 (96%) were still logging their steps, with 19 (68%) reaching their step goals. Of the 28 participants who completed the satisfaction questionnaire, 25 (89%) were likely to recommend the program, 23 (82%) said the program helped them deal with the disease, and 24 (86%) said it helped them remember their medication. QoL assessment showed that the average global health status, functioning, and symptom burden remained stable from baseline to follow-up. In all, 50% (1428) of participants reported less pain, and the average pain score decreased from 31 (SD 20.1) to 22.6 (SD 23.2 P.16). There was no significant change in PROs on the quality of sleep, energy, and stress levels from the first to the last week. The high retention, engagement, and acceptability found in this study demonstrate that multidisciplinary DTx is feasible for patients with cancer. A longer, full-scale randomized controlled trial is currently being planned to evaluate the efficacy of the intervention. |
36,227,603 | Association of Changes in Cancer Therapy Over 3 Decades With Risk of Subsequent Breast Cancer Among Female Childhood Cancer Survivors A Report From the Childhood Cancer Survivor Study (CCSS). | Breast cancer is the most common invasive subsequent malignant disease in childhood cancer survivors, though limited data exist on changes in breast cancer rates as primary cancer treatments have evolved. To quantify the association between temporal changes in cancer treatment over 3 decades and subsequent breast cancer risk. Retrospective cohort study of 5-year cancer survivors diagnosed when younger than 21 years between 1970 and 1999, with follow-up through December 5, 2020. Radiation and chemotherapy dose changes over time. Breast cancer cumulative incidence rates and age-specific standardized incidence ratios (SIRs) compared across treatment decades (1970-1999). Piecewise exponential models estimated invasive breast cancer and ductal carcinoma in situ (DCIS) risk and associations with treatment exposures, adjusted for age at childhood cancer diagnosis and attained age. Among 11 550 female survivors (median age, 34.2 years range 5.6-66.8 years), 489 developed 583 breast cancers 427 invasive, 156 DCIS. Cumulative incidence was 8.1% (95% CI, 7.3%-9.0%) by age 45 years. An increased breast cancer risk (SIR, 6.6 95% CI, 6.1-7.2) was observed for survivors compared with the age-sex-calendar-year-matched general population. Changes in therapy by decade included reduced rates of chest (34% in the 1970s, 22% in the 1980s, and 17% in the 1990s) and pelvic radiotherapy (26%, 17%, and 13% respectively) and increased rates of anthracycline chemotherapy exposures (30%, 51%, and 64%, respectively). Adjusting for age and age at diagnosis, the invasive breast cancer rate decreased 18% every 5 years of primary cancer diagnosis era (rate ratio RR, 0.82 95% CI, 0.74-0.90). When accounting for chest radiotherapy exposure, the decline attenuated to an 11% decrease every 5 years (RR, 0.89 95% CI, 0.81-0.99). When additionally adjusted for anthracycline dose and pelvic radiotherapy, the decline every 5 years increased to 14% (RR, 0.86 95% CI, 0.77-0.96). Although SIRs of DCIS generally increased over time, there were no statistically significant changes in incidence. Invasive breast cancer rates in childhood cancer survivors have declined with time, especially in those younger than 40 years. This appears largely associated with the reduced use of chest radiation therapy, but was tempered by concurrent changes in other therapies. |
36,227,596 | Factors Associated With Patients Not Receiving Oral Anticancer Drugs. | Oral anticancer drugs (OACDs) are increasingly prescribed for cancer treatment and require significant coordination of care. Retrospective studies suggest that 10% to 20% of OACD prescriptions are never received by the patients, but the reasons behind this are poorly understood. To estimate the rate of failure to receive OACD prescriptions among patients with cancer and to examine the underlying reasons for this failure. A prospective cohort study was conducted among patients with cancer who were prescribed a new OACD from January 1, 2018, to December 31, 2019, at an urban academic medical center. Data analysis was conducted between 2021 and 2022. Patient demographic, clinical, and insurance data and OACD delivery dates were collected. The reasons for a failure to receive a prescribed OACD within 3 months were confirmed by manual review of medical records and were classified into 7 categories clinical deterioration, financial access, clinician-directed change in decision-making, patient-directed change in decision-making, transfer of care, loss to follow-up, and unknown or other. A multivariable random-effects model was developed to identify factors associated with failure to receive a prescribed OACD. The cohort included 1024 patients (538 men 53% mean SD age, 66.2 13.9 years 463 non-Hispanic White patients 45%, 140 non-Hispanic Black patients 14%, and 300 Hispanic patients 29%), representing 1197 new OACD prescriptions. Of the 1197 prescriptions, 158 (13%) were categorized as having not been received by the patient. The most common reason for the failure to receive a prescribed OACD was due to patient and clinician decision-making (73 of 158 46%), and 20 cases (13%) in which prescriptions were not received were associated with financial access issues. In multivariable analysis, patients with a nonmetastatic solid malignant neoplasm were significantly less likely to not receive their OACDs than those with a hematologic malignant neoplasm (odds ratio, 0.57 95% CI, 0.33-1.00 P .048). This cohort study of patients prescribed a new OACD found that 13% of prescriptions were not received. The failure to receive a prescribed OACD was most frequently due to a change in clinical decision-making or patient choice. Ultimately, the reasons for the failure to receive a prescribed OACD were multifactorial and may have been appropriate in some cases. |
36,227,588 | 10-year opportunistic mammographic screening scenario in Brazil and its impact on breast cancer early detection a nationwide population-based study. | Mammographic screening has been used to reduce breast cancer mortality worldwide and remains the main modality for the early detection of this disease. Women from low- and middle-income countries still lack access to periodic mammograms and efficient health care. This cross-sectional study aimed to explore opportunistic mammographic coverage in Brazil, while considering the privately insured population and its association with early breast cancer (EBC) detection. Data on population, gross domestic product (GDP), number of mammograms performed under the Sistema Único de Saúde (SUS) public health system or private system, and women diagnosed with early-stage breast cancer from 2010 to 2019 were retrieved from publicly available databases. A total of 39 555 636 mammograms with an average of 3 955 564 ± 395 704 mammograms were obtained per year from 2010 to 2019 in Brazil. Most examinations (58.6%) were performed in the target population (50-69 years old), while 32% were performed in women aged 40-49, and 9.4% were performed in women <40 years or >70 years of age. The 10-year mammogram coverage was 30.6% in the target population and 24.8% in the population aged 40-49 years, with significant variation across states and municipalities. The overall EBC detection rates in Brazil were 30.6% in populations aged 50-70 and 24.8% in those aged 40-50 years. We observed a positive correlation between coverage and EBC detection rate (r 0.68 P 0.0001 (50-70 years) and r 0.75 P < 0.0001 (40-50 years)). According to the GDP, the municipalities with higher GDP per capita had higher mammogram coverage (P < 0.0001). The coverage of mammographic screening for women under the SUS is far below the international guidelines. Additionally, a significant number of mammograms have been performed in non-target populations. This scenario reflects the problematic screening programs in developing countries and reflects low rates of EBC diagnosis. As Brazil is a continental country with heterogeneous socioeconomic indicators, we observed significant variations in the number of mammograms performed by age groups when separated by states and municipalities. Even when considering supplemental health system coverage, municipalities with higher GDP per capita were associated with higher mammogram coverage. |
36,227,551 | Machine Learning Methods for Survival Analysis with Clinical and Transcriptomics Data of Breast Cancer. | Breast cancer is one of the most common cancers in women worldwide, which causes an enormous number of deaths annually. However, early diagnosis of breast cancer can improve survival outcomes enabling simpler and more cost-effective treatments. The recent increase in data availability provides unprecedented opportunities to apply data-driven and machine learning methods to identify early-detection prognostic factors capable of predicting the expected survival and potential sensitivity to treatment of patients, with the final aim of enhancing clinical outcomes. This tutorial presents a protocol for applying machine learning models in survival analysis for both clinical and transcriptomic data. We show that integrating clinical and mRNA expression data is essential to explain the multiple biological processes driving cancer progression. Our results reveal that machine-learning-based models such as random survival forests, gradient boosted survival model, and survival support vector machine can outperform the traditional statistical methods, i.e., Cox proportional hazard model. The highest C-index among the machine learning models was recorded when using survival support vector machine, with a value 0.688, whereas the C-index recorded using the Cox model was 0.677. Shapley Additive Explanation (SHAP) values were also applied to identify the feature importance of the models and their impact on the prediction outcomes. |
36,227,505 | The cancer patients perspective on feasibility of using a fatigue diary and the benefits on self-management results from a longitudinal study. | To evaluate the patients perspective on feasibility of using a fatigue diary and its benefits on self-management. This longitudinal study enrolled 50 cancer patients in routine care. Following baseline (t0) assessment, patients were asked to complete a 7-day fatigue diary and subsequently obtained written diary evaluation. Feasibility, benefits, and fatigue-related attitudes were assessed via self-report 1 (t1) and 4 months (t2) after distributing the diary. Data were analyzed descriptively and using Wilcoxon signed-rank tests. Most patients (94%) completed the diary for 7 days and rated feasibility as high. After diary completion and receiving the evaluation, fewer patients felt helpless in the face of fatigue (t1 21% vs. t0 53%). Additionally, more patients addressed fatigue with their general practitioner (t2 49% vs. t0 36%) and pro-actively searched for information and help (t2 59% vs. t0 38%). The diary enabled a majority of patients to be aware of their fatigue patterns, to plan daily routines accordingly and to take adequate actions against fatigue. The study showed that symptom monitoring via a fatigue diary was considered feasible and enhanced self-management in cancer patients. Thus, fatigue diaries might be a useful measure contributing to an improved fatigue management. The results reinforce guideline recommendations for routine application of fatigue diaries in clinical care. Healthcare professionals should encourage patients to fatigue diary use and provide individually tailored counseling based on diary entries. |
36,227,413 | Adjuvant radiation therapy for older women with early-stage breast cancer a propensity-matched SEER analysis. | The purpose was to evaluate the effect of adjuvant radiation therapy on the survival prognosis of older women with early-stage breast cancer under different surgical treatments. We collected patients from the Surveillance, Epidemiology and End Results (SEER) database. Elderly female patients (≥ 70 years) with stage I-IIB diagnosed with invasive carcinoma in 1988-2017 were included. After propensity score matching (PSM), the prognosis of patients who underwent breast-conserving surgery or mastectomy was calculated separately. The effects of radiotherapy on the survival of three special population groups (breast-conserving surgery T1N0M0 ER positive, mastectomy T3N0M0 and mastectomy T1-2N1M0) were analyzed selectively. Of 106,553 older women with early-stage breast cancer were identified. 48,630 patients had received radiotherapy, while 57,923 patients had not. After PSM, older women undergoing breast-conserving surgery benefited significantly from radiotherapy (both OS and BCSS p < 0.001), for patients with T1N0M0 and ER-positive breast cancer (both OS and BCSS p < 0.001). In the subgroup of T1-2N1M0 breast cancer treated by mastectomy, patients undergoing radiotherapy had a worse survival as well (OS p < 0.001 BCSS p 0.0907). While in the subgroup of T3N0M0 breast cancer treated by mastectomy, survival analyses showed no statistical differences between patients receiving radiation or not (OS p 0.1778, BCSS p 0.6957). This study indicated the clinical effects of radiation on older women who received different surgical treatments. Our study suggested that radiotherapy should be omitted in older women undergoing mastectomy T3N0M0 or T1-2N1M0 and radiotherapy could be considered in women with T1N0M0 ER-positive undergoing breast-conserving surgery. |
36,227,345 | New treatment options for metastatic HER2-low breast cancer Consequences for histopathological diagnosis. | The overexpression of HER2 in breast cancer is a classic example for molecular targeted therapy, and it has been shown that classical anti-HER2 therapeutics were only effective in patients with HER2 overexpressing tumors. Therefore, in recent decades, pathologists have been focused on the reliable identification of HER2 overexpressing tumors. Based on the results of recent clinical trials in metastatic breast cancer with antibody-drug conjugates (ADCs), this diagnostic strategy for evaluation of HER2 is currently changing. It has been shown that the ADC trastuzumab-deruxtecan is effective not only against tumors with classical HER2 overexpression, but also against HER2-low tumors. These clinical trial results lead to a paradigm shift in the treatment of patients whose tumours were previously classified as HER2 negative. In addition to the identification of HER2 (score 3) overexpressing tumors, it is necessary to identify HER2-low expressing tumors (defined as an immunohistochemistry (IHC) score of 1 or IHC2 with negative in situ hybridization).Due to the therapeutic consequences, it is important to quickly adapt the diagnostic workup and reporting to the new requirements. In addition, the new therapeutic options for anti-HER2 therapy lead to new challenges for standardization as well as to new scientific questions for the characterization of tumors with low HER2 expression. Die standardisierte HER2-Bestimmung beim Mammakarzinom und bei anderen Tumoren ist eine wichtige Aufgabe der Pathologie. Ziel der bisherigen Bestimmung war es, zuverlässig diejenigen Tumoren zu identifizieren, die eine Überexpression des HER2-Proteins aufweisen, die in der Regel mit einer Genamplifikation einhergeht. Nur in dieser Gruppe von Tumoren war eine zielgerichtete Anti-HER2-Therapie sinnvoll und erfolgversprechend. Durch neue Substanzen und die Ergebnisse klinischer Studien beim metastasierten Mammakarzinom hat sich dies nun geändert. Es konnte gezeigt werden, dass Trastuzumab-Deruxtecan, ein Konjugat aus einem Anti-HER2-Antikörper und einer zytotoxischen Substanz, auch dann einen Anti-Tumor-Effekt aufweist, wenn nur eine geringe Expression von HER2 im Tumorgewebe vorliegt.Die aktuellen Daten bedeuten einen Paradigmenwechsel für die Behandlung von Patientinnen, deren Tumoren bislang als HER2-negativ eingeordnet wurden. Ziel ist es jetzt, neben den Tumoren mit einer HER2-Überexpression (IHC 3) auch die Tumoren mit einer geringen HER2-Expression (HER2-low, definiert als IHC 1 oder 2ISH-negativ) zuverlässig zu identifizieren. Aufgrund der therapeutischen Konsequenzen ist es wichtig, die diagnostischen Algorithmen und Befundtexte in allen pathologischen Instituten sehr kurzfristig an die neuen Erfordernisse anzupassen. Unabhängig davon ergeben sich neue wissenschaftliche Fragen und Herausforderungen für die Standardisierung, die aktuell bearbeitet werden. |
36,227,171 | Patient voice in metastatic cancer A conceptual analysis. | To analyze the concept of patient voice and discuss implications for clinical care of individuals with metastatic cancer. The diagnosis of metastatic cancer requires increased patient support and healthcare resource utilization. The patient voice should be heard and incorporated into care planning to improve the overall experience of individual with metastatic cancer. Concept analysis. Dictionary definitions and scientific literature from electronic databases, including PubMed. Using Walker and Avants method of concept analysis, we identified attributes, antecedents, and consequences. Patient voice is defined as verbal or written communication by the patient to their healthcare partner to positively influence their quantity and quality of life. Attributes of patient voice include context, healthcare partner, safety, time, active listening, communication, and incorporation. Antecedents to patient voice include patient, baseline knowledge, continuing education, medical system culture, and emotional intelligence, and consequences include improved quality of life, adherence to treatment plan, overall satisfaction, and sense of control. Every instance of patient voice prepares the individual for future experiences that can positively impact their care. The concept of patient voice is vital to integrate into care to ensure individuals wishes and goals are incorporated in advanced disease populations. Systematically incorporating the patient voice into the care of individuals with metastatic cancer will allow patients to experience treatment and the progression to end-of-life care according to their preferences. |
36,227,121 | Distinct Uroplakin II Staining Pattern in Apocrine Breast Carcinoma. | Uroplakin II (UPII) has been shown as a highly specific marker of urothelial carcinoma however, it can also stain subtypes of apocrine-differentiated breast carcinoma. Given that urothelium and breast epithelium share other common immunohistochemical markers, such as CK7 and GATA3, this can lead to a potential diagnostic pitfall. We stained a cohort of triple-negative breast cancer with UPII. Compared with the diffuse, cytoplasmic staining in urothelial carcinoma, UPII was positive in 38.9% of apocrine carcinoma (718) with a course, granular cytoplasmic staining pattern and negative in all nonapocrine triple-negative breast cancer cases. Furthermore, the same staining pattern was present in all apocrine metaplasia of the breast (44) and apocrine sweat glands in normal skin (66). This distinct subcellular localization of UPII staining in breast carcinoma can offer a potential solution to the above diagnostic pitfall. |
36,227,008 | CXCR1 participates in bone cancer pain induced by Walker 256 breast cancer cells in female rats. | Bone cancer pain (BCP) is a clinically intractable mixed pain, involving inflammation and neuropathic pain, and its mechanisms remain unclear. CXC chemokine receptor 1 (CXCR1, IL-8RA) and 2 (CXCR2, IL-8RB) are high-affinity receptors for interleukin 8 (IL8). According to previous studies, CXCR2 plays a crucial role in BCP between astrocytes and neurons, while the role of CXCR1 remains unclear. The objective of this study was to investigate the role of CXCR1 in BCP. We found that CXCR1 expression increased in the spinal dorsal horn. Intrathecal injection of CXCR1 siRNA effectively attenuated mechanical allodynia and pain-related behaviors in rats. It was found that CXCR1 was predominantly co-localized with neurons. Intrathecal injection of CXCR1-siRNA reduced phosphorylated JAK2STAT3 protein levels and the NLRP3 inflammasome (NLRP3, caspase1, and IL-1β) levels. Furthermore, in vitro cytological experiments confirmed this conclusion. The study results suggest that the spinal chemokine receptor CXCR1 activation mediates BCP through JAK2STAT3 signaling pathway and NLRP3 inflammasome (NLRP3, caspase1, and IL-1β). |
36,226,914 | ROS-Responsive Nanocomplex of aPD-L1 and Cabazitaxel Improves Intratumor Delivery and Potentiates Radiation-Mediated Antitumor Immunity. | Despite the promising benefits of immune checkpoint inhibitors (ICIs) in clinical cancer treatments, the therapeutic efficacy is largely restricted by low antitumor immunity and limited intratumor delivery in solid tumors. Herein, we designed a reactive oxygen species (ROS)-responsive albumin nanocomplex of antiprogrammed cell death receptor ligand 1 (aPD-L1) and cabazitaxel (RAN-PC), which exhibited prominent tumor accumulation and intratumor permeation in 4T1 tumors. Compared with the negative control, the RAN-PC radiation treatment (RAN-PCX) produced a 3.61- and 5.10-fold enhancement in CD3 |
36,226,900 | Information needs and research priorities in long-term survivorship of breast cancer Patients and health professionals perspectives. | The objective of this work is to identify unmet information needs of long-term-survivors of breast cancer (BC) and future research needs from the perspectives of patients and health care professionals. Two online Delphi surveys were conducted. Participants in Survey 1 were patients. Participants in Survey 2 were health care professionals from both primary and secondary care involved in BC care. Both surveys included three successive rounds. The first round aimed to identify research and information needs the second round aimed to rank the relative importance of those needs the third round aimed to find consensus. The most important information needs were self-management recommendations of common health problems after treatment and complications of breast reconstruction after 5 years. The most important research priorities were related to interventions and tools to increase information provision by professionals about certain tests, diet, and coordinated action between primary and specialised care during follow-up, and indications and safety issues of pregnancy in survivors. Two fundamental ideas were identified (1) Patients request information about self-management common health problems after treatment and breast reconstruction complications. (2) Health care professionals emphasise the need for a standardised approach based on protocols, recommendations, and coordinated actions in the provision of information. Given the increasing number of BC survivors, it is essential to identify information and research needs to improve their care and health outcomes. |
36,226,863 | Pharmacokinetic study on the co-administration of abemaciclib and astragaloside IV in rats. | The co-administration of abemaciclib and astragaloside IV might occur in the treatment of breast cancer. This study evaluates the interaction between abemaciclib and astragaloside IV in rats and describes the potential mechanism. Male Sprague Dawley rats were randomly divided into four groups single dose of abemaciclib (control), abemaciclib 50 mgkgd astragaloside IV, abemaciclib 100 mgkgd astragaloside IV, and abemaciclib 150 mgkgd astragaloside IV. Abemaciclib and astragaloside IV were orally administrated, and astragaloside IV was pre-administrated for 7 d in the co-administrated groups. The pharmacokinetics and transport of abemaciclib were assessed in the absence or presence of astragaloside IV. In mechanism, the activity of CYP3A4 was estimated in human liver microsomes in the presence of astragaloside IV. Astragaloside IV significantly increased the C The co-administration of abemaciclib and astragaloside IV induced the increasing systemic exposure of abemaciclib through the inhibition of CYP3A4. Further clinical validations could be carried out according to the study design of the present investigation. |
36,226,804 | Diagnostic performance of tomosynthesis, digital mammography and a dedicated digital specimen radiography system versus pathological assessment of excised breast lesions. | The aim of the study was to compare the performance of full-field digital mammography (FFDM), digital breast tomosynthesis and a dedicated digital specimen radiography system (SRS) in consecutive patients, and to compare the margin status of resected lesions versus pathological assessment. Resected tissue specimens from consecutive patients who underwent intraoperative breast specimen assessment following wide local excision or oncoplastic breast conservative surgery were examined by FFDM, tomosynthesis and SRS. Two independent observers retrospectively evaluated the visibility of lesions, size, margins, spiculations, calcifications and diagnostic certainty, and chose the best performing method in a blinded manner. We evaluated 216 specimens from 204 patients. All target malignant lesions were removed with no tumouron-ink. One papilloma had positive microscopic margins and one patient underwent reoperation owing to extensive Tomosynthesis was superior to SRS and FFDM for detecting and evaluating the target lesions, spiculations and calcifications, and was therefore more reliable for assessing complete excision of breast lesions. |
36,226,608 | A monolateral pigmented lesion of the nipple. | Pigmented mammary Pagets disease is a very rare variant of mammary Pagets disease linked to an underlying carcinoma in almost all cases. We present the case of a 62-year-old female patient who came to our attention for the evaluation of a monolateral asymptomatic pigmented lesion of the right nipple, which turned out to be a pigmented mammary Pagets disease unassociated to an underlying malignancy - an extremely rare entity only anecdotally reported in literature. The two main peculiarities of our patients lesion, the importance of immunohistochemistry in the differential diagnosis and the theories on its pathogenesis are discussed. Further studies are necessary to establish the best treatment options. Click here for the corresponding questions to this CME article. |
36,226,600 | Development and validation of radiomics machine learning model based on contrast-enhanced computed tomography to predict axillary lymph node metastasis in breast cancer. | Preoperative identification of axillary lymph node metastasis can play an important role in treatment selection strategy and prognosis evaluation. This study aimed to establish a clinical nomogram based on lymph node images to predict lymph node metastasis in breast cancer patients. A total of 193 patients with non-specific invasive breast cancer were divided into training (n 135) and validation set (n 58). Radiomics features were extracted from lymph node imagesinstead of tumor region, and the least absolute shrinkage and selection operator logistic algorithm was used to select the extracted features and generate radiomics scores. Then, the important clinical factors and radiomics scores were integrated into a nomogram. A receiver operating characteristic curve was used to evaluate the nomogram, and the clinical benefit of using the nomogram was evaluated by decision curve analysis. We found that clinical N stage and radiomics scores were independent clinical predictors. Besides, the nomogram accurately predicted axillary lymph node metastasis, yielding an area under the receiver operating characteristic curve of 0.95 (95% confidence interval 0.93-0.98) in the validation set, indicating satisfactory calibration. Decision curve analysis confirmed that the nomogram had higher clinical utility than clinical N stage or radiomics scores alone. Overall, the nomogram based on radiomics features and clinical factors can help radiologists to predict axillary lymph node metastasis preoperatively and provide valuable information for individual treatment. |
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