Development and validation of a model and nomogram for breast cancer diagnosis based on quantitative analysis of serum disease-specific haptoglobin N-glycosylation.

BACKGROUND: A better diagnostic marker is in need to distinguish breast cancer from suspicious breast lesions. The abnormal glycosylation of haptoglobin has been documented to assist cancer diagnosis. This study aims to evaluate disease-specific haptoglobin (DSHp)-ß N-glycosylation as a potential biomarker for breast cancer diagnosis. METHODS: DSHp-ß chains of 497 patients with suspicious breast lesions who underwent breast surgery were separated from serum immunoinflammatory-related protein complexes. DSHp-ß N-glycosylation was quantified by mass spectrometric analysis. After missing data imputation and propensity score matching, patients were randomly assigned to the training set (n = 269) and validation set (n = 113). Logistic regression analysis was employed in model and nomogram construction. The diagnostic performance was analyzed with receiver operating characteristic and calibration curves. RESULTS: 95 N-glycopeptides at glycosylation sites N207/N211, N241, and N184 were identified in 235 patients with benign breast diseases and 262 patients with breast cancer. DSHp-ß N-tetrafucosyl and hexafucosyl were significantly increased in breast cancer compared with benign diseases (p < 0.001 and p = 0.001, respectively). The new diagnostic model and nomogram included GN2F2, G6N3F6, GN2FS at N184, G-N&G2S2, G2&G3NFS, G2N3F, GN3 at N207/N211, CEA, CA153, and could reliably distinguish breast cancer from benign diseases. For the training set, validation set, and training and validation sets, the area under the curves (AUCs) were 0.80 (95% CI: 0.75-0.86, specificity: 87%, sensitivity: 62%), 0.77 (95% CI:0.69-0.86, specificity: 75%, sensitivity: 69%), and 0.80 (95% CI:0.76-0.84, specificity: 77%, sensitivity: 68%), respectively. CEA, CA153, and their combination yielded AUCs of 0.62 (95% CI: 0.56-0.67, specificity: 29%, sensitivity: 90%), 0.65 (95% CI: 0.60-0.71, specificity: 74%, sensitivity: 51%), and 0.67 (95% CI: 0.62-0.73, specificity: 60%, sensitivity: 68%), respectively. CONCLUSIONS: The combination of DSHp-ß N-glycopeptides, CEA, and CA153 might be a better serologic marker to differentiate between breast cancer and benign breast diseases. The dysregulated N-glycosylation of serum DSHp-ß could provide insights into breast tumorigenesis.

Predicting three or more metastatic nodes using contrast-enhanced lymphatic US findings in early breast cancer.

OBJECTIVES: To develop and validate a nomogram for predicting ≥ 3 metastatic axillary lymph nodes (ALNs) in early breast cancer with no palpable axillary adenopathy by clinicopathologic data, contrast-enhanced (CE) lymphatic ultrasound (US), and grayscale findings of sentinel lymph nodes (SLNs). MATERIALS AND METHODS: Women with T1-2N0 invasive breast cancer were consecutively recruited for the CE lymphatic US. Patients from Center 1 were grouped into development and internal validation cohorts at a ratio of 2:1. The external validation cohort was constructed from Center 2. The clinicopathologic data and US findings of SLNs were analyzed. A nomogram was developed to predict women with ≥ 3 metastatic ALNs. Nomogram performance was assessed with the area under the receiver operating characteristic curve (AUC) and calibration curve analysis. RESULTS: One hundred seventy-nine from Center 1 were considered the development cohorts. The remaining 90 participants from Center 1 were internal cohorts and 197 participants from Center 2 were external validation cohorts. The US findings of no enhancement (odds ratio (OR), 15.3; p = 0.01), diffuse (OR, 19.1; p = 0.01) or focal eccentric (OR, 27.7; p = 0.003) cortical thickening, and absent hilum (OR, 169.7; p < 0.001) were independently associated with ≥ 3 metastatic ALNs. Compared to grayscale US or CE lymphatic US alone, the nomogram showed the highest AUC of 0.88 (0.85, 0.91). The nomogram showed a calibration slope of 1.0 (p = 0.80-0.81; Brier = 0.066-0.067) in validation cohorts in predicting ≥ 3 metastatic ALNs. CONCLUSION: Patients likely to have ≥ 3 metastatic ALNs were identified by combining the lymphatic and grayscale US findings of SLNs. Our nomogram could aid in multidisciplinary treatment decision-making. TRIAL REGISTRATION: This trial is registered on www.chictr.org.cn : ChiCTR2000031231. Registered March 25, 2020. CRITICAL RELEVANCE STATEMENT: A nomogram combining lymphatic CEUS and grayscale US findings of SLNs could identify early breast cancer patients with low or high axillary tumor burden preoperatively, which is more applicable to the Z0011 era. Our nomogram could be useful in aiding multidisciplinary treatment decision-making for patients with early breast cancer. KEY POINTS: • CEUS can help identify and diagnose SLN in early breast cancer preoperatively. • Combining lymphatic and grayscale US findings can predict axillary tumor burden. • The nomogram showed a high diagnostic value in validation cohorts.

Nomogram prediction of the 70-gene signature (MammaPrint) binary and quartile categorized risk using medical history, imaging features and clinicopathological data among Chinese breast cancer patients.

BACKGROUND: The 70-gene signature (70-GS, MammaPrint) test has been recommended by the main guidelines to evaluate prognosis and chemotherapy benefit of hormonal receptor positive human epidermal receptor 2 negative (HR + /Her2-) early breast cancer (BC). However, this expensive assay is not always accessible and affordable worldwide. Based on our previous study, we established nomogram models to predict the binary and quartile categorized risk of 70-GS. METHODS: We retrospectively analyzed a consecutive cohort of 150 female patients with HR + /Her2- BC and eligible 70-GS test. Comparison of 40 parameters including the patients' medical history risk factors, imaging features and clinicopathological characteristics was performed between patients with high risk (N = 62) and low risk (N = 88) of 70-GS test, whereas risk calculations from established models including Clinical Treatment Score Post-5 years (CTS5), Immunohistochemistry 3 (IHC3) and Nottingham Prognostic Index (NPI) were also compared between high vs low binary risk of 70-GS and among ultra-high (N = 12), high (N = 50), low (N = 65) and ultra-low (N = 23) quartile categorized risk of 70-GS. The data of 150 patients were randomly split by 4:1 ratio with training set of 120 patients and testing set 30 patients. Univariate analyses and multivariate logistic regression were performed to establish the two nomogram models to predict the the binary and quartile categorized risk of 70-GS. RESULTS: Compared to 70-GS low-risk patients, the high-risk patients had significantly less cardiovascular co-morbidity (p = 0.034), more grade 3 BC (p = 0.006), lower progesterone receptor (PR) positive percentage (p = 0.007), more Ki67 high BC (≥ 20%, p < 0.001) and no significant differences in all the imaging parameters of ultrasound and mammogram. The IHC3 risk and the NPI calculated score significantly correlated with both the binary and quartile categorized 70-GS risk classifications (both p < 0.001). The area under curve (AUC) of receiver-operating curve (ROC) of nomogram for binary risk prediction were 0.826 (C-index 0.903, 0.799-1.000) for training and 0.737 (C-index 0.785, 0.700-0.870) for validation dataset respectively. The AUC of ROC of nomogram for quartile risk prediction was 0.870 (C-index 0.854, 0.746-0.962) for training and 0.592 (C-index 0.769, 0.703-0.835) for testing set. The prediction accuracy of the nomogram for quartile categorized risk groups were 55.0% (likelihood ratio tests, p < 0.001) and 53.3% (p = 0.04) for training and validation, which more than double the baseline probability of 25%. CONCLUSIONS: To our knowledge, we are the first to establish easy-to-use nomograms to predict the individualized binary (high vs low) and the quartile categorized (ultra-high, high, low and ultra-low) risk classification of 70-GS test with fair performance, which might provide information for treatment choice for those who have no access to the 70-GS testing.

Case Report: A 13-year-old adolescent diagnosed as malignant phyllodes tumor combined with rhabdomyosarcoma differentiation.

Phyllodes tumor (PT) is an infrequent type of breast neoplasm, constituting a mere 0.5%-1.5% of the entirety of breast tumors. The malignant phyllodes tumor (MPT) comprises only 15% of all phyllodes tumors, and its transformation into rhabdomyosarcoma (RMS) is exceedingly rare in clinical practice. Given its insensitivity to chemotherapy and radiotherapy, treatment options for MPT patients are limited, leaving complete surgical resection as the only option. Therefore, it is imperative to investigate the effective utilization of the heterogeneous differentiation characteristics of MPT to expand treatment alternatives for these patients. In this case report, we represent a 13-year-old adolescent diagnosed with giant breast MPT with RMS differentiation and pulmonary metastasis. The initial step in the treatment process involved radical surgical resection, followed by the administration of four cycles of VDC/IC chemotherapy, which is widely recognized as the standard chemotherapy for RMS. Regrettably, the delay in initiating chemotherapy resulted in minimal observable changes in the size of the pulmonary metastatic nodule. Additionally, a comprehensive literature review on the characterization of MPT with heterogeneous differentiation was conducted to enhance comprehension of the diagnosis and treatment of this uncommon disease in clinical practice. Meanwhile, this case also reminds the doctors that when we diagnose a patient as MPT, it is crucial to consider its heterogenous nature and promptly initiate adjuvant treatment. By targeting the differentiation element of MPT, it becomes feasible to overcome the previously perceived limitation of surgical intervention as the sole treatment option.

Unveiling the regulatory mechanisms of salicylate degradation gene cluster cehGHIR4 in Rhizobium sp. strain X9.

In a previous study, the novel gene cluster cehGHI was found to be involved in salicylate degradation through the CoA-mediated pathway in Rhizobium sp. strain X9 (Mol Microbiol 116:783-793, 2021). In this study, an IclR family transcriptional regulator CehR4 was identified. In contrast to other regulators involved in salicylate degradation, cehR4 forms one operon with the gentisyl-CoA thioesterase gene cehI, while cehG and cehH (encoding salicylyl-CoA ligase and salicylyl-CoA hydroxylase, respectively) form another operon. cehGH and cehIR4 are divergently transcribed, and their promoters overlap. The results of the electrophoretic mobility shift assay and DNase I footprinting showed that CehR4 binds to the 42-bp motif between genes cehH and cehI, thus regulating transcription of cehGH and cehIR4. The repeat sequences IR1 (5'-TTTATATAAA-3') and IR2 (5'-AATATAGAAA-3') in the motif are key sites for CehR4 binding. The arrangement of cehGH and cehIR4 and the conserved binding motif of CehR4 were also found in other bacterial genera. The results disclose the regulatory mechanism of salicylate degradation through the CoA pathway and expand knowledge about the systems controlled by IclR family transcriptional regulators.IMPORTANCEThe long-term residue of aromatic compounds in the environment has brought great threat to the environment and human health. Microbial degradation plays an important role in the elimination of aromatic compounds in the environment. Salicylate is a common intermediate metabolite in the degradation of various aromatic compounds. Recently, Rhizobium sp. strain X9, capable of degrading the pesticide carbaryl, was isolated from carbaryl-contaminated soil. Salicylate is the intermediate metabolite that appeared during the degradation of carbaryl, and a novel salicylate degradation pathway and the involved gene cluster cehGHIR4 have been identified. This study identified and characterized the IclR transcription regulator CehR4 that represses transcription of cehGHIR4 gene cluster. Additionally, the genetic arrangements of cehGH and cehIR4 and the binding sites of CehR4 were also found in other bacterial genera. This study provides insights into the biodegradation of salicylate and provides an application in the bioremediation of aromatic compound-contaminated environments.

SP1-Induced Upregulation of LncRNA AFAP1-AS1 Promotes Tumor Progression in Triple-Negative Breast Cancer by Regulating mTOR Pathway.

The long non-coding RNA (lncRNA) actin fiber-associated protein-1 antisense RNA 1 (AFAP1-AS1) exerted oncogenic activity in triple-negative breast cancer (TNBC). We designed this study and conducted it to investigate the upstream regulation mechanism of AFAP1-AS1 in TNBC tumorigenesis. In this work, we proved the localization of AFAP1-AS1 in the cytoplasm. We elucidated the mechanism by which the transcription factor specificity protein 1 (SP1) modulated AFAP1-AS1 in TNBC progression, which has yet to be thoroughly studied. Dual luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay revealed a strong affinity of SP1 toward the promoter regions P3 of AFAP1-AS1, proving the gene expression regulation of AFAP1-AS1 via SP1 in TNBC. Additionally, SP1 could facilitate the tumorigenesis of TNBC cells in vitro and in vivo by regulating the AFAP1-AS1 expression. Furthermore, silenced AFAP1-AS1 suppressed the expression of genes in the mTOR pathway, such as eukaryotic translation initiation factor 4B (EIF4B), mitogen-activated protein kinase-associated protein 1 (MAPKAP1), SEH1-like nucleoporin (SEH1L), serum/glucocorticoid regulated kinase 1 (SGK1), and its target NEDD4-like E3 ubiquitin protein ligase (NEDD4L), and promoted the gene expression of s-phase kinase-associated protein 2 (SKP2). Overall, this study emphasized the oncogenic role of SP1 and AFAP1-AS1 in TNBC and illustrated the AFAP1-AS1 upstream interaction with SP1 and the downstream modulatory of mTOR signaling, thus offering insights into the tumorigenesis mechanism in TNBC.

Breast cancer pre-clinical screening using infrared thermography and artificial intelligence: a prospective, multicentre, diagnostic accuracy cohort study.

BACKGROUND: Given the limited access to breast cancer (BC) screening, the authors developed and validated a mobile phone-artificial intelligence-based infrared thermography (AI-IRT) system for BC screening. MATERIALS AND METHODS: This large prospective clinical trial assessed the diagnostic performance of the AI-IRT system. The authors constructed two datasets and two models, performed internal and external validation, and compared the diagnostic accuracy of the AI models and clinicians. Dataset A included 2100 patients recruited from 19 medical centres in nine regions of China. Dataset B was used for independent external validation and included 102 patients recruited from Langfang People's Hospital. RESULTS: The area under the receiver operating characteristic curve of the binary model for identifying low-risk and intermediate/high-risk patients was 0.9487 (95% CI: 0.9231-0.9744) internally and 0.9120 (95% CI: 0.8460-0.9790) externally. The accuracy of the binary model was higher than that of human readers (0.8627 vs. 0.8088, respectively). In addition, the binary model was better than the multinomial model and used different diagnostic thresholds based on BC risk to achieve specific goals. CONCLUSIONS: The accuracy of AI-IRT was high across populations with different demographic characteristics and less reliant on manual interpretations, demonstrating that this model can improve pre-clinical screening and increase screening rates.

The Prognostic Value of the Age-Adjusted Charlson Comorbidity Index Among the Elderly with Breast Cancer.

Purpose: This study aimed to assess the effect of comorbidities on prognosis using the Age-adjusted Charlson Comorbidity Index (ACCI) among the elderly with breast cancer (BC). Methods: This study included 745 patients divided into two groups following the ACCI score (≤3 vs >3). Multivariate logistic regression analysis was conducted for all kinds of outcomes, including BC-specific death (BCSD) and non-breast cancer-specific death (NBCSD). The Kaplan-Meier curves were plotted, and survival analysis was conducted for disease-free survival (DFS), overall survival (OS), BC-specific survival (BCSS), and non-BCSS (NBCSS). Results: A significantly higher NBCSD was found in the high-score (ACCI > 3) group than in the low-score (ACCI < 3) group (p = 0.032). The multivariate logistic regression analysis revealed ACCI score as an independent affecting factor for all-cause death (hazard ratio [HR] = 0.42, 95% confidence interval [CI]: 0.22-0.83, p = 0.012) and NBCSD (HR = 0.41, 95% CI: 0.20-0.87, p = 0.020). The Kaplan-Meier curves revealed statistical differences only in NBCSS between the two groups (p = 0.039). Subgroup analysis revealed a worse prognosis in the high-score group for OS and NBCSS among hormone receptor-positive participants and those who without undergoing axillary dissection or receiving chemotherapy (all p < 0.05). Multivariate Cox regression analysis revealed ACCI as an independent prognostic predictor for OS (HR = 2.18, 95% CI: 1.22-3.92, p = 0.009) and NBCSS (HR = 2.04, 95% CI: 1.02-4.08, p = 0.044). Conclusion: ACCI was indeed an effective indicator of the effects of comorbidities on survival among elderly patients with BC. However, the co-effect from age and comorbidities was not significant enough on cancer-specific prognosis, although it exerted a significant effect on treatments received.

A nomogram for individually predicting overall survival for elderly patients with early breast cancer: a consecutive cohort study.

Background: Elderly patients with breast cancer are highly heterogeneous, and tumor load and comorbidities affect patient prognosis. Prediction models can help clinicians to implement tailored treatment plans for elderly patients with breast cancer. This study aimed to establish a prediction model for breast cancer, including comorbidities and tumor characteristics, in elderly patients with breast cancer. Methods: All patients were ≥65 years old and admitted to the Peking Union Medical College Hospital. The clinical and pathological characteristics, recurrence, and death were observed. Overall survival (OS) was analyzed using the Kaplan-Meier curve and a prediction model was constructed using Cox proportional hazards model regression. The discriminative ability and calibration of the nomograms for predicting OS were tested using concordance (C)-statistics and calibration plots. Clinical utility was demonstrated using decision curve analysis (DCA). Results: Based on 2,231 patients, the 5- and 10-year OS was 91.3% and 78.4%, respectively. We constructed an OS prediction nomogram for elderly patients with early breast cancer (PEEBC). The C-index for OS in PEEBC in the training and validation cohorts was 0.798 and 0.793, respectively. Calibration of the nomogram revealed a good predictive capability, as indicated by the calibration plot. DCA demonstrated that our model is clinically useful. Conclusion: The nomogram accurately predicted the 3-year, 5-year, and 10-year OS in elderly patients with early breast cancer.

Dermis-retained breast dermo-glandular flap: a new surgical approach for granulomatous lobular mastitis.

Background: Granulomatous lobular mastitis (GLM) is characterized by nonspecific chronic inflammation concentrated in breast lobules. Surgical resection is one of the most common treatment options for GLM. On the basis of our previous use of Breast Dermo-Glandular Flap (BDGF), we designed a new surgical approach for GLM, especially for cases where the focus is close to the nipple. Here we describe this new treatment approach. Methods: In Peking Union Medical College Hospital (PUMCH) and Beijing Dangdai Hospital during January 2020-June 2021, we enrolled all 18 GLM patients who underwent surgery with the use of Dermis-Retained BDGF. All patients were women; most of the patients were 18-50 years old (88%); and the most common clinical manifestation of GLM was breast mass (60%). Then, we collected and analyzed data about the surgery and outcomes (drainage tubes moving time, relapse, patients' shape satisfaction). We regarded GLM recurrence on the same side as relapse. If there was no complication and the patient's satisfaction was excellent or good, we rated the surgery as successful. We recorded the occurrence of all common postsurgical complications of the breast. Results: The debridement area was 3-5.5 (4.3 ± 0.7) cm; surgery time was 78-119 (95.6 ± 11.6) min; and mean debridement time (27.8 ± 8.9 min) was shorter than the time to obtain and transplant the flap (47.5 ± 12.9 min). Blood loss was less than 139 ml. As for bacterial culture, two patients had positive results, but they had no symptoms. No surgery-related complications happened. In terms of the outcomes, all of the drainage tubes were removed in less than 5 days, and only one patient experienced relapse after 1 year of surgery during the follow-up. The patients' satisfaction with the breast shape was as follows: excellent (50%), good (22%), acceptable (22%), and poor (6%). Conclusion: For GLM patients refractory to conservative therapy or former unsatisfactory surgical management whose lesion is in the vicinity of the nipple and larger than 3 cm, Dermis-Retained BDGF is a suitable approach to fill the after-debridement defect below the nipple-areola and achieve a relatively satisfactory cosmetic outcome.

Big data analysis of water quality monitoring results from the Xiang River and an impact analysis of pollution management policies.

Water pollution prevention and control of the Xiang River has become an issue of great concern to China's central and local governments. To further analyze the effects of central and local governmental policies on water pollution prevention and control for the Xiang River, this study performs a big data analysis of 16 water quality parameters from 42 sections of the mainstream and major tributaries of the Xiang River, Hunan Province, China from 2005 to 2016. This study uses an evidential reasoning-based integrated assessment of water quality and principal component analysis, identifying the spatiotemporal changes in the primary pollutants of the Xiang River and exploring the correlations between potentially relevant factors. The analysis showed that a series of environmental protection policies implemented by Hunan Province since 2008 have had a significant and targeted impact on annual water quality pollutants in the mainstream and tributaries. In addition, regional industrial structures and management policies also have had a significant impact on regional water quality. The results showed that, when examining the changes in water quality and the effects of pollution control policies, a big data analysis of water quality monitoring results can accurately reveal the detailed relationships between management policies and water quality changes in the Xiang River. Compared with policy impact evaluation methods primarily based on econometric models, such a big data analysis has its own advantages and disadvantages, effectively complementing the traditional methods of policy impact evaluations. Policy impact evaluations based on big data analysis can further improve the level of refined management by governments and provide a more specific and targeted reference for improving water pollution management policies for the Xiang River.

A case report of primary angiosarcoma of the breast.

Background: Breast Angiosarcoma can be divided into primary breast angiosarcoma (PBA) and second breast angiosarcoma (SBA). PBA is rare malignant breast cancer with poor outcomes. PBA usually occurs in women between 30-40 years old. PBA does not have a specific clinical manifestation. Clinically, PBA presents with a rapidly enlarging breast mass and skin involvement with skin color changes. Ultrasonography of PBA can be hypoechoic or hyperechoic, or mixed disordered areas. Microscopically, PBA can be classified into three grades according to the degree of differentiation, and the grade is related to the prognosis. And PBA can also express vascular endothelial markers. The main treatment for PBA is surgery, especially mastectomy. There are other treatments, such as chemotherapy and radiotherapy, but their effectiveness needs further confirmation. Targeted drugs may be helpful. Case Description: A 32-year-old woman with main clinical presentation of a rapidly growing mass located in the upper inner quadrant of the right breast with skin involvement. PBA was diagnosed with first extended local resection, and then the patient underwent a second right mastectomy. The patient is now undergoing chemotherapy. Conclusions: Since this is a rare form of breast cancer, we report this case to raise the attention of breast surgeons to avoid misdiagnoses.

Identification of genetic and immune signatures for the recurrence of HER2-positive breast cancer after trastuzumab-based treatment.

PURPOSE: To determine the genetic and immune features associated with the recurrence of human epidermal growth factor receptor2-positive (HER2 +) breast cancer (BC) after trastuzumab-based treatment. METHODS: A retrospective cohort study of 48 patients who received trastuzumab-based treatment was divided into recurrent and non-recurrent groups according to clinical follow-up. Baseline samples from all 48 patients were analyzed for genetic variation, HLA allele type, gene expression, and immune features, which were linked to HER2 + BC recurrence. Statistics included logistic regression models, Kaplan-Meier plots, and Univariate Cox proportional hazards models. RESULTS: Compared with the non-recurrent group, the extracellular matrix-related pathway and 3 Hallmark gene sets were enriched in the recurrent group. The infiltration levels of immature B cells and activated B cells were significantly increased in the non-recurrent group, which correlated remarkably with improved overall survival (OS) in two other published gene expression datasets, including TCGA and METABRIC. In the TCGA cohort (n = 275), activated B cells (HR 0.23, 95%CI 0.13-0.43, p < 0.0001), and immature B cells (HR 0.26, 95%CI 0.12-0.59, p < 0.0001). In the METABRIC cohort (n = 236), activated B cells (HR 0.60, 95%CI 0.43-0.83, p = 0.002), and immature B cells (HR 0.65, 95%CI 0.47-0.91, p = 0.011). Cox regression suggested that immature B cells and activated B cells were protective factors for outcome OS. CONCLUSIONS: Aberrant activation of multiple pathways and low baseline tumor-infiltrating B cells are related to HER2 + BC trastuzumab-based recurrence, which primarily affects the antitumor activity of trastuzumab.

Syndecan-1 as an immunogene in Triple-negative breast cancer: regulation tumor-infiltrating lymphocyte in the tumor microenviroment and EMT by TGFb1/Smad pathway.

BACKGROUND: Immune checkpoint inhibitors are the most studied forms of immunotherapy for triple-negative breast cancer (TNBC). The Cancer Genome Map (TCGA) and METABRIC project provide large-scale cancer samples that can be used for comprehensive and reliable immunity-related gene research. METHODS: We analyzed data from TCGA and METABRIC and established an immunity-related gene prognosis model for breast cancer. The SDC1 expression in tumor and cancer associated fibroblasts (CAFs) was then observed in 282 TNBC patients by immunohistochemistry. The effects of SDC1 on MDA-MB-231 proliferation, migration and invasion were evaluated. Qualitative real-time PCR and western blotting were performed to identify mRNA and protein expression, respectively. RESULTS: SDC1, as a key immunity-related gene, was significantly correlated with survival in the TCGA and METABRIC databases, while SDC1 was found to be highly expressed in TNBC in the METABRIC database. In the TNBC cohort, patients with high SDC1 expression in tumor cells and low expression in CAFs had significantly lower disease-free survival (DFS) and fewer tumor-infiltrating lymphocytes (TILs). The downregulation of SDC1 decreased the proliferation of MDA-MB-231, while promoting the migration of MDA-MB-231 cells by reducing the gene expression of E-cadherin and TGFb1 and activating p-Smad2 and p-Smad3 expression. CONCLUSION: SDC1 is a key immunity-related gene that is highly expressed TNBC patients. Patients with high SDC1 expression in tumors and low expression in CAFs had poor prognoses and low TILs. Our findings also suggest that SDC1 regulates the migration of MDA-MB-231 breast cancer cells through a TGFb1-Smad and E-cadherin-dependent mechanism.

Breast-conserving surgery without axillary surgery and radiation versus mastectomy plus axillary dissection in elderly breast cancer patients: A retrospective study.

Background: The high relative mortality rate in elderly breast cancer patients is most likely the result of comorbidities rather than the tumor load. Foregoing axillary lymph node dissection or omitting radiotherapy after breast-conserving surgery (BCS) does not affect the prognosis of elderly breast cancer patients. We sought to assess the safety of breast-conserving surgery without axillary lymph node dissection as well as breast and axillary radiotherapy (BCSNR) in elderly patients with early-stage breast cancer. Methods: We retrospectively included 541 consecutive breast cancer patients aged over 70 years with clinically negative axillary lymph nodes in one clinical center. Of these patients, 181 underwent mastectomy plus axillary lymph node dissection (MALND) with negative axillary cleaning and 360 underwent BCSNR. Results: After a median follow-up of 5 years, there was no significant difference between the BCSNR and MALND groups in either distant recurrence-free survival (DRFS) (p=0.990) or breast cancer-specific survival (p=0.076). Ipsilateral axillary disease was found in 11 (3.1%) patients in the BCSNR group and 3 (1.7%) patients in the MALND group; this difference was not significant (p=0.334). We did not observe a significant difference in distant recurrence between the groups (p=0.574), with 25 (6.9%) patients in the BCSNR group experiencing distant recurrence compared to 15 (8.3%) patients in the MALND group. Our findings did show a significant difference in ipsilateral breast cancer recurrence (IBTR), with 31 (8.6%) patients in the BCSNR group experiencing IBTR compared to only 2 (1.1%) patients in the MALND group (p=0.003). Conclusion: BCSNR is a safe treatment option for elderly breast cancer patients with clinically negative axillary lymph nodes.

Increased 18 F-Fluoroestradiol Uptake of Radiation Pneumonitis in a Patient With Metastatic Breast Cancer.

ABSTRACT: A 42-year-old woman diagnosed with de-novo stage IV breast cancer underwent 18 F-fluoroestradiol (FES) PET/CT to evaluate the estrogen receptor status of metastatic lesions. The largest pulmonary nodule showed obvious FES uptake, consistent with pulmonary metastases from breast cancer. Interestingly, the images revealed a striking accumulation of FES in ground-glass attenuation in the left lobe of lung, suggestive of radiation pneumonitis.

Network evolution of regional brain volumes in young children reflects neurocognitive scores and mother's education.

The maturation of regional brain volumes from birth to preadolescence is a critical developmental process that underlies emerging brain structural connectivity and function. Regulated by genes and environment, the coordinated growth of different brain regions plays an important role in cognitive development. Current knowledge about structural network evolution is limited, partly due to the sparse and irregular nature of most longitudinal neuroimaging data. In particular, it is unknown how factors such as mother's education or sex of the child impact the structural network evolution. To address this issue, we propose a method to construct evolving structural networks and study how the evolving connections among brain regions as reflected at the network level are related to maternal education and biological sex of the child and also how they are associated with cognitive development. Our methodology is based on applying local Fréchet regression to longitudinal neuroimaging data acquired from the RESONANCE cohort, a cohort of healthy children (245 females and 309 males) ranging in age from 9 weeks to 10 years. Our findings reveal that sustained highly coordinated volume growth across brain regions is associated with lower maternal education and lower cognitive development. This suggests that higher neurocognitive performance levels in children are associated with increased variability of regional growth patterns as children age.

Molecular imaging of HER2 expression in breast cancer patients using a novel peptide-based tracer 99mTc-HP-Ark2: a pilot study.

BACKGROUND: Due to the temporal and spatial heterogeneity of human epidermal growth factor receptor 2 (HER2) expression in breast tumors, immunohistochemistry (IHC) cannot accurately reflect the HER2 status in real time, which may cause misguided treatment decisions. HER2-specific imaging can noninvasively determine HER2 status in primary and metastatic tumors. In this study, HER2 expression in breast cancer patients was determined in vivo by SPECT/CT of 99mTc-HP-Ark2, comparing with PET/CT of 18F-FDG lesion by lesion. METHODS: A novel HER2-targeted peptide probe 99mTc-HP-Ark2 was constructed. Biodistribution and nanoScan SPECT/CT imaging were performed in mice models. The correlation between the quantified tumor uptake and HER2 expression in tumor cells was analyzed. In the pilot clinical study, a total of 34 breast cancer patients (mean age ± SD: 49 ± 10 y) suspected of having breast cancer according to mammography or ultrasonography were recruited at Peking Union Medical College Hospital, and 99mTc-HP-Ark2 SPECT/CT and 18F-FDG PET/CT were carried out with IHC and fluorescence in situ hybridization as validation. RESULTS: Small animal SPECT/CT of 99mTc-HP-Ark2 clearly identified tumors with different HER2 expression. The quantified tumor uptake and tumor HER2 expression showed a significant linear correlation (r = 0.932, P < 0.01). Among the 36 primary lesions in the 34 patients, when IHC (2 +) or IHC (3 +) was used as the positive evaluation criterion, 99mTc-HP-Ark2 SPECT/CT imaging with a tumor-to-background ratio of 1.44 as the cutoff value reflected the HER2 status with sensitivity of 89.5% (17/19), specificity of 88.2% (15/17) and accuracy of 88.9% (32/36), while the 18F-FDG PET/CT showed sensitivity of 78.9% (15/19), specificity of 70.6% (12/17) and accuracy of 75.0% (27/36). In particular, 100% of IHC (3 +) tumors were all identified by 99mTc-HP-Ark2 SPECT/CT imaging. CONCLUSION: 99mTc-HP-Ark2 SPECT/CT can provide a specific, noninvasive evaluation of HER2 expression in breast cancer, showing great potential to guide HER2-targeted therapies in clinical practice. CLINICALTRIALS: gov Trial registration: NCT04267900. Registered 11th February 2020. Retrospectively registered, https://www. CLINICALTRIALS: gov/ct2/results?pg=1&load=cart&id=NCT04267900 .

A novel nomogram for the preoperative prediction of sentinel lymph node metastasis in breast cancer.

BACKGROUND OR PURPOSE: A practical noninvasive method to identify sentinel lymph node (SLN) status in breast cancer patients, who had a suspicious axillary lymph node (ALN) at ultrasound (US), but a negative clinical physical examination is needed. To predict SLN metastasis using a nomogram based on US and biopsy-based pathological features, this retrospective study investigated associations between clinicopathological features and SLN status. METHODS: Patients treated with SLN dissection at four centers were apportioned to training, internal, or external validation sets (n = 472, 175, and 81). Lymph node ultrasound and pathological characteristics were compared using chi-squared and t-tests. A nomogram predicting SLN metastasis was constructed using multivariate logistic regression models. RESULTS: In the training set, statistically significant factors associated with SLN+ were as follows: histology type (p < 0.001); progesterone receptor (PR: p = 0.003); Her-2 status (p = 0.049); and ALN-US shape (p = 0.034), corticomedullary demarcation (CMD: p < 0.001), and blood flow (p = 0.001). With multivariate analysis, five independent variables (histological type, PR status, ALN-US shape, CMD, and blood flow) were integrated into the nomogram (C-statistic 0.714 [95% CI: 0.688-0.740]) and validated internally (0.816 [95% CI: 0.784-0.849]) and externally (0.942 [95% CI: 0.918-0.966]), with good predictive accuracy and clinical applicability. CONCLUSION: This nomogram could be a direct and reliable tool for individual preoperative evaluation of SLN status, and therefore aids decisions concerning ALN dissection and adjuvant treatment.