Comparison of the Response to Neoadjuvant Therapy Between Immunohistochemistry HER2 (3+) and HER2 (2+)/ISH+ Early-Stage Breast Cancer: A Retrospective Multicenter Cohort Study.

BACKGROUND: According to the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria, both immunohistochemical HER2 (3+) and HER2 (2+)/in situ hybridization (ISH) amplified [HER2 (2+)/ISH+] breast cancers (BCs) fall under the HER2-positive BC category. However, there is a lack of studies exploring the difference of neoadjuvant therapeutic response between patients with HER2 (3+) and HER2 (2+)/ISH+ early BC. We aimed to evaluate the neoadjuvant therapeutic response, long-term outcome, and intrinsic subtype heterogeneity between HER2 (3+) and HER2 (2+)/ISH+ BC. METHODS: We examined 2 distinct cohorts. Cohort 1 (C1) encompassed 2648 patients with HER2-positive early BC diagnoses, and they received neoadjuvant therapy (NT) and surgery between January 1, 2009 and December 31, 2022, from the Shanghai Jiao Tong University Breast Cancer Data Base. Cohort 2 (C2) comprised 135 patients with early-stage HER2-positive BC who underwent NT and surgery at Henan Cancer Hospital from January 1, 2021, to December 31, 2022. These patients had available genomic and transcriptomic data at their disposal. C1 and C2 were further categorized into 2 patient cohorts as follows: (1) patients with IHC HER2 (3+) early BC [HER2 (3+) group], (2) patients with HER2 (2+)/ISH+ early BC [HER2 (2+)/ISH+ group]. Among those excluded from the analysis were patients < 18 years or >80 years of age. Clinicopathological parameters, long-term outcomes, and intrinsic subtypes were analyzed. RESULTS: In the C1 population, 83.7% had HER2 (3+) BC, while 16.3% had HER2 (2+)/ISH+ BC. Patients with HER2 (3+) had a significantly higher pathological complete response (PCR) rate (38.9%) than patients with HER2 (2+)/ISH+ (18.1%; P < .001), but the disease-free survival (DFS) was comparable after a median follow-up of 29 months (P = .556). The addition of trastuzumab or trastuzumab plus pertuzumab to neoadjuvant chemotherapy (NAC) improved PCR rates and DFS in HER2 (3+) BC but not in HER2 (2+)/ISH+ BC. In the C2 population, 97.75% HER2 (3+) and 52.17% HER2 (2+)/ISH+ were HER2 enriched (HER2E) subtype (P < .001). HER2E showed increased PCR rates compared to non-HER2E (P = .004). CONCLUSIONS: Compared to HER2 (3+) BC, the limited effectiveness of neoadjuvant trastuzumab and pertuzumab therapy for HER2 (2+)/ISH+ BC is due to subtype heterogeneity. Reassessment of targeted therapy efficacy in patients with HER2 (2+)/ISH+ BC is essential.

Pinpointing Moisture: The Capacitive Detection for Standing Tree Health.

BACKGROUND: the feasibility of the capacitance method for detecting the water content in standing tree trunks was investigated using capacitance-based equipment that was designed for measuring the water content of standing tree trunks. METHODS: In laboratory experiments, the best insertion depth of the probe for standing wood was determined by measurement experiments conducted at various depths. The bark was to be peeled when specimens and standing wood were being measured. The actual water content of the test object was obtained by specimens being weighed and the standing wood being weighed after the wood core was extracted. RESULTS: A forecast of the moisture content of standing wood within a range of 0 to 180% was achieved by the measuring instrument. The feasibility of the device for basswood and fir trees is preliminarily studied. When compared to the drying method, the average error of the test results was found to be less than 8%, with basswood at 7.75%, and fir at 7.35%. CONCLUSIONS: It was concluded that the measuring instrument has a wide measuring range and is suitable for measuring wood with low moisture content, as well as standing timber with high moisture content. The measuring instrument, being small in size, easy to carry, and capable of switching modes, is considered to have a good application prospect in the field of forest precision monitoring and quality improvement.

HN1L promotes migration and invasion of breast cancer by up-regulating the expression of HMGB1.

Recent reports showed that haematological and neurological expressed 1-like (HN1L) gene participated in tumorigenesis and tumour invasion. However, the expression and role of HN1L in breast cancer remain to be investigated. Here, bioinformatics, western blot and immunohistochemistry were used to detect the expression of HN1L in breast cancer. Wound healing, transwell assay, immunofluorescence assay and mass spectrum were used to explore the role and mechanism of HN1L on the migration and invasion of breast cancer, which was confirmed in vivo using a nude mice model. Results showed that HN1L was significantly over-expressed in breast cancer tissues, which was positively correlated with M metastasis of breast cancer patients. Silencing HN1L significantly inhibited the invasion and metastasis of breast cancer cells in vitro and lung metastasis in nude mice metastasis model of breast cancer. Mechanistically, HN1L interacted with HSPA9 and affected the expression of HMGB1, playing a key role in promoting the invasion and metastasis of breast cancer cell. These results suggested that HN1L was an appealing drug target for breast cancer.

Comparison of survival in non-metastatic inflammatory and other T4 breast cancers: a SEER population-based analysis.

BACKGROUND: Previous studies have reported poor survival rates in inflammatory breast cancer (IBC) patients than non-inflammatory local advanced breast cancer (non-IBC) patients. However, until now, the survival rate of IBC and other T4 non-IBC (T4-non-IBC) patients remains unexplored. METHODS: Surveillance, Epidemiology, and End Results (SEER) database was searched to identify cases with confirmed non-metastatic IBC and T4-non-IBC who had received surgery, chemotherapy, and radiotherapy between 2010 and 2015. IBC was defined as per the American Joint Committee on Cancer (AJCC) 7th edition. Breast Cancer-Specific Survival (BCSS) was estimated by plotting the Kaplan-Meier curve and compared across groups by using the log-rank test. Cox model was constructed to determine the association between IBC and BCSS after adjusting for age, race, stage of disease, tumor grade and surgery type. RESULTS: Out of a total of 1986 patients, 37.1% had IBC and mean age was 56.6 ± 12.4. After a median follow-up time of 28 months, 3-year BCSS rate for IBC and T4-non-IBC patients was 81.4 and 81.9%, respectively (log-rank p = 0.398). The 3-year BCSS rate in HR-/HER2+ cohort was higher for IBC patients than T4-non-IBC patients (89.5% vs. 80.8%; log-rank p = 0.028), and in HR-/HER2- cohort it was significantly lower for IBC patients than T4-non-IBC patients (57.4% vs. 67.5%; log-rank p = 0.010). However, it was identical between IBC and T4-non-IBC patients in both HR+/HER2- (85.0% vs. 85.3%; log-rank p = 0.567) and HR+/HER2+ (93.6% vs. 91.0%, log-rank p = 0.510) cohorts. After adjusting for potential confounding variables, we observed that IBC is a significant independent predictor for survival of HR-/HER2+ cohort (hazards ratio [HR] = 0.442; 95% CI: 0.216-0.902; P = 0.025) and HR-/HER2- cohort (HR = 1.738; 95% CI: 1.192-2.534; P = 0.004). CONCLUSIONS: Patients with IBC and T4-non-IBC had a similar BCSS in the era of modern systemic treatment. In IBC patients, the HR-/HER2+ subtype is associated with a better outcome, and HR-/HER2- subtype is associated with poorer outcomes as compared to the T4-non-IBC patients.

Metagenomic characterization of lysine acetyltransferases in human cancer and their association with clinicopathologic features.

Lysine acetyltransferases (KATs) are a highly diverse group of epigenetic enzymes that play important roles in various cellular processes including transcription, signal transduction, and cellular metabolism. However, our knowledge of the genomic and transcriptomic alterations of KAT genes and their clinical significance in human cancer remains incomplete. We undertook a metagenomic analysis of 37 KATs in more than 10 000 cancer samples across 33 tumor types, focusing on breast cancer. We identified associations among recurrent genetic alteration, gene expression, clinicopathologic features, and patient survival. Loss-of-function analysis was carried out to examine which KAT has important roles in growth and viability of breast cancer cells. We identified that a subset of KAT genes, including NAA10, KAT6A, and CREBBP, have high frequencies of genomic amplification or mutation in a spectrum of human cancers. Importantly, we found that 3 KATs, NAA10, ACAT2, and BRD4, were highly expressed in the aggressive basal-like subtype, and their expression was significantly associated with disease-free survival. Furthermore, we showed that depletion of NAA10 inhibits basal-like breast cancer growth in vitro. Our findings provide a strong foundation for further mechanistic research and for developing therapies that target NAA10 or other KATs in human cancer.

Relationship Between ADAMTS8, ADAMTS18, and ADAMTS20 (A Disintegrin and Metalloproteinase with Thrombospondin Motifs) Expressions and Tumor Molecular Classification, Clinical Pathological Parameters, and Prognosis in Breast Invasive Ductal Carcinoma.

BACKGROUND The aim of this study was to investigate the correlations between ADAMTSs expression and breast invasive ductal carcinoma (IDC), and to offer a theoretical basis for novel treatment methods for IDC patients. MATERIAL AND METHODS Non-proliferative catheter of breast fibroadenoma (FA) and IDC were used as the normal control and experimental group, respectively. Immunohistochemical (IHC) staining and Western blot (WB) analysis was used to assess protein expression levels of ADAMTS8, ADAMTS18, and ADAMTS20 in both FA and IDC tissues. The results of IHC, the relationship between the protein expression and the tumor molecular classification, and clinical pathological parameters were all evaluated. RESULTS IHC and WB results showed that the expression of ADAMTS8/18 in IDC samples was higher than in FA samples, while the expression of ADAMTS20 in IDC samples was lower than that in FA samples. According to the results of WB, the level of ADAMTS8 was higher in the HER2+ group than in the HER2- group and FA group. The expression of ADAMTS18 in the HR+ (including ER+ and PR+) group was significantly higher than in the HR- group and FA group. The expression of ADAMTS18 protein was also higher in the Ki67+ group than in the Ki67- group. ADAMTS20 was higher in HER2+ IDC compared with the basal subtype of IDC. CONCLUSIONS ADAMTS8/18/20 levels were not significantly correlated to the molecular subtype of IDC. ADAMTS18/20 was significantly associated with histological grade of IDC. ADAMTS8 may predict poor prognosis results of IDC patients.

[Expression of HIF-1α and correlation with angiogenesis in tissue of breast cancer complicated with diabetes].

OBJECTIVE: To explore the expression of hypoxia-inducible factor 1 alpha (HIF-1α) in tissue of breast cancer complicated with diabetes and examine the correlation with vascular endothelial growth factor (VEGF) and microvascular density (MVD). METHODS: The clinical data were collected by reviewing the relevant medical records. The difference of clinicopathologic features between breast cancer patients with diabetes (diabetic group) and that of those without diabetes (control group) was analyzed retrospectively. Immunohistochemical Streptavidin-Perosidase (SP) method was used to detect the expressions of HIF-1α and VEGF in breast cancer tissue of two groups.Vascular endothelial cells were tagged with CD31 to calculate MVD. RESULTS: The patients of tumor diameter > 2 cm were 68.4% (67/98) and lymphatic metastasis rate was 59.2% (58/98) in diabetes group. And those in control group were 54.2% (58/107) and lymphatic metastasis rate was 43.9% (47/107). The inter-group difference was significant (P < 0.05).HIP-1α was expressed in both groups. The positive rate of HIF-1α was 80.6% (79/98) in diabetes group versus 64.5% (69/107) in control group (P = 0.010). The positive rate of VEGF was 86.7% (85/98) in diabetes group versus 68.2% (73/107) in control group (P = 0.002). MVD value was 113.7 ± 32.0 in diabetes group versus 104.7 ± 29.4 in control group (P = 0.003). The positive rate of VEGF in HIF-1α positive patients of diabetes group was significantly higher than that in negative counterparts (91.1% vs 68.4%, P = 0.009). The values of MVD were 117.1 ± 30.3 and 99.5 ± 35.1 respectively in both groups. And the MVD value of HIF-1α positive group was significantly higher than that of negative group (P = 0.03). CONCLUSION: Diabetic complications may play critical roles in the development and metastasis of breast cancer through enhanced angiogenesis of tumor tissue.

Identification potential biomarkers for diagnosis, and progress of breast cancer by using high-pressure photon ionization time-of-flight mass spectrometry.

BACKGROUND: In this study, exhaled breath testing has been considered a promising method for the detection and monitoring of breast cancer (BC). METHODS: A high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS) platform was used to detect volatile organic compounds (VOCs) in breath samples. Then, machine learning (ML) models were constructed on VOCs for the diagnosis of BC and its progression monitoring. Ultimately, 1981 women with useable breath samples were included in the study, of whom 937 (47.3 %) had been diagnosed with BC. VOC panels were used for ML model construction for BC detection and progression monitoring. RESULTS: On the blinded testing cohort, this VOC-based model successfully differentiated patients with and without BC with sensitivity, specificity, and area under receiver operator characteristic curve (AUC) values of 85.9 %, 90.4 %, and 0.946. The corresponding AUC values when differentiating between patients with and without lymph node metastasis (LNM) or between patients with tumor-node-metastasis (TNM) stage 0/I/II or III/IV disease were 0.840 and 0.708, respectively. While developed VOC-based models exhibited poor performance when attempting to differentiate between patients based on pathological patterns (Ductal carcinoma in situ (DCIS) vs Invasive BC (IBC)) or molecular subtypes (Luminal vs Human epidermal growth factor receptor 2 (HER2+) vs Triple-negative BC (TNBC)) of BC. CONCLUSION: Collectively, the HPPI-TOFMS-based breathomics approaches may offer value for the detection and progression monitoring of BC. Additional research is necessary to explore the fundamental mechanisms of the identified VOCs.

Axillary lymph node dissection in triple-negative or HER2-positive breast cancer patients with clinical N2 achieving pathological complete response after neoadjuvant therapy: Is it necessary?

AIM: This study aims to identify suitable candidates for axillary sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) among clinical N2 (cN2) triple-negative (TN) or HER2 positive (HER2+）breast cancer patients following neoadjuvant therapy（NAT）. BACKGROUND: Despite the substantial axillary burden in cN2 breast cancer patients, high pathological response rates can be achieved with NAT in TN or HER2+ subtypes, thus enabling potential downstaging of axillary surgery. METHODS: A retrospective analysis was conducted on data from the CSBrS-012 study, screening 709 patients with initial cN2, either HER2+ or TN subtype, from January 1, 2010 to December 31, 2020. The correlation between axillary pathologic complete response (pCR) (yPN0) and breast pCR was examined. RESULTS: Among the 177 cN2 patients who achieved breast pCR through NAT, 138 (78.0 %) also achieved axillary pCR. However, in the 532 initial clinical N2 patients who did not achieve breast pCR, residual axillary lymph node metastasis persisted in 77.4 % (412/532) of cases. The relative risk of residual axillary lymph node metastasis in patients who did not achieve breast pCR was 12.4 (8.1-19.1), compared to those who did achieve breast pCR, P < 0.001. CONCLUSION: For cN2 TN or HER2+ breast cancer patients who achieve breast pCR following NAT, consideration could be given to downstaging and performing an axillary SLNB or TAD.

[Effects of high glucose on in vitro invasiveness of human breast cancer cell line MDA-MB-435].

OBJECTIVE: To explore the effects and underlying mechanisms of high glucose on in vitro invasiveness of human breast cancer cell line MDA-MB-435. METHODS: The invasiveness of MDA-MB-435 was determined by Matrigel-coated transwell chambers. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were employed to analyze the cellular expression of matrix metalloproteinase-9/matrix metalloproteinase-2/E-cadherin (MMP-9/MMP-2/E-cadherin) gene/protein. RESULTS: The invasive breast cancer cell numbers of each group (Glu 5.5, 11 and 25 mmol/L) were 50 ± 5, 65 ± 6 and 77 ± 3 respectively. Cellular invasion was dramatically enhanced in the Glu 11 and 25 mmol/L group compared with the 5.5 mmol/L group. The MMP-9/MMP-2 protein expression increased significantly in the Glu 11 and 25 mmol/L groups compared with 5.5 mmol/L group while high glucose (Glu 11 and 25 mmol/L group) down-regulated significantly the E-cadherin mRNA/protein expression. CONCLUSION: High glucose can promote the in vitro invasiveness of human breast cancer cells through the altered expression of MMP-9/MMP-2/E-cadherin.

Exploration of the breast ductal carcinoma in situ signature and its prognostic implications.

Following the implementation of breast screening programs, the occurrence of ductal carcinoma in situ (DCIS) as an early type of neoplasia has increased. Although the prognosis is promising, 20%-50% of DCIS patients will progress to invasive ductal carcinoma (IDC) if not treated. It is essential to look for promising biomarkers for predicting DCIS prognosis. The Gene Expression Omnibus (GEO) database was used to explore the expression of genes that differed between DCIS and normal tissue in this investigation. Enrichment analysis was performed to characterize the biological role and intrinsic process pathway. The Cancer Genome Atlas Breast Cancer Dataset was used to categorize the hub genes, and the results were confirmed using the Cytoscape plugin CytoHubba and MCODE. The prognostic ability of the core gene signature was determined through time-dependent receiver operating characteristic (ROC), Kaplan-Meier survival curve, Oncomine databases, and UALCAN databases. In addition, the prognostic value of core genes was verified in proliferation assays. We identified 217 common differentially expressed genes (DEGs) in the present study, with 101 upregulated and 138 downregulated genes. The top genes were obtained from the PPI network (protein-protein interaction). A unique six-gene signature (containing GAPDH, CDH2, BIRC5, NEK2, IDH2, and MELK) was developed for DCIS prognostic prediction. Centered on the Cancer Genome Atlas (TCGA) cohort, the ROC curve showed strong results in prognosis prediction. The six core gene signatures is often overexpressed in DCIS, with a weak prognosis. Furthermore, when breast cancer cells are transfected with small interfering RNAs, downregulation of core gene expression substantially inhibits cell proliferation, revealing a high potential for employing core genes in DCIS prognosis. In conclusion, the current investigation verified the six core genes signatures for prospective DCIS biomarkers, which may aid clinical decision-making for individual care.

Pyroptosis-Related Signatures for Predicting Prognosis in Breast Cancer.

BACKGROUND: Female breast cancer (BC) has become the most common cancer in the world, and its mortality was considerably higher in transitioning vs. transitioned countries. Pyroptosis, an inflammation-dependent programmed cell death mediated by inflammasomes, has been observed in human colorectal tumors and gliomas. However, the characteristics of pyrolysis-related genes and their influence and mechanism on the tumorigenesis and progress of BC were unknown. METHODS: Based on the global public database, we used comprehensive bioinformatics analysis to systematically analyze the expression of pyroptosis-related genes in BC and their relationship in tumor progression. In addition, BC patients were divided into two groups, and the clinical features and outcomes could be better predicted by the consistent clustering of pyroptosis-related genes. Least absolute shrinkage and selection operator (LASSO) Cox regression analysis was used to establish a risk score. Then, we further explored the prognostic value and clinical features of pyroptosis genes. Finally, we used the Human Protein Atlas (HPA) platform to identify the expression at protein levels of the key genes. RESULTS: We confirmed that the expression of pyroptosis-related genes was different in BC and normal breast tissues. A high frequency of somatic mutations occurred in BC. In addition, 33 pyroptosis-related proteins interacted frequently. Based on univariate analysis and the LASSO Cox model, five pyroptosis-related genes [including GADMA, interleukin-6 (IL-6), NLR pyrin domain-containing protein 6 (NLRP6), caspase-1 (CASP1), and caspase-9 (CASP9)], were obtained to calculate a risk score. The risk score was identified as an independent risk factor for the prognosis of BC and might play an auxiliary role in clinical classification. The HPA platform confirmed that the expression trends of the key genes were consistent with our previous studies. CONCLUSION: Pyroptosis had an important effect on the progression of BC. And the pyroptosis-related genes could be used as new prognostic biomarkers and therapeutic targets for BC.

Impact of Marital Status on Prognosis of Patients With Invasive Breast Cancer: A Population-Based Study Using SEER Database.

Objective: This study aimed to investigate the prognostic roles of marital status in patients with invasive breast cancer. Method: We extracted the data of patients with invasive breast cancer who were diagnosed during 2010-2015 and had complete staging and molecular typing from the Surveillance, Epidemiology, and End Results (SEER)-18 database. Kaplan-Meier curve method and Cox regression analysis were performed to investigate the differences in breast cancer-specific survival (BCSS) and overall survival (OS) in the total population and various subgroups with different marital statuses. Results: Among the 324,062 patients with breast cancer in this study, 55.0%, 40.0%, and 5.0% were married, unmarried, and unknown, respectively; 51.8%, 32.2%, 10.5%, and 5.5% were patients with Stages I, II, III, and IV breast cancer, respectively. The 5-year BCSS and OS of married patients were 92.6% and 88.1%, respectively, higher than those of unmarried patients (88.3% and 78.1%, P < 0.001). After adjustment for sex, age, T and N stages, histological grade, insurance status, race, year of diagnosis, and molecular subtypes, married status was an independent predictor of better BCSS [hazard ratio (HR) = 0.775, 95% confidence interval (CI) = 0.753-0.797, P < 0.001) and OS (HR = 0.667, 95% CI = 0.653-0.681, P < 0.001). After multivariate analysis of various subgroups of sex, age, stage, histological grade, insurance status, race, and molecular subtype, married status was an independent predictor of better BCSS in all subgroups except for Grade IV, age < 35 years, and uninsured subgroups. Marital status was an independent predictor of better OS in all subgroups except the subgroup with age <35 years. Conclusions: In conclusion, marital status was an independent prognostic factor for breast cancer. The unmarried patients with breast cancer had a worse prognosis, except for the subgroup with age <35 years. Hence, unmarried patients with breast cancer and age ≥35 years may need additional psychosocial and emotional support to achieve more prolonged survival, besides active treatment of primary disease.

Neoadjuvant Efficacy of Three Targeted Therapy Strategies for HER2-Positive Breast Cancer Based on the Same Chemotherapy Regimen.

(1) Background: The objective of our study was to provide evidence for choosing the optimal neoadjuvant therapy strategies for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. Three neoadjuvant targeted therapy strategies (H + Py, trastuzumab plus pyrotinib; H, trastuzumab; HP, trastuzumab plus pertuzumab) based on the same chemotherapy regimen (TC, docetaxel and carboplatin) were included in the present study; (2) Methods: We retrospectively analyzed patients with HER2-positive breast cancer who were treated with neoadjuvant TCH + Py, TCH or TCHP, followed by surgery. The outcome was the pathological complete response (pCR) rate; (3) Results: In total, 545 patients were enrolled. The pCR rate was 55.6% (35/63) in the TCH + Py cohort, 32.7% (93/284) in the TCH cohort, and 56.6% (112/198) in the TCHP cohort. The multivariate analysis showed that patients who received TCH had less possibility to achieve pCR than those who received TCH + Py (odds ratio (OR) = 0.334, 95% confidence interval (CI): 0.181−0.619, p < 0.001), while patients who received TCHP had comparable possibility to those who received TCH + Py (OR = 1.043, 95%CI: 0.554−1.964, p = 0.896); (4) Conclusions: TCH + Py provides a better pCR rate compared with TCH, and a comparable pCR rate with TCHP among patients with HER2-positive breast cancer in the neoadjuvant setting. The present study supports a novel potential treatment option for these patients. Further studies need to be explored in the future.

Essential amino acid metabolism-related molecular classification in triple-negative breast cancer.

Aim: To develop an approach to characterize and classify triple-negative breast cancer (TNBC) tumors based upon their essential amino acid (EAA) metabolic activity. Methods: We performed bioinformatic analyses of genomic, transcriptomic and clinical data in an integrated cohort of 740 TNBC patients from public databases. Results: Based on EAA metabolism-related gene expression patterns, two TNBC subtypes were identified with distinct prognoses and genomic alterations. Patients exhibiting an upregulated EAA metabolism phenotype were more prone to chemoresistance but also expressed higher levels of immune checkpoint genes and may be better candidates for immune checkpoint inhibitor therapy. Conclusion: Metabolic classification based upon EAA profiles offers a novel biological insight into previously established TNBC subtypes and advances current understanding of TNBC's metabolic heterogeneity.

Lay abstract Breast cancer is the most common malignancy in women. Triple-negative breast cancer (TNBC) is a highly malignant subtype of breast cancer, accounting for about 12­17% of total breast cancer cases. This subtype is prone to liver and bone metastases, has a high risk of recurrence and carries a poor prognosis. In this study the authors explored the essential amino acid metabolism characteristics of TNBC tumors. They found that TNBC tumors exhibiting high essential amino acid metabolism were more malignant, associated with a worse prognosis and less sensitive to chemotherapy, but were also associated with better patient responses to immunotherapy. These results offer new insights into the precision treatment of TNBC. The results of the study are promising but require additional investigation.

Development of a predictive model utilizing the neutrophil to lymphocyte ratio to predict neoadjuvant chemotherapy efficacy in early breast cancer patients.

Neutrophils and lymphocytes are key regulators of breast cancer (BC) development and progression. Neutrophil to lymphocyte ratio (NLR) values have been found to offer clear prognostic utility when evaluating BC patients. In this study, we sought to determine whether BC patient baseline NLR values are correlated with pathological complete response (pCR) following neoadjuvant chemotherapy (NCT) treatment. In total, 346 BC patients underwent NCT at our hospital from January 1, 2014 to October 31, 2019, and data pertaining to these patients were retrospectively analyzed. Correlations between clinicopathological characteristics and pCR rates were assessed via multivariate logistic regression analyses. A predictive scoring model was used to gauge the likelihood of pCR based upon regression coefficient (ß) values for each significant variable identified through these analyses. NLR cut-off values suitable for identifying patients likely to achieve pCR following NCT treatment were calculated using receiver operating characteristic (ROC) curves. All patients in the present study were females with a median age of 48 years old (range 22-77). An optimal NLR cut-off value of 1.695 was identified and was associated with respective sensitivity and specificity values of 63.6% and 45.5%. We found that higher NLR values were significantly associated with younger age, premenopausal status, and non-pCR status. Logistic regression analyses indicated that NLR, tumor size, hormone receptor (HR) status, and Ki-67 expression were all independent predictors of pCR. The area under the curve (AUC) for the resultant predictive scoring model was 0.705, and this model was assessed via K-fold cross-validation (k = 10) and bootstrapping validation, yielding respective AUC values of 0.68 and 0.694. Moreover, the incorporation of NLR into this predictive model incrementally improved its overall prognostic value relative to that of a model not incorporating NLR (AUC = 0.674). BC patients with a lower baseline NLR are more likely to exhibit pCR following NCT treatment, indicating that NLR may be a valuable biomarker for BC patient prognostic evaluation and treatment planning. Overall, our results demonstrate that this NLR-based predictive model can efficiently predict NCT efficacy in early BC patients with a high degree of accuracy.

The effectiveness of axillary reverse mapping in preventing breast cancer-related lymphedema: a meta-analysis based on randomized controlled trials.

BACKGROUND: Here, we carried out an extensive meta-analysis to investigate the effectiveness of the use of axillary reverse mapping (ARM) during axillary lymph node dissection (ALND) in preventing breast cancer-related lymphedema (BCRL). METHODS: Database searches to identify relevant randomized controlled trials (RCTs) were performed of MEDLINE (PubMed), Web of Science, Embase, and the Cochrane Library. Eligible articles with a publication date from database establishment to December 2020 were retrieved by combining keywords including: "breast cancer", "breast carcinoma", "breast neoplasm", "axillary reverse mapping", "axillary lymph node dissection", "lymphatic arm drainage", and "lymphedema". Independent data extraction was conducted, and Review Manager (version 5.3) was used for statistical analyses. RESULTS: Five eligible RCTs were included in the meta-analysis. A total of 37 patients suffered arm lymphedema (37/786, 4.71%) in the experimental group (ARM during ALND), compared with 164 arm lymphedemas (164/873, 18.79%) in the control group (ALND alone). The results showed that ARM during ALND was superior to ALND alone in reducing the incidence of BCRL [OR =0.20, 95% confidence intervals (CI): 0.13-0.29, P<0.00001]; however, the 2 procedures did not differ significantly in terms of oncological safety or shoulder movement (OR =0.30, 95% CI: 0.03-2.96, P=0.30; OR =0.44, 95% CI: 0.14-1.40, P=0.17). CONCLUSIONS: ARM during ALND can prevent and reduce the occurrence of BCRL in patients with early-stage BC during long-term follow-up. Due to the limited number of RCTs available, more in-depth, high-quality RCTs are urgently needed to provide a reliable and convincing basis for the application of ARM during ALND.

Analysis of the expression profile of serum exosomal lncRNA in breast cancer patients.

BACKGROUND: Breast cancer (BC) is a common tumor that seriously affects women's physical/mental health and even life. BC invasion and metastasis are still the main causes of mortality in BC patients. Exosomal long non-coding RNAs (exo-lncRNA) play an important role in cell communication and can help to understand better the physiological and pathological conditions that result from BC. This study investigates new potential targets and functions of the expression profiles of exo-lncRNAs in BC patients through high-throughput screening and bioinformatics. METHODS: Samples were collected from two BC patients and one healthy subject. The serum exosomal RNAs were subsequently purified, and a library was established for quality inspection and sequencing. The resultant data was compared with the reference data to obtain the differential expression of exo-lncRNAs, and predict the target genes. To obtain the final results, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to annotate the function and pathway of the differentially expressed genes. RESULTS: After a comprehensive comparison of the BC patients and healthy subjects, we discovered five up-regulated exo-lncRNAs and six down-regulated exo-lncRNAs of interest. Combining our results with a literature review and screening, we found that VIM-AS1, SNHG8, and ELDR play a role in the progression of BC, with VIM-AS1 predicting 35 target miRNAs; SNHG8 predicting 12 target miRNAs, and ELDR predicting 24 target miRNAs. Target prediction considered that the target gene of VIM-AS1 was VIM and that the target gene of SNHG8 was PRSS12. GO enrichment analysis showed that VIM mainly played a role in cell processes, biological regulation, metabolic regulation, and molecular adhesion, while PRSS12 was enriched through cell metabolism, catalytic activity, and hydrolase activity. KEGG pathway enrichment results also indicated how the VIM protein functions in cancer development through the viral infection signaling pathway and miRNA signaling pathway. CONCLUSIONS: There is a significant difference in the expression profiles of serum exo-lncRNAs between BC patients and healthy individuals. This may be closely related to BC's occurrence, development, and metastasis, and therefore provides a theoretical basis for more in-depth studies into exo-lncRNA.

Establishment and Verification of a Predictive Model for Node Pathological Complete Response After Neoadjuvant Chemotherapy for Initial Node Positive Early Breast Cancer.

OBJECTIVE: Axillary node status after neoadjuvant chemotherapy (NCT) in early breast cancer patients influences the axillary surgical staging procedure. This study was conducted for the identification of the likelihood of patients being node pathological complete response (pCR) post NCT. We aimed to recognize patients most likely to benefit from sentinel lymph node biopsy (SLNB) following NCT and to reduce the risk of missed detection of positive lymph nodes through the construction and validation of a clinical preoperative scoring prediction model. METHODS: The existing data (from March 2010 to December 2018) of the Chinese Society of Clinical Oncology Breast Cancer Database (CSCO-BC) was used to evaluate the independent related factors of node pCR after NCT by Binary Logistic Regression analysis. A predictive model was established according to the score of considerable factors to identify ypN0. Model performance was confirmed in a cohort of NCT patients treated between January 2019 and December 2019 in Henan Cancer Hospital, and model discrimination was evaluated via assessing the area under the receiver operating characteristic (ROC) curve (AUC). RESULTS: Multivariate regression analysis showed that the node stage before chemotherapy, the expression level of Ki-67, biologic subtype, and breast pCR were all independent related factors of ypN0 after chemotherapy. According to the transformation and summation of odds ratio (OR) values of each variable, the scoring system model was constructed with a total score of 1-5. The AUC for the ROC curves was 0.715 and 0.770 for the training and the validation set accordingly. CONCLUSIONS: A model was established and verified for predicting ypN0 after chemotherapy in newly diagnosed cN+ patients and the model had good accuracy and efficacy. The underlined effective model can suggest axillary surgical planning, and reduce the risk of missing positive lymph nodes by SLNB after NCT. It has great value for identifying initial cN+ patients who are more appropriate for SLNB post-chemotherapy.

Diagnostic Performance of Digital Breast Tomosynthesis for Breast Suspicious Calcifications From Various Populations: A Comparison With Full-field Digital Mammography.

The diagnostic performance difference between digital breast tomosynthesis (DBT) and conventional full-field digital mammography (FFDM) for breast suspicious calcifications from various populations is unclear. The objective of this study is to determine whether DBT exhibits the diagnostic advantage for breast suspicious calcifications from various populations compared with FFDM. Three hundred and five patients were enrolled (of which seven patients with bilateral lesions) and 312 breasts images were retrospectively analyzed by three radiologists independently. The postoperative pathology of breast calcifications was the gold standard. Breast cancer was diagnosed utilizing DBT and FFDM with sensitivities of 92.9% and 88.8%, specificities of 87.9% and 75.2%, positive predictive values of 77.8% and 62.1%, negative predictive values of 96.4% and 93.6%, respectively. DBT exhibited significantly higher diagnostic accuracy for benign calcifications compared with FFDM (87.9% vs 75.2%), and no advantage in the diagnosis of malignant calcifications. DBT diagnostic accuracy was notably higher than FFDM in premenopausal (88.4% vs 78.8%), postmenopausal (90.2% vs 77.2%), and dense breast cases (89.4% vs 81.9%). There was no significant difference in non-dense breast cases. In our study, DBT exhibited a superior advantage in dense breasts and benign calcifications cases compared to FFDM, while no advantage was observed in non-dense breasts or malignant calcifications cases. Thus, in the breast cancer screening for young women with dense breasts, DBT may be recommended for accurate diagnosis. Our findings may assist the clinicians in applying the optimal techniques for different patients and provide a theoretical basis for the update of breast cancer screening guideline.