Human Epidermal Growth Factor Receptor Research Articles

National trends and survival outcomes associated with non-guideline-concordant treatment of inflammatory breast cancer.

National Comprehensive Cancer Network (NCCN) guidelines for inflammatory breast cancer (IBC) recommend trimodal therapy: neoadjuvant chemotherapy, modified radical mastectomy (MRM), and adjuvant radiation therapy. Historically, a minority received NCCN-guideline-concordant trimodal therapy (GCT). We explored factors associated with non-concordance, types of non-concordance, and the association of GCT with survival. The National Cancer Database (NCDB) was analyzed for patients with non-metastatic IBC who underwent surgery from 2006 to 2019. Multivariate logistic regression identified factors associated with GCT. Cox proportional hazard models assessed the impact of GCT, and components of non-concordance, on mortality. Of 13,733 patients, 47.6% received GCT. Of non-GCT patients, 39.7% had mixed non-concordance, 25.5% exclusive chemotherapy non-concordance, 24.0% exclusive radiation non-concordance, and 10.8% exclusive surgical non-concordance. A higher burden of comorbidities, node-negative disease, and positive human epidermal growth factor receptor 2 (HER2) and hormone receptor status were associated with reduced odds of receiving GCT. GCT was associated with reduced 3-(hazard ratio [HR] = 0.83, 95% CI 0.73-0.95) and 5-year (HR = 0.83, 95% CI 0.76-0.91) mortality. Chemotherapy non-concordance and mixed non-concordance were associated with higher three-(HR = 1.28, 95% CI 1.07-1.53; HR = 1.20, 95% CI 1.01-1.43 respectively) and 5-year (HR = 1.42, 95% CI 1.26-1.60; HR = 1.17, 95% CI 1.03-1.33) mortality. Radiation non-concordance was associated with increased hazard of 1-year mortality (HR = 3.03, 95% CI 1.75-5.23). Exclusive surgical non-concordance was not associated with survival; however, simple mastectomy portended a higher hazard of 5-year mortality (HR = 1.26, 95% CI 1.08-1.46). Despite improved survival, a minority of patients received GCT. Omitting neoadjuvant chemotherapy or adjuvant radiation was associated with reduced survival, whereas surgical non-concordance in patients with concordant chemoradiation did not impact survival. Simple mastectomy was associated with reduced survival, supporting the rationale for axillary lymphadenectomy.

Identification of Potential Anticancer Phytochemicals of Piper chaba by Comprehensive Molecular Docking, Molecular Dynamics Simulation and In-Vitro Studies.

Human colon cancer and prostate cancer are the most common malignancy globally. Despite the availability of many treatments, resistance to traditional medicines, such as chemotherapy and radiotherapy, remains a severe obstacle in cancer treatment. Hence, searching for new therapeutic options is of utmost priority. The present investigation evaluates the in-silico and in-vitro anticancer potential of phytochemicals of Piper chaba. The cytotoxicity results demonstrated that the plant extract exhibited significant anticancer activity, with IC50 values of 12.66 ± 0.25µg/mL for HCT-116 and 19.49 ± 0.37µg/mL for DU-145. Molecular docking and molecular dynamics simulations were performed to explore the interaction of potential drug targets with the phytochemicals. Subsequently, pharmacokinetic parameters calculations were performed to evaluate the drug-likeness. Piperine exhibits the highest binding affinity for vascular endothelial growth factor receptor-2 (VEGFR2) protein with a docking score of -9.71kcal/mol. Sylvatine had a greater binding affinity for human epidermal growth factor receptor 3 (HER3) protein than the other phytochemicals. Isopiperine, chabamide, Piperlonguminine, Santamarine and Versalide only exhibited ligand activity for human IKK beta protein (inhibitor of kappa B kinase). Additionally, a principal component analysis was performed to strengthen the investigation's scope. These proposed phytochemicals are reported to possess potential VEGFR2, HER2 and human IKK beta inhibition. The best phytochemical hits have excellent binding affinity and hold a massive anticancer potential, opening up new avenues for prospective future investigations in cancer treatment.

Background Parenchymal Enhancement in Breast MRI Correlates with Molecular Subtypes of Breast Cancer.

MRI could be considered as a non-destructive disease diagnosis procedure, this procedure does not allow directly molecular types of cancer. Herein, we aimed to evaluate the correlation of breast MRI background parenchymal enhancement (BPE) and fibroglandular tissue (FGT) with the molecular subtypes and immunohistochemical markers of breast cancer. This was a single-cross-sectional retrospective study.Fifty-six patients diagnosed with unilateral breast cancer who underwent breast MRI scans before needle biopsy or surgery were selected. The relationship between qualitative and quantitative BPE/FGT ratios and the expression of breast cancer molecular subtypes and immunohistochemical markers were evaluated in patients with breast cancer. Quantitative BPE (BPE%) of luminal A and luminal B was significantly lower than that of triple-negative breast cancer. There was no significant difference in the qualitative BPE/FGT between the different breast cancer subtypes. The quantitative BPE (BPE%) of estrogen receptor (ER)- negative tumors was higher than that of the ER-positive tumors, and the expression of FGT%, BPE%, and other immunohistochemical markers (human epidermal growth factor receptor-2(HER-2), progesterone receptor (PR), and Ki-67) were not significantly different. The proportion of high BPE distribution in HER-2 positive tumors was higher than that in the HER-2 negative group; however, there was no significant difference in the expression of qualitative BPE/FGT and other immunohistochemical markers (ER, PR, and Ki-67). There were significant differences in the levels of BPE among the different molecular subtypes. Therefore, BPE may be a potential imaging biomarker for the diagnosis of the molecular subtypes of breast cancer.

Molecular Docking and Pharmacological In Silico Evaluation of Camptothecin and Related Ligands as Promising HER2-Targeted Therapies for Breast Cancer

Breast cancer is one of the leading causes of cancer-related mortality in women worldwide, highlighting the importance of effective therapies. This study evaluates the interaction between camptothecin, a potent anticancer agent, and two key receptors implicated in breast cancer progression: HER2 (human epidermal growth factor receptor 2) and EGFR (epidermal growth factor receptor), using molecular docking. The results reveal a stronger binding affinity between camptothecin and HER2 than EGFR, in contrast to neratinib, which demonstrated affinity exclusively for HER2. Camptothecin exhibits significant hydrophobic and pi-alkyl interactions with HER2, whereas its interactions with EGFR are primarily mediated by hydrogen bonds. Molecular dynamics (MD) simulations of the camptothecin-HER2 complex indicate stable binding, with minimal fluctuations observed over 100 nanoseconds, confirming the stability of the ligand–receptor interaction. Pharmacokinetic evaluations, based on Lipinski’s rule of five, demonstrate that camptothecin adheres to essential drug-likeness parameters, suggesting favorable bioavailability. Furthermore, the analysis comparing the pharmacological properties of camptothecin with other well-known anticancer compounds, such as neratinib, shows that camptothecin exhibited superior compliance with drug-likeness rules. Despite its low solubility, the binding stability and pharmacokinetic profile suggest its potential as an effective therapeutic agent for breast cancer, particularly when combined with drug delivery systems that enhance solubility. This work underscores the importance of receptor-specific ligand interactions in drug design and highlights the need for further studies into camptothecin’s clinical applications, especially in HER2-positive breast cancer treatment.

Three-dimensional turbo-spin-echo amide proton transfer-weighted and intravoxel incoherent motion imaging mri for triple-negative breast cancer: a comparison with molecular subtypes and histological grades

ObjectiveTo investigate associations between breast cancer molecular subtype and intravoxel incoherent motion imaging (IVIM) and amide proton transfer-weighted (APTw).MethodsThis prospective study involved 264 patients with suspected breast tumors who underwent both breast APTw and IVIM MRI. The maximum diameter of the tumor (Dmax), APT value, apparent diffusion coefficient (ADC), diffusion coefficient (D), pseudo diffusion coefficient (D*), and perfusion fraction (f) values along with histological subtype, grade, and prognostic factors (Ki-67, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2), were compared. APT values about biological subtypes, Ki-67 labeling index, and nuclear grades (NGs) were further analyzed.ResultsA total of 205 participants (mean age, 53 years, range 29–80) were included in the evaluation. The triple-negative breast cancer (TNBC) cancers showed significantly higher D* values than the Luminal B cancers (P = 0.002), while there was no difference in Dmax, ADC, D, and APT (P = 0.068,0.318,0.432,0.089). The TN-type cancers showed significantly higher APT values than the HER2-type cancers (P = 0.002). The area under the curve (AUC) obtained from APTw, IVIM, and Dmax was 0.874. The APT had a moderate positive correlation with the unclear grade (r = 0.473, P < 0.001), and the D* had a weak positive correlation with the Ki-67 labeling index(r = 0.160, P = 0.022).ConclusionThe TN subtype of breast cancer is associated with APT value and D* from IVIM. The APTw may be a promising method for predicting TNBC molecular subtypes.

Lin28/let-7 axis in breast cancer.

Let-7 microRNAs are tumor suppressor microRNAs, and their reduced expression frequently occurs in various types of cancers, including breast cancer. A notable correlation exists between decreased let-7 microRNA levels and the overexpression of Lin28A and Lin28B, particularly in breast cancer cases with poor prognoses. Dysregulation of Wnt signaling significantly contributes to the upregulation of Lin28A and Lin28B in breast cancer. Both Lin28A and Lin28B operate from different cellular compartments to inhibit the biogenesis of let-7 microRNAs, which are essential for the post-transcriptional regulation of genes involved in key cellular functions such as proliferation, differentiation, and apoptosis. Decreased expression of let-7 microRNAs leads to the overexpression of oncogenes such as K-ras, C-myc, and SOX-2 in breast cancer. Overexpression of Lin28A associated with reduced let-7 microRNA levels is observed in estrogen receptor positive, estrogen receptor negative, and human epidermal growth factor receptor 2 positive breast cancers, whereas Lin28B overexpression with reduced let-7 microRNA levels occurs specifically in triple negative breast cancer. This review aims to dissect the molecular interplay between Lin28A, Lin28B, and let-7 microRNAs, elucidating their roles in breast carcinogenesis, metastasis, and the development of resistance to conventional treatments like radiation and chemotherapy. Additionally, the review addresses potential therapeutic avenues offered by let-7 microRNAs or their mimics, as well as Lin28A and Lin28B inhibitors, in the treatment of breast cancer.

First-Line Tislelizumab Plus Chemotherapy for Advanced Gastric Cancer with Programmed Death-Ligand 1 Expression≥1%: A Retrospective Analysis of RATIONALE-305.

Tislelizumab plus investigator-chosen chemotherapy (ICC) demonstrated a statistically significantimprovement in overall survival (OS) versus placebo plus ICC in RATIONALE-305 in patients with locallyadvancedunresectableor metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric cancer/gastroesophageal junction cancer (GC/GEJC) in the intent-to-treat population and in patients with programmed death-ligand 1 (PD-L1) Tumor Area Positivity (TAP) score≥5%. The United States Food and Drug Administration Oncologic Drugs Advisory Committee voted (September 2024) against first-line treatment with programmed cell death protein-1 inhibitors in this setting in patients with a PD-L1 combined positive score<1 or TAP score<1%, due to an unfavorable benefit-risk profile. Thus, we retrospectively analyzed data from RATIONALE-305 in patients with a PD-L1 TAP score≥1%. Adult patients with locally advanced unresectable or metastatic HER2-negative GC/GEJC were randomized to tislelizumab 200 mg or placebo with ICC every 3 weeks. Efficacy and safety outcomes of tislelizumab plus ICC versus placebo plus ICC were retrospectively assessed in those with a PD-L1 TAP score≥1%. At the final analysis cutoff (February 28, 2023), 432 patients received tislelizumab plus ICC and 453 received placebo plus ICC, and had a PD-L1 TAP score≥1%. Clinically meaningful improvements to OS were observed with tislelizumab plus ICC compared with placebo plus ICC [15.0months (95% confidence interval[CI] 13.3-16.7) vs. 12.8 months(95% CI12.1-14.1), respectively; stratified hazard ratio 0.77 (95% CI 0.67-0.90)]. Progression-free survival, overall response rate, duration of response, and disease control rate, were also improved. OS improvements were maintained at a 3-year data cutoff (February 28, 2024). Tislelizumab plus ICC had an acceptable safety profile with no new safety signals. Tislelizumab plus ICC is an effective and tolerable first-line treatment for patients with locally advanced unresectable or metastatic HER2-negative GC/GEJC with a PD-L1 TAP score≥1%. NCT03777657.

Insight into the inhibitory activity of mangiferin and Silybin against HER2 and EGFR using theoretical and experimental approaches

Despite the advances made in diagnosing and treating breast cancer, it continues to pose a significant threat to women’s health. High-risk mutations can lead to high resistance to current treatments and poor prognosis. Therefore, new treatment strategies are needed. Mangiferin and silybin, two natural substances obtained from plants, have demonstrated encouraging results as anticancer drugs. This study investigated the activity of these compounds against two therapeutic targets, human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR). We assessed the binding affinity and stability of these compounds with the active sites of wild-type and mutated HER2 and EGFR by using computational screening techniques, namely molecular docking, density functional theory, and molecular dynamics (MD) simulations with the MMGBSA method. We used molecular docking, triplicate MD simulations summing 300 ns each, and density functional theory analysis to estimate the binding mechanism of mangiferin and silybin inside the wild-type and mutated EGFR and HER2 active regions. Moreover, an in vitro experiment showed that mangiferin and silybin inhibited the growth of two HER2-positive breast cancer cell lines, BT-474 and SK-BR-3, at micromolar concentrations. These findings suggest the potential for developing novel anticancer therapies that specifically target EGFR and HER2.

Male Breast Cancer in Portugal: A Descriptive Analysis of a 20-Year Cohort.

Male breast cancer (MBC) is a rare malignancy, representing less than 1% of all breast cancer cases. Despite the rising incidence, MBC research remains limited, with most data extrapolated from female breast cancer (FBC). This study evaluated the clinicopathological features, treatment strategies, and survival outcomes of MBC patients in Portugal over two decades. A retrospective analysis of MBC cases from the Portuguese National Oncology registry (2001-2021) was conducted. Clinicopathological features, therapeutic strategies, and overall survival (OS) were assessed across three disease categories: localized, locally advanced, and metastatic. Hormone receptor status, human epidermal growth factor receptor 2 (HER2) expression, and Ki-67 index were recorded, and survival was estimated using Kaplan-Meier methods. A total of 620 MBC cases were included with median age at diagnosis 68 years (interquartile range: 60-77). Localized disease accounted for 60.3% of the cases, locally advanced for 24.5%, and metastatic 15.2%. Most tumours were invasive carcinoma of no special type (86%), and hormone receptor-positive (estrogen receptor: 96.6%; progesterone receptor: 85.6%). HER2 -disease was noted in 11.6% of cases and triple-negative in 1.6%. Mastectomy was the primary surgical intervention while tamoxifen was the most widely used adjuvant endocrine therapy-exemestane therapy (A-ET). ET was the most prescribed first-line therapy. Median OS was 86 months for localized, 70 months for locally advanced, and 41 months for metastatic disease. This study highlights the unique challenges of MBC, including late-stage diagnoses and reliance on FBC-derived protocols. Findings suggest an urgent need for male-specific clinical trials and molecular research to optimise treatment and outcome. In Portugal increased awareness and early detection initiatives will be important to advance MBC care.

Real-Life Efficacy of Palbociclib and Ribociclib in Advanced Breast Cancer

Background: Clinical trials in metastatic hormone receptor-positive (HR+) human epidermal growth factor receptor-2 (HER2)-negative patients have shown that cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors both increase response rates and provide survival benefits. The efficacy of these therapies needs to be supported by real-life data. In this study, we aimed to evaluate treatment response, survival and affecting factors in patients with HR+/HER2− metastatic breast cancer (MBC) who were followed up with CDK 4/6 inhibitors in our center. Materials and methods: A retrospective analysis of 120 patients with HR+/HER2− MBC treated with ribociclib or palbociclib in combination with letrozole or fulvestrant was performed. Results: Median progression-free survival (mPFS) was 24 months in the general population, 27 months in the ribociclib arm and 20 months in the palbociclib arm, with no significant difference in progression-free survival (PFS) in both arms (p = 0.25). The mPFS was longer in the ribociclib + letrozole arm compared to palbociclib + letrozole (27 vs. 20 months, respectively). PFS was also longer in patients receiving ribociclib + fulvestrant compared to palbociclib + fulvestrant but not statistically significant (33 vs. 21 months, respectively). Median overall survival (mOS) was not reached, but 3-year overall survival (OS) was statistically significantly longer in the ribociclib arm (87% vs. 55.5%, respectively, p = 0.03). Conclusion: Palbociclib and ribociclib are first-line treatment options for metastatic HR+/HER2− disease and have similar efficacy. In our study, while the mPFS was not statistically significant in both arms, the 3-year OS rate was higher in the ribociclib arm and statistically significant. Our findings were confirmed in randomized studies comparing both agents head-to-head.

Serum HER2 as potential prognostic biomarker in primary breast cancer patients

Tissue expressed human epidermal growth factor receptor 2 (HER2) is an established parameter of breast cancer, and it is determined in routine clinical practice by histology. This study aims to assess the prognostic value of serum HER2 protein quantified using ELISA in 66 primary breast cancer patients. The median follow-up period was 94 months. Prognostic performance was assessed through receiver operating characteristic (ROC), Cox proportional hazards regression, and Kaplan-Meier analyses. There was a significant difference between serum HER2 levels of patients with and without recurrence. Prognostic associations were significant for age, grade, nodal status, follicle-stimulating hormone, oestradiol, and serum HER2. The cut-off point for serum HER2 levels was 6.0 ng/mL. Recurrence incidence was 29% in the serum HER2 high subgroup, compared to only 10% in the serum HER2 low subgroup. Serum HER2 testing by ELISA holds promise as an additional tool alongside routine tissue HER2 analysis for primary breast cancer patients.

Fabrication of Bioconjugates Clacked Chitosan-Coated SN-38 Liposomal Nanoparticles: Improved Precise Chemotherapy Efficacy in Lung Cancer Cells and Its Apoptosis.

Employing an active targeting method with monoclonal antibodies for chemotherapeutics-loaded nanocarriers represents a promising option to enhance the specific drug delivery and alleviate the detrimental effects of chemotherapeutic agents. Targeted delivery to the human epidermal growth factor receptor-2 (HER2), which is overexpressed in HER2+ lung cancerous cells, can be accomplished by conjugating nanoparticles with a monoclonal antibody (anti-HER2). We developed trastuzumab (TZ)-conjugated chitosan iodoacetamide (CsIA)-coated liposomal nanoparticles carrying SN-38 (TZ-SN-CsIA LNPs) as a lung-targeted delivery. CsIA was used to develop trastuzumab-clacked nanoparticles (TZ LNPs). The structure, physicochemical characteristics, SN-38 encapsulation, SN-38 release, and anticancer properties of the LNPs were established. The TZ LNPs were spherical, measuring around 77nm in diameter, and exhibited a positive zeta potential; upon drug incorporation, the diameter of the TZ LNPs enlarged. A sustained, 24-h SN-38 release from the nanocarriers was accomplished. TZ LNPs demonstrated substantial cellular accumulation and markedly enhanced anticancer efficacy against HER2+ Calu-3 lung adenocarcinoma cancer cells compared to the drug solution and unconjugated LNPs. Consequently, TZ-SN-CsIA LNPs may be a potential nanocarrier for HER2+ lung cancer.

The Diagnostics of Disease Relapse Within Five-Year Follow-Up and the Role of Androgen Receptor Expression in Patients with Early Triple-Negative Breast Cancer

Background/Objectives: Triple-negative breast cancer (TNBC) is characterized by the absence of the expression of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2. As there are no specific targeted therapies, TNBC patients often face an aggressive clinical course. The expression of the androgen receptor (AR) has been found in up to 30% of TNBC cases, but the association between the AR status and survival rates in TNBC remains controversial. The aim of this study was to explore the association of AR expression with the disease outcome in patients with early TNBC within a 5-year follow-up. Methods: AR expression was determined by immunohistochemistry in a cohort of 124 early-TNBC patients treated at the Institute for Oncology and Radiology of Serbia. The cut-off value used for the positive AR status was &gt;10% tumor cells. The association of the AR status with clinicopathological factors (age, stage, tumor diameter, lymph node invasion, metastatic spread, Ki-67 score, EGFR score, and cytokeratin 5/6 score) and the disease outcome (disease-free survival—DFS—and overall survival—OS) was investigated. Results: Our analysis showed that the AR-positive status was associated with a significantly lower Ki-67 score compared to the AR-negative samples. A univariate analysis indicated that the age, tumor size, nodal status, and EGFR score significantly influenced both 5-year DFS and OS. Multivariate Cox analysis suggested that a smaller tumor size, lower nodal status, and AR expression were independent predictors of longer survival rates in TNBC patients. Conclusions: The results of this study suggest that the positive AR status may be a favorable prognostic factor in TNBC patients within the first five years after surgery.

Breast Cancer Biopsies With Group 2 and Group 4 Human Epidermal Growth Factor Receptor 2 Fluorescence In Situ Hybridization Results Should Have Repeated Testing on Excision

Context.— Breast cancer with human epidermal growth factor receptor 2 (HER2) fluorescence in situ hybridization (FISH) group 2 (HER2:CEP17 ratio ≥2.0 and HER2 signals &amp;lt;4.0) and group 4 (HER2:CEP17 ratio &amp;lt;2.0 and HER2 signals ≥4.0 and &amp;lt;6.0) patterns represent a small and challenging subset of cases. These special categories were previously considered positive and equivocal, respectively. However, following the 2018 update of the American Society of Clinical Oncology/College of American Pathologists guidelines, these groups were deemed negative unless concurrent immunohistochemistry was 3+. The guidelines indicate repeated HER2 testing on excisional specimens may be appropriate, but retesting is not definitively recommended. Objective.— To determine if group 2 and group 4 cases change after repeated testing on additional specimens. Design.— A retrospective review of breast biomarker synoptic reports was conducted from 2016 to 2023. Cases identified as HER2 FISH group 2 and group 4 were recorded, along with the results of any repeated testing. Results.— A total of 5695 cases with HER2 FISH testing were identified: 101 cases of group 2 (1.8%) and 194 of group 4 (3.4%). There were 42 initial breast biopsies from group 2, and 110 from group 4 with repeated testing on excision. Of these, 5 group-2 (11.9%) and 19 group-4 (17.3%) cases became HER2 positive. None demonstrated positive staining (3+) by immunohistochemistry. There was no association with receipt of neoadjuvant therapy or triple-negative status in either group. Conclusions.— We recommend that breast biopsies with group 2 and 4 FISH results have HER2 testing repeated on the excisional specimen.

Exploration of biomarkers for the efficacy of anti-PD-1 immunotherapy in patients with gastric cancer peritoneal metastasis

Objective: To explore the prognosis of patients with gastric cancer peritoneal metastasis (PM) receiving programmed cell death-1 (PD-1) antibody therapy, and investigate the biomarkers that affect the prognosis of anti-PD-1 therapy. Methods: This restrospecific study collected the clinic-pathological data of 56 patients with peritoneal metastasis of gastric cancer who received first-line treatment in the Nanjing Drum Town Hospital from March 2020 to September 2023, among which 41 had received anti-PD-1 immunotherapy and 15 hadn't. The relationship between overall survival (OS) and anti-PD-1 immunotherapy was evaluated by Kaplan-Meier analysis. The relationship between baseline peripheral blood indicators and treatment response of patients with anti-PD-1 treatment was analyzed using unpaired t-test. Subsequently, the COX proportional risk regression model was used to explore the clinical prognostic factors that may affect anti-PD-1 immunotherapy by univariate and multivariate analysis. The clinical prognostic factors included baseline data and baseline peripheral blood indexes such as anti-PD-1 treatment lines, Eastern Cooperative Oncology Group performance status (ECOG PS), combined positive score (CPS), expression of human epidermal growth factor receptor 2 (Her-2), EBER status, pathological types, other metastatic lesions, ascites content before immunotherapy, with or without abdominal drainage during anti-PD-1 treatment, blood lipid indicators, inflammatory indicators, and tumor indicators. Results: Kaplan-Meier survival statistics showed similar OS (15.9 vs. 15.2 months, P=0.6002) in patients with anti-PD-1 therapy compared to those without anti-PD-1 therapy. Patients with baseline high-density lipoprotein (HDL) ≥0.97 mmol/L (n=22) demonstrated a significantly longer median OS compared to those with HDL<0.97 mmol/L (15.2 vs. 13.5 months; P=0.018). Similarly, the cohort with apolipoprotein A1 (ApoA1) levels ≥0.86 g/L (n=21) showed superior survival outcomes, with a median OS of 17.73 months versus 12.27 months in the ApoA1＜0.86 g/L group (n=20; P=0.006). In contrast, elevated baseline alpha-fetoprotein (AFP) levels (n=2) were associated with markedly reduced survival (median OS: 5.7 vs. 15.2 months in normal AFP group, n=37; P=0.005). Notably, elevated pretreatment ApoA1 levels correlated with enhanced immunotherapy response (P=0.038). Multivariate Cox regression analysis revealed that ApoA1 deficiency (≥0.86 g/L) independently predicted better OS following PD-1 antibody therapy (hazard ratio [HR], 0.35 [95% CI, 0.12-0.98]; P=0.046) in gastric cancer patients with PM. Conclusions: In our study, it is first proposed that ApoA1 could be a significant predictor of the survival advantages of immunotherapy in gastric cancer patients with PM.

Serum Enzymes and Pathologic Complete Response to the Addition of Targeted Therapy in Neoadjuvant Chemotherapy for HER2-Positive Breast Cancer Patients.

This study investigated the association between circulating alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), lactate dehydrogenase (LDH), and gamma-glutamyltransferase (GGT) and the pathologic complete response (pCR) in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving neoadjuvant chemotherapy with trastuzumab (H) and pertuzumab (P). Data were collected from 290 patients with HER2-positive breast cancer at Sichuan Cancer Hospital between August 2019 and August 2023. Blood samples were collected to assess the serum enzyme levels, including ALT, AST, CK, LDH, and GGT. Univariable analysis was first performed, followed by multivariable logistic regression, to assess the association of pCR with ALT, AST, CK, LDH, and GGT levels before and after neoadjuvant chemotherapy with H and P. Of the 290 patients, 174 (60%) achieved pCR after neoadjuvant chemotherapy combined with dual-target therapy. Multivariable logistic regression analysis showed that lower ALT and GGT levels, higher ALT levels before treatment (odds ratio [OR], 2.02; 95% confidence interval [CI] 1.11-3.67; p = 0.02), and higher GGT levels after treatment (OR, 2.04; 95% CI 1.14-3.66; p = 0.017) were significantly associated with pCR. Additionally, neoadjuvant chemotherapy combined with H and P dual-target therapy increased ALT, AST, LDH, and GGT levels in patients' blood. Before neoadjuvant chemotherapy combined with H and P dual-target therapy, ALT levels were associated with pCR. After the treatment, GGT levels were linked to pCR. This treatment regimen was associated with increased blood levels of ALT, AST, LDH, and GGT.

Patterns of HER2 expression and genomic correlates in lung cancer, with a focus on preanalytical variables impacting immunohistochemical staining results

AimsFam-trastuzumab deruxtecan-nxki (T-DXd) was recently approved for advanced stage or metastatic solid tumours with human epidermal growth factor receptor 2 (HER2) immunohistochemical (IHC) 3+ staining. Data on HER2 IHC testing...

Distinguishing Low Expression Levels of Human Epidermal Growth Factor Receptor 2 in Breast Cancer: Insights from Qualitative and Quantitative Magnetic Resonance Imaging Analysis

Background: The discovery of novel antibody–drug conjugates for low-expression human epidermal growth factor receptor 2 (HER2-low) breast cancer highlights the inadequacy of the conventional binary classification of HER2 status as either negative or positive. Identification of HER2-low breast cancer is crucial for selecting patients who may benefit from targeted therapies. This study aims to determine whether qualitative and quantitative magnetic resonance imaging (MRI) features can effectively reflect low-HER2-expression breast cancer. Methods: Pre-treatment breast MRI images from 232 patients with pathologically confirmed breast cancer were retrospectively analyzed. Both clinicopathologic and MRI features were recorded. Qualitative MRI features included Breast Imaging Reporting and Data System (BI-RADS) descriptors from dynamic contrast-enhanced MRI (DCE-MRI), as well as intratumoral T2 hyperintensity and peritumoral edema observed in T2-weighted imaging (T2WI). Quantitative features were derived from diffusion kurtosis imaging (DKI) using multiple b-values and included statistics such as mean, median, 5th and 95th percentiles, skewness, kurtosis, and entropy from apparent diffusion coefficient (ADC), Dapp, and Kapp histograms. Differences in clinicopathologic, qualitative, and quantitative MRI features were compared across groups, with multivariable logistic regression used to identify significant independent predictors of HER2-low breast cancer. The discriminative power of MRI features was assessed using receiver operating characteristic (ROC) curves. Results: HER2 status was categorized as HER2-zero (n = 60), HER2-low (n = 91), and HER2-overexpressed (n = 81). Clinically, estrogen receptor (ER), progesterone receptor (PR), hormone receptor (HR), and Ki-67 levels significantly differed between the HER2-low group and others (all p &lt; 0.001). In MRI analyses, intratumoral T2 hyperintensity was more prevalent in HER2-low cases (p = 0.009, p = 0.008). Mass lesions were more common in the HER2-zero group than in the HER2-low group (p = 0.038), and mass shape (p &lt; 0.001) and margin (p &lt; 0.001) significantly varied between the HER2 groups, with mass shape emerging as an independent predictive factor (HER2-low vs. HER2-zero: p = 0.010, HER2-low vs. HER2-over: p = 0.012). Qualitative MRI features demonstrated an area under the curve (AUC) of 0.763 (95% confidence interval [CI]: 0.667–0.859) for distinguishing HER2-low from HER2-zero status. Quantitative features showed distinct differences between HER2-low and HER2-overexpression groups, particularly in non-mass enhancement (NME) lesions. Combined variables achieved the highest predictive accuracy for HER2-low status, with an AUC of 0.802 (95% CI: 0.701–0.903). Conclusions: Qualitative and quantitative MRI features offer valuable insights into low-HER2-expression breast cancer. While qualitative features are more effective for mass lesions, quantitative features are more suitable for NME lesions. These findings provide a more accessible and cost-effective approach to noninvasively identifying patients who may benefit from targeted therapy.

Diversity of ER-positive and HER2-negative breast cancer stem cells attained using selective culture techniques

Breast cancer stem cells are a promising therapeutic target in cancer. We explored breast cancer stem cell diversity and establish a methodology for selectively culturing breast cancer stem cells. We collected breast cancer tissues from surgical samples of treatment-naïve patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Following isolation, cells were subjected to spheroid culture on non-adherent plates. Of the 57 cases, successful culture was achieved in 48 cases, among which the average ratio of CD44+/CD24− breast cancer cells increased from 13.8% in primary tumors to 61.6% in spheroids. A modest number of spheroid cells successfully engrafted in mice and subsequently re-differentiated within the murine environment, confirming their stemness. ER expression in spheroid cells exhibited negative conversion in 52.1% of cases. The proportion of Twist-, Snail-, and Vimentin-positive cells increased from 43.8%, 12.9%, and 7.7–75.0%, 58.1%, and 37.7%, respectively. ER-positive, HER2-negative breast cancer stem cells were classified into two groups using DNA microarrays. Gene Ontology analysis unveiled higher expression of immune response-related genes in one group and protein binding-associated genes in the other. We demonstrated stable and selective culture of breast cancer stem cells from patient-derived breast cancer tissue using spheroid cultures.

Molecular Subtypes of Breast Cancer in Arab Women: Distribution and Prognostic Insights

BackgroundUnderstanding the ethnic molecular subtype characteristics of breast cancer (BC) in Saudi women is crucial for providing comprehensive prognostic information and optimizing patient outcomes, making it essential to study their distribution and impact on survival.MethodsThis hospital-based cohort study analyzed clinic–pathological data from 1,035 Saudi women diagnosed with invasive BC and followed for 12 years, at King Faisal Specialist Hospital & Research Center. Cancers were classified into four molecular subtypes: luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, and triple-negative. Survival outcomes were assessed using Kaplan–Meier survival curves and Cox proportional hazard models.ResultsLuminal A was the most common molecular subtype (41.7%), followed by luminal B (23.4%), triple-negative (19.5%), and HER2-enriched (15.4%). Age at diagnosis, menopause, and tumor grade were significantly associated with subtypes (p < 0.05). Survival outcomes varied significantly (p = 0.0202), with luminal A and B showing the highest 5-year survival rates (~ 83%), triple-negative at 76.4% (hazard ratio: 1.55), and HER2-enriched tumors had the lowest at 69.1%, with a 1.75-fold higher risk of death. Advanced-stage cancers (III and IV) were strongly associated with increased mortality, with hazard ratios of 2.5 and 7.6, respectively, compared to early-stage disease.ConclusionsMolecular subtypes and stage at diagnosis are key predictors of mortality in Saudi women with BC. The poor outcomes for HER2-enriched and TNBC subtypes highlight the need for timely diagnosis and targeted treatments, emphasizing the importance of personalized care and addressing ethnic variations in BC diagnosis.