Epidermal Growth Factor Receptor Research Articles

Overtreatment and Undertreatment of Early-Stage Breast Cancer in Older Women: Evaluating the POWER Trial

IntroductionRadiation therapy (RT) omission is acceptable in older women with early-stage estrogen receptor + breast cancer treated with breast-conserving surgery (BCS) and adjuvant endocrine therapy (AET). However, RT rates in this population remain high, causing concern for overtreatment. Conversely, patients who omit RT and do not complete a course of AET are at risk of undertreatment. In the Pre-Operative Window of Endocrine Therapy to Inform Radiation Therapy Decisions (POWER) trial, participants receive 90 days of preoperative endocrine therapy to assess tolerance before deciding about RT. This study aimed to determine the rates of undertreatment and overtreatment institutionally and among POWER trial participants. MethodsData were retrospectively collected from medical records of women aged ≥ 65 years diagnosed with invasive, estrogen receptor +/human epidermal growth factor receptor 2- breast cancer, ≤ 3 cm, who had BCS between 2012 and 2022. Patients were categorized as undertreated (BCS alone), overtreated (BCS + RT + AET), or appropriately treated (BCS + RT or BCS + AET). ResultsThe cohort included 478 patients, of whom 62 (12.97%) were undertreated, 202 (42.26%) were overtreated, and 214 (44.77%) were appropriately treated. Appropriately treated patients were more likely to be aged 70-79 years (P < 0.0001) and have high health literacy (P = 0.0003). Of the 37 patients (7.71%) in the POWER trial, more were appropriately treated than patients not in the POWER trial (81.1% versus 44.8%) (P < 0.0001). ConclusionsDespite long-standing guideline changes, RT utilization remains high. This study highlights how a novel patient-centered approach to guide adjuvant therapy decisions may increase the number of appropriately treated patients.

HER4 is a high-affinity dimerization partner for all EGFR/HER/ErbB family proteins.

Human epidermal growth factor receptors (HER)-also known as EGFR or ErbB receptors-are a subfamily of receptor tyrosine kinases (RTKs) that play crucial roles in cell growth, division, and differentiation. HER4 (ErbB4) is the least studied member of this family, partly because its expression is lower in later stages of development. Recent work has suggested that HER4 can play a role in metastasis by regulating cell migration and invasiveness; however, unlike EGFR and HER2, the precise role that HER4 plays in tumorigenesis is still unresolved. Early work on HER family proteins suggested that there are direct interactions between the four members, but to date, there has been no single study of all four receptors in the same cell line with the same biophysical method. Here, we quantitatively measure the degree of association between HER4 and the other HER family proteins in live cells with a time-resolved fluorescence technique called pulsed interleaved excitation fluorescence cross-correlation spectroscopy (PIE-FCCS). PIE-FCCS is sensitive to the oligomerization state of membrane proteins in live cells, while simultaneously measuring single-cell protein expression levels and diffusion coefficients. Our PIE-FCCS results demonstrate that HER4 interacts directly with all HER family members in the cell plasma membrane. The interaction between HER4 and other HER family members intensified in the presence of a HER4-specific ligand. Our work suggests that HER4 is a preferred dimerization partner for all HER family proteins, even in the absence of ligands.

Corrigendum to: Executive summary of the American Radium Society appropriate use criteria for brain metastases in epidermal growth factor receptor mutated-mutated and ALK-fusion non-small cell lung cancer

Corrigendum to: Executive summary of the American Radium Society appropriate use criteria for brain metastases in epidermal growth factor receptor mutated-mutated and ALK-fusion non-small cell lung cancer

Analytical and Clinical Validation of the Oncomine Dx Target Test to Assess HER2 Mutation Status in Tumor Tissue Samples From Patients With Non–Small Cell Lung Cancer Treated With Trastuzumab Deruxtecan in the DESTINY-Lung01 and DESTINY-Lung02 Studies

Context.— Trastuzumab deruxtecan (T-DXd), a human epidermal growth factor receptor 2 (HER2)–targeted therapy, has demonstrated durable anticancer activity in patients with advanced, metastatic HER2 (also known as ERBB2)–mutant (HER2m) non–small cell lung cancer (NSCLC) who have limited treatment options and poor prognosis. Objective.— To analytically validate and assess the clinical utility of the Oncomine Dx Target (ODxT) Test as a companion diagnostic to identify patients with HER2m NSCLC. Design.— Tumor samples from patients in DESTINY-Lung01 and DESTINY-Lung02 were retrospectively analyzed alongside commercially procured samples using the ODxT test and compared to the assays used for screening in these clinical trials. Results.— Positive percent agreement (PPA) and negative percent agreement (NPA) between the ODxT Test and TruSight Tumor 170 assay when testing DESTINY-Lung01 and commercially procured samples met prespecified thresholds (PPA and NPA ≥90%) for analytical accuracy (100% and 99.1%). The ODxT Test results were highly concordant with clinical trial assays (CTAs) used in DESTINY-Lung01 (PPA and NPA, 98.0% and 100%) and DESTINY-Lung02 (PPA and NPA, 96.7% and 100%) to identify activating HER2 mutations in tumor samples. Confirmed objective response rates were similar between patients with HER2m tumors identified by the ODxT Test and by CTAs in DESTINY-Lung01 (58.3% and 54.9%) and DESTINY-Lung02 (53.6% and 53.8%). Response duration was 12.0 and 9.3 months for patients identified by the ODxT Test and CTAs, respectively, in DESTINY-Lung01. Conclusions.— The ODxT Test detected HER2 mutations in NSCLC with high analytical and clinical accuracy and identified HER2m populations with response rates similar to populations identified by CTAs, supporting clinical utility of the ODxT Test to inform treatment decisions for HER2m NSCLC.

Repurposing Antiviral Drugs as Potential Anti-EGFR Agents in NSCLC: A Structure-Based Screening and Molecular Dynamics Analysis.

One of the problems resulting from recurrent hyperactivated or mutant epidermal growth factor receptors (EGFR) in non-small cell lung cancer (NSCLC) is therapeutic resistance. Consequently, this leads to increased expressionof oncogenicproteins and reduces the efficacy of EGFR tyrosine kinase inhibitors (TKIs). This study assessed antiviral drug efficacy as potential anti-EGFR agentsfor NSCLC. We used structure-based virtual screening to evaluate 66 antiviral drugs thoroughly. The top 6 antiviral drugs exhibiting impressive binding energies (i.e. surpassing a threshold of -8.5 kcalmol-1) were identified. Subsequent bioactivity analysis and ADMET profiling were performed to select the most promising candidates, followed by a molecular dynamic simulation. Among the selected antiviral regimens, dolutegravir demonstrated the highest docking score (-9.8 kcalmol-1), followed by rilpivirine and ensitrelvir, surpassing other candidates and our reference EGFR TKI. Further molecular dynamics simulations revealed promising dynamic interactions of dolutegravir, ensitrelvir, and rilpivirine with the EGFR target as compared with afatinib. Our findings highlight the repositioning potential of antiviral drugs for anti-EGFR drug discovery, supported by their robust docking scores, ADMET profiles, dynamic interactions, and binding free energies. The results open up new avenues for advanced NSCLC therapy. Further in vitro investigations are warranted to evaluate their efficacy and safety.

PEARL: A Phase Ib/II Biomarker Study of Adding Radiation Therapy to Pembrolizumab Before Neoadjuvant Chemotherapy in Human Epidermal Growth Factor Receptor 2–Negative Breast Cancer

PURPOSE To assess safety and immune biomarkers after preoperative radiation therapy (RT) and anti-PD1 therapy in breast cancer. MATERIALS AND METHODS A phase I/IIb trial of pembrolizumab with RT was conducted in patients with triple-negative breast cancer (TNBC) and hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) breast cancer. All received pembrolizumab followed by a second cycle + RT (anti-PD1/RT) of 24 Gy/three daily fractions delivered to the breast tumor and then neoadjuvant chemotherapy (NAC). Blood and tumor biopsies were obtained at baseline, after anti-PD1, and after anti–PD-RT. Coprimary end points were safety and change in tumor-infiltrating lymphocytes (TILs). Secondary end points were pathologic complete response (pCR), residual cancer burden (RCB) rates, and event-free survival (EFS). RESULTS Sixty-six patients with stage I-III breast cancer (54 TNBC, 12 HR+/HER2–) were enrolled. The median follow-up was 32 months. Safety end point was met. Incidence of grade ≥3 toxicities was 41%. The pCR rate was 59.2%, 33.3%, and 54.5% for the TNBC, HR+/HER2–, and entire cohort, respectively. A total of 77.8% of TNBC and 41.6% of HR+/HER2– had a near pCR (RCB 0-1). The 3-year EFS was 80%. In the entire cohort, PD-L1 expression increased after anti-PD1 (median Combined Positive Score [CPS], 7.49-23.20; 95% CI, –41.88 to –6.30; P = .044) and anti-PD1/RT (median CPS, 7.49-23.41; 95% CI, –41.88 to –6.30; P = .009), compared with baseline. In TNBC, adding RT to anti-PD1 significantly decreased TILs (28.9%-17.1%; 95% CI, 2.46 to 21.09; P = .014). Baseline TILs correlated with PD-L1 expression and TNF-a. CONCLUSION Preoperative RT with pembrolizumab is safe and results in high pCR rates and 3-year EFS, despite the lack of pembrolizumab during NAC. PD-L1 and TILs may be predictive biomarkers for preoperative anti-PD1/RT response. Reduction in TILs after adding RT to anti-PD1 highlights the importance of treatment sequencing.

EGFRVIII and EGFR targeted chimeric antigen receptor T cell therapy in glioblastoma

Glioblastoma is the most common primary brain tumor. Although there have been significant advances in surgical techniques, chemo and immunotherapies, and radiation therapy, outcomes continue to be devastating for these patients with minimal improvements in survival. Chimeric antigen receptor T cell therapy is a revolutionary approach that is a new pillar in the treatment of cancer. CAR T cell therapy has produced remarkable results in hematological malignancies; however, multiple limitations currently prevent it from being a first-line therapy, especially for solid tumors. Epidermal growth factor receptor is classically amplified in glioblastoma, and a variant, EGFR variant III, is expressed on glioblastoma, making it an exciting potential target for CAR T cell therapy. Although preclinical has exciting potential, clinical data has been heterogeneous. In this review, we assess the state of field of EGFR-targeted CAR T cells.

Proteogenomic characterization identifies clinical subgroups in EGFR and ALK wild-type never-smoker lung adenocarcinoma

AbstractPatients with lung adenocarcinoma who have never smoked (NSLA) and lack key driver mutations, such as those in the EGFR and ALK genes, face limited options for targeted therapies. They also tend to have poorer outcomes with immune checkpoint inhibitors than lung cancer patients who have a history of smoking. The proteogenomic profile of nonsmoking lung adenocarcinoma patients without these oncogenic driver mutations is poorly understood, which complicates the precise molecular classification of these cancers and highlights a significant area of unmet clinical need. This study analyzed the genome, transcriptome, and LC‒MS/MS-TMT-driven proteome data of tumors obtained from 99 Korean never-smoker lung adenocarcinoma patients. NSLA tumors without EGFR or ALK driver oncogenes were classified into four proteogenomic subgroups: proliferation, angiogenesis, immune, and metabolism subgroups. These 4 molecular subgroups were strongly associated with distinct clinical outcomes. The proliferation and angiogenesis subtypes were associated with a poorer prognosis, while the immune subtype was associated with the most favorable outcome, which was validated in an external lung cancer dataset. Genomic-wide impacts were analyzed, and significant correlations were found between copy number alterations and both the transcriptome and proteome for several genes, with enrichment in the ERBB, neurotrophin, insulin, and MAPK signaling pathways. Proteogenomic analyses suggested several targetable genes and proteins, including CDKs and ATR, as potential therapeutic targets in the proliferation subgroup. Upregulated cytokines, such as CCL5 and CXCL13, in the immune subgroup may serve as potential targets for combination immunotherapy. Our comprehensive proteogenomic analysis revealed the molecular subtypes of EGFR- and ALK-wild-type NSLA with significant unmet clinical needs.

The Correlation between Immunohistochemistry and In Situ Hybridization for the Assessment of Human Epidermal Growth Factor Receptor 2 (HER-2) Status in Breast Cancer in Buddhasothorn Hospital

The Correlation between Immunohistochemistry and In Situ Hybridization for the Assessment of Human Epidermal Growth Factor Receptor 2 (HER-2) Status in Breast Cancer in Buddhasothorn Hospital

Reduction of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant infection by blocking the epidermal growth factor receptor (EGFR) pathway.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants presents challenges in global efforts to transition from the pandemic to an endemic stage. The spike protein of the SARS-CoV-2 virus, which is pivotal for cell entry, exhibits significant mutations in its variants, potentially affecting infectivity and therapeutic efficacy. Recent findings indicate upregulation of the epidermal growth factor receptor (EGFR) pathway, a key target in cancer therapy, by the spike protein of SARS-CoV-2. This study aimed to investigate the activity of the EGFR pathway against SARS-CoV-2 variants and to assess the inhibitory effects of EGFR inhibitors using SARS-CoV variant pseudoviral particles to guide future therapeutic strategies. Omicron variant SARS-CoV pseudoviral particles exhibited heightened infectivity in human angiotensin-converting enzyme 2 (hACE2)-expressing HEK293 and A549 lung cancer cells accompanied by increased EGFR pathway activation in infected cells. Using the EGFR tyrosine kinase inhibitor, osimertinib, we observed a reduction in viral infection rates in hACE2-HEK293 and A549 cells infected with the SARS-CoV-2 variant pseudoviral particles. We conducted further experiments to confirm that the reduction in infection efficacy with osimertinib treatment was not associated to a decrease in cell viability. Furthermore, this inhibitory effect of osimertinib in cell lines was corroborated in a spheroid cell culture model derived from hACE2-A549 cells. These findings suggest the potential application of EGFR-targeted antiviral therapy against highly infectious SARS-CoV-2 variants.IMPORTANCEThe emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is concerning as vaccines designed for one variant need not essentially protect against other novel variants. Therefore, there is an urgent need to identify therapies that can act against multiple novel variants that have heightened virulence compared with the wild type. It has been reported that the spike protein of the SARS-CoV-2 virus elicits an increased expression of the epidermal growth factor receptor (EGFR) pathway. We used this information and examined whether treatment with an EGFR inhibitor, osimertinib, which is already approved for clinical use in cancer therapy, can reduce the infection caused by SARS-CoV-2, wild type, and Omicron and Delta variants, in two cell lines and one spheroid model. The results showed that osimertinib treatment successfully reduced infection efficacy, particularly in variants, and that this effect was not related to a reduction in cell viability, making this a promising strategy for treating SARS-CoV-2 infections.

Analysis of clinicopathological characteristics and prognostic factors in 54 metaplastic breast carcinoma patients from northwest China

Objective: Metaplastic breast carcinoma (MBC) is a special type of morphologically heterogeneous and aggressively invasive breast cancer. MBC is characterized by the transformation of tumor epithelium into squamous epithelium and/or mesenchymal components, including differentiation into spindle cells, chondrocytes, and osteocytes. Due to its rarity and invasiveness, there is a paucity of research on MBC prognosis. Furthermore, there are currently no treatment guidelines for MBC. This study analyzed the clinicopathological characteristics, immunophenotype, and prognostic features of MBC. Our aim was to better characterize MBC, thereby identifying potential prognostic factors and new treatment methods. Moreover, we also describe an MBC case treated experimentally with anti-vascular targeted therapy. Material and Methods: We retrospectively analyzed clinical pathological data on 54 female patients with MBC from Shaanxi Provincial People’s Hospital and the XiJing Hospital of Air Force Medical University. These cases were diagnosed with MBC between January 1st, 2013, and October 1st, 2018. All patients were from the northwest region of China. The gross morphological, histological, and immunohistochemical features of MBC were analyzed. Kaplan–Meier analysis was used to calculate the survival rate, and univariate analysis was performed to identify significant prognostic factors. In addition, the treatment of an MBC patient with anti-angiogenic therapy was described, and a relevant literature review was conducted. Results: MBC was diagnosed in 32 left breasts and 22 right breasts from 54 women aged 21–76 years (median age of 57 years). The maximum tumor diameter ranged from 0.6 to 14 cm (average of 4.1 cm). Of the 54 patients, 47 underwent surgical treatment, with lymph node metastasis found in 17.0% (8/47). According to the World Health Organization classification criteria for breast tumors, the study cohort consisted of 15 cases of squamous cell carcinoma, ten cases of spindle cell carcinoma, nine cases of carcinoma with associated stromal differentiation, 18 cases of mixed carcinoma, and two cases of adenocarcinoma with squamous differentiation. Based on the American Joint Committee on Cancer clinical staging criteria, the patients were classified as Stage I (10 cases, 18.5%), Stage II (26 cases, 48.1%), Stage III (11 cases, 20.4%), and Stage IV (7 cases, 13.0%). Immunohistochemical analysis revealed that 94.4% of patients had triple-negative breast cancer (TNBC), 47 cases showed mutant tumor protein 53 (TP53) expression, 29 cases showed positive epidermal growth factor receptor (EGFR) expression, 43 cases showed positive E-cadherin expression, and 37 cases showed positive Cluster of Differentiation 24 expression. The Ki-67 index ranged from 20% to 90%. Univariate analysis showed that the Ki-67 index was not significantly associated with either progression-free survival (PFS) or overall survival (OS) in MBC patients. Patients with negative axillary lymph nodes had significantly better PFS and OS than those with positive nodes (P &lt; 0.05), and patients with clinical stage I-II disease had better PFS and OS than those with stage III-IV disease (P &lt; 0.05). Patients treated with anthracycline-containing chemotherapy had significantly better PFS than those who did not receive chemotherapy. Univariate analysis revealed that the high expression of EGFR correlated with worse PFS (P &lt; 0.05). The type of surgical approach employed did not affect the prognosis of MBC patients. Following the application of anti-angiogenic therapy, a rapid partial response was observed in an MBC patient with carcinoma and associated stromal differentiation. This patient subsequently underwent surgery and radiation therapy and has now achieved over 6 years of PFS. Conclusion: MBC is a heterogeneous group of tumors with high malignancy and poor prognosis. The large majority is TNBC and exhibits unique immune phenotypes. The poor PFS of MBC patients may be related to EGFR expression, which could become a potential therapeutic target in these patients. Surgery remains the primary treatment method for MBC. The present study found that sentinel lymph node biopsy was feasible in appropriate patients, and that chemotherapy regimens incorporating anthracycline-class drugs did not appear to improve OS. Anti-angiogenic therapy holds promise as a potentially effective treatment approach for MBC, and the optimization of systemic treatment strategies should be a priority in the management of these patients.

WISP1 and Macrophage Migration Inhibitory Factor in Respiratory Inflammation: Novel Insights and Therapeutic Potentials for Asthma and COPD

Recent advancements highlight the intricate interplay between the extracellular matrix (ECM) and immune responses, notably in respiratory diseases such as asthma and Chronic Obstructive Pulmonary Disease (COPD). The ECM, a dynamic structural framework within tissues, orches-trates a plethora of cellular processes, including immune cell behavior and tissue repair mecha-nisms. WNT1-inducible-signaling pathway protein 1 (WISP1), a key ECM regulator, controls immune cell behavior, cytokine production, and tissue repair by modulating integrins, PI3K, Akt, β-catenin, and mTOR signaling pathways. WISP1 also induces macrophage migration inhibitory factor (MIF) expression via Src kinases and epidermal growth factor receptor (EGFR) activation. MIF, through its wide range of activities, enhances inflammation and tissue restructuring. Rec-ognized for its versatile roles in regulating the immune system, MIF interacts with multiple immune components, such as the NLRP3 inflammasome, thereby sustaining inflammatory pro-cesses. The WISP1–MIF axis potentially unveils complex molecular mechanisms governing im-mune responses and inflammation. Understanding the intricate roles of WISP1 and MIF in the pathogenesis of chronic respiratory diseases such as asthma and COPD could lead to the identi-fication of novel targets for therapeutic intervention to alleviate disease severity and enhance patient outcomes.

Detection of Circulating Tumor Cells and EGFR Mutation in Pulmonary Vein and Arterial Blood of Lung Cancer Patients Using a Newly Developed Immunocytology-Based Platform

Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are powerful molecular targeted therapeutic agents for lung cancer. We recently developed an original immunocytology and glass slide-based circulating tumor cell (CTC) detection platform for both CTC enumeration and EGFR mutation analysis with DNA extracted from CTCs. Methods: Using this platform, we conducted a pilot clinical study for CTC enumeration in peripheral blood (PB), pulmonary arterial blood (PA), and pulmonary venous blood (PV) from 33 patients with lung cancer (Stage I–III) who underwent surgery, followed by digital PCR-based EGFR mutation analysis of CTCs in PV from 12 patients. Results: The results showed that CTC levels were significantly higher in PV and PA than in PB (p &lt; 0.05, p &lt; 0.01. respectively), with a notably greater number of small and large CTC clusters (p &lt; 0.01). Genetic analysis of EGFR mutations of CTCs from PV (n = 12) revealed six mutations, including three Exon19del and three L856R, in CTCs and eight EGFR mutations, including five Exon19del and three L856R, in lung tumor tissue. CTC mutation status matched that of tissue samples in nine patients, was unmatched in two patients, and controversial in one patient, indicating a sensitivity of 0.75 (6/8) and specificity of 1.0 (4/4) with some false-negative results for the mutation analysis of CTCs. Conclusions: This immunocytology-based CTC detection platform is a convenient method for detecting both CTC number and EGFR mutation status under microscopy, suggesting its potential as a liquid biopsy tool in the hospital for patients with lung cancer in some clinical settings.

EGFR-TKI combined with radiotherapy in 105 patients of lung adenocarcinoma with brain metastasis: a retrospective study of prognostic factors analysis.

This study aimed to retrospectively analyze the response and prognosis factors for patients of lung adenocarcinoma with brain metastasis and epidermal growth factor receptor (EGFR) mutation, who were treated by EGFR-tyrosine kinase inhibitor (TKI) combined with brain radiotherapy (RT). From Jan 2021 to Jan 2024, the clinicopathological data of lung adenocarcinoma patients were collected from the First Affiliated Hospital of Hebei North University. SPSS version 26.0 statistical software was used for statistical analysis. P &lt; 0.05 was determined to be statistically significant. 105 patients were included. The 1, 2, 3-year overall survival (OS) rate was 82.9%, 61.2%, and 33.7%, respectively. 1, 2 ,3-year progression-free survival 1 (PFS1) rate was 62.7%, 36.6%, 22.1%. 1,2,3-year PFS2 rate was 80.8%, 54.6%, and 31.4%. The median OS, PFS1 and PFS2 was 29.8, 18.0 and 28.1 months, respectively. The COX multivariate analysis showed that gene mutation status and brain radiation dose were independent prognostic factors for OS; Gene mutation status, brain radiation dose, and response evaluation to initial treatment (response evaluation) are independent prognostic factors for PFS1; Clinical stage, gene mutation status, brain radiation dose, and response evaluation are independent prognostic factors for PFS2. TKI combined with brain radiotherapy is effective on lung adenocarcinoma patients with EGFR mutation and brain metastasis. Patients with 19 Del or 21 L858R mutation and brain radiation doses ≥ 40 Gy have longer OS, PFS1, and PFS2, and complete remission (CR) + partial remission (PR) is associated with longer PFS1 and PFS2, Patients in stage IVA have longer PFS2.

The Factors Associated With Mutant Epidermal Growth Factor Receptor Positivity in Patients With Lung Cancer: A Study From a Tertiary Care Center in Pakistan

The Factors Associated With Mutant Epidermal Growth Factor Receptor Positivity in Patients With Lung Cancer: A Study From a Tertiary Care Center in Pakistan

Ultrasound-based radiomics nomogram for predicting HER2-low expression breast cancer

PurposeAccurate preoperative identification of Human epidermal growth factor receptor 2 (HER2) low expression breast cancer (BC) is critical for clinical decision-making. Our aim was to use machine learning methods to develop and validate an ultrasound-based radiomics nomogram for predicting HER2-low expression in BC.MethodsIn this retrospective study, 222 patients (108 HER2-0 expression and 114 HER2-low expression) with BC were included. The enrolled patients were randomly divided into a training cohort and a test cohort with a ratio of 8:2. The tumor region of interest was manually delineated from ultrasound image, and radiomics features were subsequently extracted. The features underwent dimension reduction using the least absolute shrinkage and selection operator (LASSO) algorithm, and rad-score were calculated. Five machine learning algorithms were applied for training, and the algorithm demonstrating the best performance was selected to construct a radiomics (USR) model. Clinical risk factors were integrated with rad-score to construct the prediction model, and a nomogram was plotted. The performance of the nomogram was assessed using receiver operating characteristic curve and decision curve analysis.ResultsA total of 480 radiomics features were extracted, out of which 11 were screened out. The majority of the extracted features were wavelet features. Subsequently, the USR model was established, and rad-scores were computed. The nomogram, incorporating rad-score, tumor shape, border, and microcalcification, achieved the best performance in both the training cohort (AUC 0.89; 95%CI 0.836-0.936) and the test cohort (AUC 0.84; 95%CI 0.722-0.958), outperforming both the USR model and clinical model. The calibration curves showed satisfactory consistency, and DCA confirmed the clinical utility of the nomogram.ConclusionThe nomogram model based on ultrasound radiomics exhibited high prediction value for HER2-low BC.

Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Cancer: Current Use and Future Prospects

Tyrosine kinase inhibitors (TKIs) have emerged as a leading targeted cancer therapy, reducing the side effects often seen with non-targeted treatments, especially the damage to healthy cells. To tackle resistance, typically caused by epidermal growth factor receptor (EGFR) mutations, four generations of TKIs have been developed. Each generation has shown improved effectiveness and fewer side effects, resulting in better patient outcomes. For example, patients on gefitinib, a first-generation TKI, experienced a progression-free survival (PFS) of 10 months compared to 5 months with conventional chemotherapy. Second-generation TKI afatinib outperformed erlotinib and extended PFS to 11.1 months compared to 6.9 months with cisplatin. Third-generation TKIs further increased survival to 38.6 months, compared to 31.8 months with first-generation TKIs. This progress demonstrates the ability of newer TKIs to overcome resistance, particularly the T790M mutation, while reducing adverse effects. Ongoing research focuses on overcoming resistance from newer mutations like C797S to further improve patient survival. These developments highlight the significant progress in TKI therapy and the continued effort to refine cancer treatment. Recent research in South Korea shows that third-generation TKIs are ineffective against non-small cell lung cancer (NSCLC) with the C797S mutation. Several trials have started showing promising in vitro and in vivo results, but more trials are needed before clinical approval. This review underscores notable advancements in the field of EGFR TKIs, offering a comprehensive analysis of their mechanisms of action and the progression of various TKI generations in response to resistance.

Racial Differences in Breast Cancer Survival Between Black and White Women According to Tumor Subtype: A Systematic Review and Meta-Analysis.

Despite effective early-detection approaches and innovative treatments, Black women in the United States have higher breast cancer mortality rates compared with White women. The purpose of this systematic review and meta-analysis is to determine the extent of disparities in breast cancer survival between Black and White women according to tumor subtype. A comprehensive database search was performed for full-text, English-language articles published from January 1, 2000, to December 31, 2022. Included studies compared survival between Black and White female patients with breast cancer within subtypes defined by hormone receptor and human epidermal growth factor receptor 2 (HER2)/neu (HER2; now known as ERBB2) status. Random-effects models were used to combine study-specific results and generate pooled relative risks (RRs) and 95% CIs for breast cancer-specific or overall survival (OS). A protocol for this review was registered in PROSPERO (CRD42021268212). Eighteen studies including 228,885 (34,262 Black; 182,466 White) patients with breast cancer were identified. Compared with White women, Black women had a higher risk of breast cancer death for all tumor subtypes. The summary risk of breast cancer death was 50% higher among hormone receptor-positive HER2-negative [HER2-] tumors (RR, 1.50 [95% CI, 1.30 to 1.72]), 34% higher for hormone receptor+/HER2+ (RR, 1.34 [95% CI, 1.10 to 1.64]), 20% higher for hormone receptor-negative (-)/HER2+ (RR, 1.29 [95% CI, 1.00 to 1.43]), and 17% higher among individuals with hormone receptor-/HER2- tumors (hazard ratio, 1.17; 95% CI, 1.10 to 1.25). Black women also had poorer OS than White women for all subtypes. These results suggest there are both subtype-specific and subtype-independent mechanisms that contribute to disparities in breast cancer survival between Black and White women, which require multilevel interventions to address and achieve health equity.

Molecular Testing for EGFR Mutation in Moroccan NSCLC Patients: CHU Hassan II-Fez Experience.

Epidermal growth factor receptor (EGFR) mutation screening in non-small cell lung cancer (NSCLC) is now used to guide treatment decisions to identify patients with EGFR positive mutations that predict response to EGFR tyrosine kinase inhibitors. This study aimed to explore with a prospective study the current testing practices and the predictive value of EGFR mutations in a series of 261 patients with NSCLC. EGFR mutation testing was conducted using 2 different assays: bidirectional Sanger sequencing of polymerase chain reaction (PCR) and real-time PCR on the Rotor-Gene Q instrument. Epidermal growth factor receptor mutation testing was performed for 261 patients with lung cancer. Exons 18 to 21 were successfully analyzed in 113 tumors by Direct sequencing and in 148 tumors by real-time PCR. The prevalence of positive EGFR-mutations in each method was 22.1% (N = 25) and 24.3% (N = 36), respectively (P = .3). In total, EGFR mutations were detected in 59 patients among 261 patients with NSCLC. A statistically significant association between female sex, nonsmoking history, nonsolid major pattern, and a higher EGFR mutation frequency. In this study, we investigated clinicopathological differences between tumors harboring exon 19del and those harboring L858R. We did not find any significant differences between the 2 mutations and gender or smoking features, interestingly, the prevalence of patients aged >60 years was significantly higher in the L858R group than in the exon 19del group (81.8% vs 55.8%, P = .05). A significant association was observed between exon 19 deletions and the papillary major pattern, but no correlation was detected between exon 21 mutation and any histological pattern. This prospective study documented the real-world clinical testing of EGFR mutation in Moroccan NSCLC patients. Our experience confirms the need to develop standards-based guidelines for the routine performance and evaluation of EGFR testing to improve clinical care for this subset of lung cancer. On the other hand, our study demonstrated that tumors with exon 19 deletions and L858R harbor specific clinicopathological features in NSCLC.

Immunotherapy plus chemotherapy for patients with EGFR-mutated non-squamous cell lung cancer for disease progression after EGFR tyrosine-kinase inhibitor: A meta-analysis of randomized controlled trials.

Patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations face poor outcomes after progression on tyrosine kinase inhibitors (TKIs). The efficacy of immune checkpoint inhibitors (ICIs) combined with chemotherapy in these patients remains uncertain. We searched for studies published between randomized controlled trials of ICIs in combination therapies in advanced NSCLC patients post EGFR TKI progression. Data on progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were extracted and analyzed. Six studies with a total of 2,225 patients were analyzed. The pooled hazard ratio (HR) for PFS was 0.60 (95% CI, 0.55 - 0.65; P &lt; 0.0001), indicating a significant improvement in PFS with ICIs. Subgroup analysis suggested that patients with prior exposure to third-generation TKIs showed a more pronounced benefit (HR = 0.61; 95% CI, 0.49 - 0.76; P &lt; 0.0001). However, no benefit was found in patients without prior exposure. The efficacy of the experimental interventions was also shown on the pooled estimates of OS (HR = 0.87; 95% CI, 0.77 - 0.0.99; P value = 0.04) and ORR (OR = 1.91; 95% CI, 1.32 - 2.76; P &lt;0.0001). ICIs may significantly benefit PFS among patients with EGFR-mutated NSCLC who have progressed on TKI treatment. Future research should continue stratifying patients based on prior treatment exposure to optimize therapeutic strategies.