^
    3d
    Identification of phytomolecules as isoform and mutation specific PI3K-α inhibitor for protection against breast cancer using e-pharmacophore modeling and molecular dynamics simulations. (PubMed, BMC Chem)
    e-Pharmacophore model was generated using Receptor-Ligand complex using the Inavolisib drug (PDB:8EXV) and phase screening was performed using the Molport database of natural compounds...These compounds demonstrated favorable results in several parameters, including RMSD, RMSF, Rg, SASA, PCA, FEL, and total energy evaluations. Therefore, these compounds are projected to function as PI3K-α inhibitors and because of its natural origin it can possess fewer side effects than the conventional medicine, which should be validated by proper in vivo and in vitro models.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HER-2 negative • HER-2 mutation
    |
    Itovebi (inavolisib)
    4d
    Real-World Prevalence, Treatment Patterns, and Outcomes for Patients With HER2 (ERBB2)-Mutant Metastatic Non-Small Cell Lung Cancer, From a US-Based Clinico-Genomic Database. (PubMed, Cancer Med)
    During this study period, the most common regimens were platinum-based chemotherapy with or without ICI in first and second line, and median rwOS was 13.2 and 8.2 months, respectively. These results indicate the need for more effective targeted therapies in this patient population.
    Observational data • Retrospective data • Journal • Real-world evidence • IO biomarker • Real-world • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    EGFR mutation • HER-2 mutation
    6d
    Deep learning algorithm on H&E whole slide images to characterize TP53 alterations frequency and spatial distribution in breast cancer. (PubMed, Comput Struct Biotechnol J)
    This study underscores the potential of DL algorithms to predict key genetic alterations, such as TP53 mutations, in BC. DL-based histopathological analysis represents a valuable tool for improving patient management and tailoring treatment approaches based on molecular biomarker status.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53)
    |
    HER-2 positive • TP53 mutation • HER-2 mutation • HER-2 positive + HR negative
    9d
    Assessing the Effect of DZD9008 on the Pharmacokinetics of the Cocktail Probes Representative for CYP3A4, P-gp, BCRP and OATP1B1 in Patients with EGFR or HER2 Mutant Advanced Non-small Cell Lung Cancer (WU-KONG19) (clinicaltrials.gov)
    P1, N=25, Completed, Dizal Pharmaceuticals | Recruiting --> Completed | Trial primary completion date: Aug 2024 --> May 2024
    Trial completion • Trial primary completion date • Metastases
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
    |
    EGFR mutation • HER-2 mutation
    |
    sunvozertinib (DZD9008)
    10d
    ERBB2/ERBB3-mutated S100/SOX10-positive uterine sarcoma: something new. (PubMed, Virchows Arch)
    The authors review the sparse literature on molecular-genetic aberrations involving the epidermal growth factor receptor family of receptor tyrosine kinases (ERBB1/EGFR, ERBB2, ERBB3, and ERBB4) in uterine mesenchymal tumors, a review that suggests that such tumors may be pathologically heterogeneous. The potential clinical significance of demonstrating a targetable ERBB2/ERBB3 tyrosine kinase mutation or other EGFR family aberrations, as well as its distinctive pathologic profile, supports the segregation of the tumor reported herein as a distinct and emerging entity.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ALK (Anaplastic lymphoma kinase) • PGR (Progesterone receptor) • FGFR1 (Fibroblast growth factor receptor 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NF1 (Neurofibromin 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • ATRX (ATRX Chromatin Remodeler) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • CD34 (CD34 molecule) • NCAM1 (Neural cell adhesion molecule 1) • SOX10 (SRY-Box 10) • CD68 (CD68 Molecule) • MME (Membrane Metalloendopeptidase) • PRAME (Preferentially Expressed Antigen In Melanoma) • MLANA (Melan-A) • NTRK (Neurotrophic receptor tyrosine kinase) • PDGFB (Platelet Derived Growth Factor Subunit B) • STAT6 (Signal transducer and activator of transcription 6) • MITF (Melanocyte Inducing Transcription Factor)
    |
    EGFR mutation • HER-2 mutation • CDKN2A deletion • ATRX mutation • ERBB3 mutation • NF1 deletion
    12d
    ADELA: Elacestrant + Everolimus in Patients ER+/HER2-, ESR1mut, Advanced Breast Cancer Progressing to ET and CDK4/6i. (clinicaltrials.gov)
    P3, N=240, Recruiting, MedSIR | Not yet recruiting --> Recruiting | Initiation date: Sep 2024 --> Dec 2024
    Enrollment open • Trial initiation date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • CDK4 (Cyclin-dependent kinase 4)
    |
    HER-2 mutation • ER mutation
    |
    everolimus • dexamethasone • Orserdu (elacestrant)
    13d
    Genomic landscape of circulating tumor DNA in HER2-low metastatic breast cancer. (PubMed, Signal Transduct Target Ther)
    Additionally, among patients with ERBB2 mutations and treated with pyrotinib, the HER2-low group may experience superior prognosis when compared to the HER2-0 group...Moreover, we classified HER2-low MBC into three clusters, providing a reference for subsequent treatment with enhanced precision. Our study offers valuable insights into the biology of HER2-low MBC and may provide reference for personalized treatment strategies.
    Retrospective data • Journal • Circulating tumor DNA • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    PIK3CA mutation • HER-2 mutation
    |
    Irene (pyrotinib)
    18d
    DESTINY-Lung05: A Single Arm Phase 2 Study to Evaluate Efficacy and Safety of Trastuzumab Deruxtecan for Patients With HER2 Mutant NSCLC (clinicaltrials.gov)
    P2, N=72, Completed, AstraZeneca | Active, not recruiting --> Completed | Trial completion date: Feb 2025 --> Nov 2024
    Trial completion • Trial completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 mutation
    |
    Enhertu (fam-trastuzumab deruxtecan-nxki)
    19d
    A Clinical Trial of TG6050 in Patients With Metastatic Non-Small Cell Lung Cancer (Delivir) (clinicaltrials.gov)
    P1, N=36, Recruiting, Transgene | Trial completion date: Mar 2025 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Apr 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    BRAF V600E • KRAS mutation • KRAS G12C • BRAF V600 • HER-2 mutation • RET fusion • RET mutation • ROS1 fusion • RET rearrangement • KRAS G12
    |
    TG6050
    22d
    ERBB2 comprehensive profiling and prognostication in Stage III Colon Cancer: Findings from PETACC8 and IDEA-France cohorts. (PubMed, Gastroenterology)
    The molecular definition of ERBB2-status could represent a cost-effective alternative in stage III CC. ERBB2 alterations and low RNA expression significantly reduce TTR, highlighting the complex role of ERBB2.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 amplification • HER-2 mutation • HER-2 expression
    23d
    Targeted Sequencing of HER2-Positive Breast Cancer Mutations Revealed a Potential Association between PIK3CA and Trastuzumab Resistance. (PubMed, Asian Pac J Cancer Prev)
    PIK3CA variants were more frequent in resistant HER2+ BC patients than in responsive patients, with a significant correlation between PIK3CA mutation and a lower pCR rate. PIK3CA variants within exon 9 and 20 (such as Glu545Lys and His1047Tyr respectively) were associated with trastuzumab resistance.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HER-2 positive • HER-2 overexpression • PIK3CA mutation • HER-2 mutation • HER-2 positive + HER-2 overexpression
    |
    Herceptin (trastuzumab)
    23d
    REVERT - taRgeted thErapy for adVanced colorEctal canceR paTients (clinicaltrials.gov)
    P=N/A, N=106, Completed, University of Rome Tor Vergata | Recruiting --> Completed
    Trial completion • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene)
    |
    KRAS mutation • EGFR mutation • BRAF mutation • HER-2 mutation
    26d
    HER2-related biomarkers predict clinical outcomes with trastuzumab deruxtecan treatment in patients with HER2-expressing metastatic colorectal cancer: biomarker analyses of DESTINY-CRC01. (PubMed, Nat Commun)
    Higher levels of HER2 biomarkers in baseline tissue and liquid biopsies, including HER2 status (IHC/ISH), HER2/CEP17 ratio, HER2 ISH signals, HER2 H-score, plasma HER2 (ERBB2) amplification status, HER2 adjusted plasma copy number, and HER2 extracellular domain correlate with antitumor activity (indicated by objective response rate, progression-free survival, and overall survival) of T-DXd. Baseline circulating tumor DNA (ctDNA) analysis suggests antitumor activity of T-DXd in patients who had baseline activating RAS, PIK3CA, or HER2 mutations detected in ctDNA.
    Clinical data • Journal • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HER-2 positive • HER-2 amplification • PIK3CA mutation • HER-2 mutation • HER-2 expression
    |
    Enhertu (fam-trastuzumab deruxtecan-nxki)
    27d
    Advances in the Treatment of Rare Mutations in Non-Small Cell Lung Cancer. (PubMed, Onco Targets Ther)
    Some of these targeted therapies have already been approved by the Food and Drug Administration (FDA), and many others are currently undergoing clinical trials. This review summarizes recent advances in NSCLC treatment with molecular targets, highlighting progress, challenges, and their impact on patient prognosis.
    Review • Journal
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NRG1 (Neuregulin 1) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    KRAS mutation • EGFR mutation • KRAS G12C • BRAF mutation • HER-2 mutation • RET fusion • ALK rearrangement • RET mutation • ROS1 fusion • ROS1 rearrangement • MET mutation • NRG1 fusion • KRAS G12 • NRG1 fusion • NTRK fusion
    29d
    Strain sUrveillance during Chemotherapy for improving Cardiovascular OUtcomes measured by Magnetic Resonance Imaging (SUCCOUR-MRI) (ACTRN12620001094965)
    P=N/A, N=1100, Completed, Baker Heart and Daibetes Institute | Recruiting --> Completed
    Trial completion • MRI
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 mutation
    1m
    Response to furmonertinib in a patient with non-small cell lung cancer harboring HER2 exon 21 insertion mutation: a case report. (PubMed, Front Oncol)
    Firstly, we describe the patient's treatment history, including failed third-line combination treatments of systemic chemotherapy with bevacizumab or carrelizumab or anlotinib, primary lung tumor recurrence, bilateral lung metastases progression, and new brain metastatic lesion detection. Next, we detail the patient's fourth-line treatment with radiotherapy for brain metastases and two cycles of bevacizumab plus Abraxane and cisplatin, however, the disease progressed and relapsed...However, the patient died due to hypoproteinemia combined with severe pneumonia in December 2023. Furmonertinib may be effective for NSCLC patients with HER2 T8962A and L869R mutations and further studies are needed to confirm these results in prospective clinical trials.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    EGFR mutation • HER-2 mutation • HER-2 L869R
    |
    Avastin (bevacizumab) • cisplatin • Focus V (anlotinib) • AiRuiKa (camrelizumab) • albumin-bound paclitaxel • Ivesa (firmonertinib)
    1m
    MAP3K1 mutations confer tumor immune heterogeneity in hormone receptor-positive HER2-negative breast cancer. (PubMed, J Clin Invest)
    In preclinical models, the postbiotics tyramine could reverse the MAP3K1 mutation-induced MHC-I reduction, thereby augmenting the efficacy of immunotherapy. Collectively, our study identified the vital biomarker driving the immunological heterogeneity of HR+/HER2- breast cancer and elucidated the underlying molecular mechanisms, which provided the promise of tyramine as a novel therapeutic strategy to enhance the efficacy of immunotherapy.
    Journal • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • CD8 (cluster of differentiation 8) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • TAP1 (Transporter 1)
    |
    HER-2 positive • HR positive • HER-2 negative • HER-2 mutation • HR positive + HER-2 negative • MAP3K1 mutation • PTEN mutation + HR positive
    1m
    Simultaneous Occurrence of HER2 Mutations in EGFR Mutant NSCLC: Case Reports. (PubMed, JTO Clin Res Rep)
    HER2 mutation and amplification have been identified as distinct molecular targets in lung cancer with different therapeutic and prognostic values. The coexistence of HER2 and EGFR mutations is extremely rare, and therefore, no data exist on the best treatment in these cases.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
    |
    EGFR mutation • HER-2 amplification • HER-2 mutation
    |
    Tagrisso (osimertinib) • Gilotrif (afatinib)
    1m
    A basket study of Initumab combined with pyrrotinib and triplizumab in the treatment of HER2 variant advanced solid tumors (ChiCTR2400089182)
    P2, N=193, Not yet recruiting, Shanghai East Hospital; Shanghai East Hospital
    New P2 trial • Pan tumor • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 amplification • HER-2 mutation
    |
    Loqtorzi (toripalimab-tpzi)
    1m
    Preoperative prediction of occult lymph node metastasis in patients with non-small cell lung cancer: a simple and widely applicable model. (PubMed, BMC Pulm Med)
    The personalized scoring prediction model constructed based on multiple tumors, ERBB2 miss mutation, CA125 levels, CA153 levels, tumor site, tumor length, and serum ferritin can screen NSCLC patients who may have OLNM.
    Retrospective data • Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • MUC16 (Mucin 16, Cell Surface Associated)
    |
    HER-2 mutation • MUC16 mutation
    2ms
    NCI-2022-04099: Testing the Safety and Tolerability of the Anti-cancer Drugs Trastuzumab Deruxtecan and Neratinib for Cancers With Changes in the HER2 Gene (clinicaltrials.gov)
    P1, N=30, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended
    Trial suspension • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • CD4 (CD4 Molecule) • CASP3 (Caspase 3)
    |
    HER-2 positive • HER-2 overexpression • HER-2 amplification • HER-2 mutation • HER-2 L755S • HER-2 A775_G776insYVMA • HER-2 S310F • HER-2 V777L • HER-2 G778_P780dup • HER-2 D769Y • HER-2 L869R • HER-2 V842I • HER-2 H878Y • HER-2 L866M • HER-2 A775 • HER-2 G309A • HER-2 P780-Y781insGSP • HER-2 R678Q • HER-2 R896C • HER-2 T862A • HER-2 YVMA
    |
    Nerlynx (neratinib) • Enhertu (fam-trastuzumab deruxtecan-nxki)
    2ms
    Luminal subtype independent immune-enrichment in inflammatory breast cancer based on commercially available tumor portrait. (SABCS 2024)
    Over half of cases with luminal molecular phenotype demonstrate immune-enriched TME, suggesting a potentially significant role for immunotherapy in these patients and expanded efforts in this arena. Using the BG Tumor PortraitTM assay, low TMB and MSS was present in the majority of IBC samples evaluated in spite of numerous studies showing common DNA repair mutations. HER2 expressing cases demonstrated a predominantly immune-desert phenotype and further study of the clinical relevance and validation of this is warranted.
    Tumor mutational burden • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • RAD51B (RAD51 Paralog B) • FANCL (FA Complementation Group L)
    |
    TP53 mutation • TMB-H • HR positive • HER-2 negative • PIK3CA mutation • HER-2 mutation • HER-2 expression • PTEN mutation • ARID1A mutation • TMB-L • RAD51B mutation
    |
    Prosigna™ Breast Cancer Prognostic Gene Signature Assay • BostonGene Tumor Portrait™ Test
    2ms
    Circulating tumor DNA surveillance in ZEST, a randomized, phase 3, double-blind study of niraparib or placebo in patients w/ triple-negative breast cancer or HER2+ BRCA-mutated breast cancer with molecular residual disease after definitive therapy. (SABCS 2024)
    The ZEST study was terminated early because of infeasibility of completing enrollment due to a low rate of ctDNA+ and a high rate of metastatic disease at the time of ctDNA+. Although ctDNA testing began any time after EODT, ctDNA+ occurred most frequently on the first test and ≤6 months from EODT. Pts, predominantly those with TNBC, had a high rate of radiographic recurrence at time of ctDNA+, consistent with early recurrence typical of TNBC.
    Clinical • P3 data • BRCA Biomarker • PARP Biomarker • Circulating tumor DNA
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRCA (Breast cancer early onset)
    |
    HER-2 mutation • BRCA mutation
    |
    Signatera™
    |
    Zejula (niraparib)
    2ms
    Characteristics of ESR1-Mutant HER2 Positive Metastatic Breast Cancer (MBC) (SABCS 2024)
    Median PFS after detection of ESR1 mutation was 3.2 months (range 1.9 –30.7), with all patients receiving HER2-directed therapy and four patients receiving Fulvestrant... Patients who develop ESR1 mutations in the setting of HER2+ mBC most often had point mutations in L536, E380 and D538, and had high rates of co-mutation with PIK3CA, which may have prognostic implications. To date, clinical trials regarding ESR1 mutations in breast cancer have excluded patients with HER2+ disease. These patients should be included in future studies of ESR1-targeted therapies.
    Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • PTEN (Phosphatase and tensin homolog)
    |
    HER-2 positive • TP53 mutation • ER positive • PIK3CA mutation • HER-2 mutation • PTEN mutation • ER mutation
    |
    Guardant360® CDx
    |
    fulvestrant
    2ms
    Efficacy of trastuzumab deruxtecan (T-DXd) in patients with metastatic lobular breast cancer with or without HER2 mutations: the MSKCC experience (SABCS 2024)
    The SUMMIT trial demonstrated meaningful activity of neratinib + fulvestrant + trastuzumab in patients with HR+, HER2 non-amplified, HER2-mutant MBC. In patients with mILC and HER2 mutation, there was a trend toward longer TTP with T-DXd. Genomic data could aid in prognostication in patients with mILC treated with T-DXd. These findings warrant confirmation in larger cohorts.
    Clinical • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog)
    |
    HER-2 negative • PIK3CA mutation • HER-2 mutation • HER-2 expression • PTEN mutation • PIK3CA mutation + PTEN mutation • PIK3CA mutation + AKT1 mutation + PTEN mutation
    |
    MSK-IMPACT
    |
    Nerlynx (neratinib) • Enhertu (fam-trastuzumab deruxtecan-nxki) • fulvestrant
    2ms
    Exploratory biomarker analysis of Trastuzumab deruxtecan (T-DXd) vs Trastuzumab emtansine (T-DM1) efficacy in human epidermal growth factor receptor 2–positive (HER2+) metastatic breast cancer (mBC) in DESTINY-Breast03 (DB-03). (SABCS 2024)
    T‑DXd outperformed T‑DM1 regardless of HRD+/- or BRCA1/2 alt status, although HRD+ status and BRCA1/2 alt were poor prognosticators for PFS in both arms. Mutational analysis at DP will be presented.
    Clinical • BRCA Biomarker • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12)
    |
    HER-2 amplification • HER-2 mutation • HRD • EGFR positive
    |
    GuardantINFINITY™
    |
    Kadcyla (ado-trastuzumab emtansine) • Enhertu (fam-trastuzumab deruxtecan-nxki)
    2ms
    APOBEC3 mutagenesis induces resistance-promoting genomic alterations in breast cancer. (SABCS 2024)
    Upon exposure to the CDK4/6 inhibitor abemaciclib, these cells acquired APOBEC3-context truncating mutations in RB1 tumor suppressor gene, a well-characterized mechanism of resistance... Our work reveals that APOBEC3 mutational signatures predict poor treatment outcomes of HR+ mBC. We demonstrate that APOBEC3 mutagenesis, primarily through the enzymatic activity of A3A and A3B, drives resistance to endocrine and targeted therapies by causing APOBEC3-context resistance-associated changes. We further show that the presence of APOBEC3 mutagenesis can be detected before therapy exposure and may therefore represent a valuable biomarker and therapeutic target.
    ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • RB1 (RB Transcriptional Corepressor 1) • APOBEC3B (Apolipoprotein B MRNA Editing Enzyme Catalytic Subunit 3B) • APOB (Apolipoprotein B) • APOBEC3A (Apolipoprotein B MRNA Editing Enzyme Catalytic Subunit 3A)
    |
    ER positive • HR positive • PIK3CA mutation • HER-2 mutation • RB1 mutation
    |
    MSK-IMPACT
    |
    Verzenio (abemaciclib)
    2ms
    Tumor genomics in young patients with metastatic breast cancer (SABCS 2024)
    In EMBRACE, differences in mutational frequency of several genes were observed by age at MBC diagnosis among patients with recurrent MBC, most notably for HR+/HER2- patients. Lower OS among younger recurrent MBC patients may be driven by these differences, particularly by high frequency of TP53 mutations in this age group. Further investigation of these genes is warranted to elucidate pathways leading to metastasis and to improve survival for young MBC patients.
    Clinical • Tumor mutational burden • BRCA Biomarker • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CDH1 (Cadherin 1) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • GATA3 (GATA binding protein 3)
    |
    TP53 mutation • BRCA1 mutation • TMB-H • HER-2 negative • PIK3CA mutation • HER-2 mutation • AKT1 mutation • CDH1 mutation
    |
    OncoPanel™ Assay
    2ms
    Genomic analysis of circulating tumor DNA (ctDNA) from patients with triple-negative, HER2-mutant metastatic breast cancer treated with neratinib as monotherapy or in combination with trastuzumab in the SUMMIT trial (SABCS 2024)
    These findings were consistent with those reported for SUMMIT hormone receptor-positive (HR+) HER2-mutant mBC cohorts, in which patients treated with N or N + fulvestrant (N+F) experienced promising clinical responses but shorter DOR. Although limited by small numbers, addition of T to N in patients with HER2-mutant mTNBC, despite deepening and prolonging response, did not appear to preclude eventual emergence of either on-pathway (ERBB3) or off-pathway (KRAS, TP53) mutations. In contrast to observations in N+F+T-treated patients with HR+, HER2-mutant disease, no additional HER2 alterations were detected upon progression in N+T-treated patients with mTNBC in this small dataset. Future investigations may evaluate clinical utility of sequencing therapies targeted to mutations acquired in response to N-based therapy in patients with HER2-mutant mTNBC.
    Clinical • Combination therapy • Genomic analysis • Circulating tumor DNA • Metastases • Omic analysis
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • mTOR (Mechanistic target of rapamycin kinase)
    |
    TP53 mutation • KRAS mutation • HR positive • HER-2 amplification • HER-2 mutation • KRAS Q61H • ERBB3 mutation • MTOR mutation • HER-2 T798I • TP53 R196*
    |
    MSK-ACCESS
    |
    Herceptin (trastuzumab) • Nerlynx (neratinib) • fulvestrant
    2ms
    Rising ESR1 Mutations in Circulating Tumor DNA (ctDNA) Mediate Endocrine Therapy (ET) Resistance to Everolimus and ET but Retain Sensitivity to Fulvestrant in HR+/HER2- Metastatic Breast Cancer (MBC) (SABCS 2024)
    None of the patients received ESR1-targeted therapy with Elacestrant. Our findings indicate that the level changes of ctDNA ESR1 mutations have implications with regards to treatment sensitivity and resistance to various therapies in patients with HR+/HER2- mBC. These results suggest a potentially effective method for monitoring treatment response and guiding future therapy by providing new insights into targeting ESR1 pathways to overcome resistance.
    Circulating tumor DNA • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HER-2 negative • PIK3CA mutation • HER-2 mutation • ER mutation • ER Y537S • ER D538G • ER Y537N
    |
    Guardant360® CDx
    |
    everolimus • fulvestrant • Orserdu (elacestrant)
    2ms
    Elacestrant vs SOC in ER+, HER2- advanced or metastatic breast cancer (mBC) with ESR1-mutated tumors: ESR1 allelic frequencies and clinical activity from the phase 3 EMERALD trial (SABCS 2024)
    Elacestrant demonstrated a significant improvement in mPFS vs SOC in patients with both high and low ESR1 VAF. The clinical benefit and activity of elacestrant vs SOC was maintained regardless of type of ESR1 mutation variant and the abundance/quantity of ESR1 mutations in patients with ER+/HER2- mBC. In all patients with ER+/HER2, ESR1-mut mBC, elacestrant may replace fulvestrant-based combinations, and delay chemotherapy or ADC-based regimens.
    Clinical • P3 data • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • CDK4 (Cyclin-dependent kinase 4)
    |
    HER-2 negative • HER-2 mutation • ER mutation • ER Y537S • ER D538G • ER Y537N • ER-L
    |
    Guardant360® CDx
    |
    fulvestrant • Orserdu (elacestrant)
    2ms
    Molecular landscape of HR+/HER2- male breast cancer (MaBC) compared with female breast cancer (FeBC) (SABCS 2024)
    These data indicate that HR+/HER2- MaBC has a differential mutational spectrum and TMB-high frequency, MHC Class I and MHC class II, drug efflux and stem cell-related gene expression compared to their HR+/HER2- FeBC counterparts. These suggest important differences in tumor biology between men and women with HR+/HER2- breast cancer. A better understanding of these differences with additional research may help in design future clinical trials and treatments for men with HR+/HER2- BC.
    Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • CDH1 (Cadherin 1) • HLA-DQB1 (Major Histocompatibility Complex, Class II, DQ Beta 1) • KLF4 (Kruppel-like factor 4) • SOX2 • POU5F1 (POU Class 5 Homeobox 1) • ABCC2 (ATP Binding Cassette Subfamily C Member 2) • ALDH1A1 (Aldehyde Dehydrogenase 1 Family Member A1) • HLA-B (Major Histocompatibility Complex, Class I, B) • GATA3 (GATA binding protein 3) • PROM1 (Prominin 1) • HLA-DQB2 (Major Histocompatibility Complex, Class II, DQ Beta 2)
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    TMB-H • HR positive • MSI-H/dMMR • HER-2 negative • HER-2 mutation • HER-2 expression • EGFR positive • AR expression
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    PD-L1 IHC 22C3 pharmDx
    2ms
    Analysis of Therapeutic Efficacy and Adverse Prognostic Factors of Secondary Central Nervous System Lymphoma (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)
    HD-MTX combined with TMZ as the first-line strategy may improve patient prognosis, and early application of gene sequencing is beneficial for evaluating prognosis.
    Retrospective data • Journal
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    HER-2 (Human epidermal growth factor receptor 2) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • KMT2D (Lysine Methyltransferase 2D) • CD79B (CD79b Molecule) • PIM1 (Pim-1 Proto-Oncogene) • BTG2 (BTG Anti-Proliferation Factor 2) • TBL1XR1 (TBL1X Receptor 1)
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    HER-2 mutation • PIM1 mutation
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    methotrexate IV
    2ms
    LUNG-MAP SUB-STUDY: Targeted Treatment for Advanced Non-Small Cell Lung Cancer That Has Increased Copies of the MET Gene (An Expanded Lung-MAP Treatment Trial) (clinicaltrials.gov)
    P2, N=88, Recruiting, SWOG Cancer Research Network | Not yet recruiting --> Recruiting
    Enrollment open • Metastases
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase)
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    BRAF V600E • KRAS mutation • EGFR mutation • BRAF V600 • HER-2 mutation • MET amplification • EGFR T790M • MET exon 14 mutation • ALK fusion • ROS1 fusion • MET mutation • RET rearrangement
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    Rybrevant (amivantamab-vmjw)
    2ms
    Clinicopathologic and Genomic Features of Invasive Stratified Mucin-producing Carcinoma of the Uterine Cervix Coexisting With High-grade Squamous Intraepithelial Lesion. (PubMed, Int J Gynecol Pathol)
    No copy number-associated variants or structural variations were identified in either lesion. These results suggest that patients with ISMC may benefit from PD-L1 immunotherapy and targeted therapy.
    Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • TMB (Tumor Mutational Burden) • PAX8 (Paired box 8) • MUC5AC (Mucin 5AC) • MUC6 (Mucin 6)
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    HER-2 mutation • TMB-L • MUC5AC expression
    2ms
    CDK4 gene copy number increase and concurrent genetic changes in acral melanoma of a Chinese cohort. (PubMed, Pathology)
    CDK4 high-level copy number increase coexists with other pathogenic mutations in AM. CDK4 appears to be a promising target for AM treatment and is expected to be combined with other targeted therapies.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • BCL2L11 (BCL2 Like 11)
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    BRAF mutation • NRAS mutation • HER-2 mutation • BCL2L1 mutation • CDK4 mutation
    2ms
    Impact of select actionable genomic alterations on efficacy of neoadjuvant immunotherapy in resectable non-small cell lung cancer. (PubMed, J Immunother Cancer)
    Patients with NSCLC harboring select AGAs, including EGFR and ALK alterations, have a higher risk for TF, shorter median time to TF, and diminished pathological regression after neoadjuvant ICIs. The suboptimal efficacy of neoadjuvant chemotherapy-sparing, ICI-based regimens in this patient subset underscores the importance of tumor molecular testing prior to initiation of neoadjuvant ICI therapy in patients with resectable NSCLC.
    Clinical • Journal • PD(L)-1 Biomarker • IO biomarker
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene)
    |
    EGFR mutation • BRAF mutation • HER-2 mutation • RET fusion
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    Opdivo (nivolumab) • Yervoy (ipilimumab)
    2ms
    DESTINY-LUNG02: Trastuzumab Deruxtecan in Participants With HER2-mutated Metastatic Non-small Cell Lung Cancer (NSCLC) (clinicaltrials.gov)
    P2, N=152, Completed, Daiichi Sankyo | Active, not recruiting --> Completed
    Trial completion • Metastases
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    HER-2 (Human epidermal growth factor receptor 2)
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    HER-2 mutation
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    Enhertu (fam-trastuzumab deruxtecan-nxki)
    2ms
    Selective targeting of oncogenic hotspot mutations of the HER2 extracellular domain. (PubMed, Nat Chem Biol)
    These antibodies as T cell engagers selectively killed a HER2 S310F-driven cancer cell line in vitro, and in vivo as a xenograft. These results validate HER2 ECD mutations as actionable therapeutic targets and offer promising candidates toward clinical development.
    Journal
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    HER-2 (Human epidermal growth factor receptor 2)
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    HER-2 mutation • HER-2 S310F • HER-2 S310Y
    2ms
    Efficacy of immune checkpoint inhibitors plus platinum-based chemotherapy as 1st line treatment for patients with non-small cell lung cancer harboring HER2 mutations: Results from LC-SCRUM-Asia. (PubMed, Lung Cancer)
    Addition of ICIs to platinum-based chemotherapy in 1st line treatment may improve the PFS in patients with HER2-mutant NSCLC. The relatively high TMB might be involved in the prolongation of the PFS in patients with HER2-mutant NSCLC receiving platinum-based chemotherapy with ICIs.
    Journal • Checkpoint inhibition • Tumor mutational burden • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden)
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    EGFR mutation • TMB-H • HER-2 mutation • HER-2 exon 20 insertion • ALK fusion • HER-2 exon 20 mutation
    2ms
    Minimal Residual Disease Detection with Urine-derived DNA Is Prognostic for Recurrence-free Survival in Bacillus Calmette-Guérin-unresponsive Non-muscle-invasive Bladder Cancer Treated with Nadofaragene Firadenovec. (PubMed, Eur Urol Oncol)
    P2; Urinary MRD testing after nadofaragene firadenovec induction provided statistically significant prognostication of recurrence among phase 2 trial participants.
    Journal • Minimal residual disease
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    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • ARID1A (AT-rich interaction domain 1A) • ELF3 (E74 Like ETS Transcription Factor 3)
    |
    HER-2 mutation
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    UroAmp
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    Adstiladrin (nadofaragene firadenovec-vncg)
    2ms
    Diagnostic utility of ESR1 mutation detection in liquid biopsy of metastatic breast cancer patients. (PubMed, Virchows Arch)
    In the liquid biopsies, we detected ESR1 mutations in 42 cases (25.9%) and ERBB2 mutations in six cases (3.7%), arguing for a change in therapy to fulvestrant, elacestrant, or neratinib. Furthermore, 17 cases had detectable TP53 mutations, associated with resistance against endocrine therapy. We conclude that liquid biopsy testing is a noninvasive, sensitive, and helpful method to optimize therapeutic decisions in metastatic BC.
    Journal • Liquid biopsy • Metastases • Biopsy
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    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
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    TP53 mutation • HER-2 mutation • ER mutation • ESR1 mutation
    |
    Nerlynx (neratinib) • fulvestrant • Orserdu (elacestrant)