A5085436504- HER2/EGFR in Cancer Research
- Monoclonal and Polyclonal Antibodies Research
- Breast Cancer Treatment Studies
- Cancer Immunotherapy and Biomarkers
- Advanced Breast Cancer Therapies
- Peptidase Inhibition and Analysis
- Cancer Treatment and Pharmacology
- Cancer Cells and Metastasis
- Glycosylation and Glycoproteins Research
- Cancer Diagnosis and Treatment
- Colorectal Cancer Treatments and Studies
- Growth Hormone and Insulin-like Growth Factors
- Medical Imaging Techniques and Applications
- Immunotherapy and Immune Responses
- Cancer Genomics and Diagnostics
- Cancer Research and Treatments
- Cancer-related Molecular Pathways
- Multiple Myeloma Research and Treatments
- Chronic Lymphocytic Leukemia Research
- Brain Metastases and Treatment
- Meta-analysis and systematic reviews
- Herpesvirus Infections and Treatments
- Clinical Laboratory Practices and Quality Control
- Multiple and Secondary Primary Cancers
- Single-cell and spatial transcriptomics
Mayo Clinic in Arizona
2011-2025
WinnMed
2009-2023
Mayo Clinic
2000-2023
Mayo Clinic in Florida
2006-2023
Columbia University Irving Medical Center
2023
Vaccine & Gene Therapy Institute of Florida
2023
GEICAM – Spanish Breast Cancer Group
2019
German Breast group
2019
University of California, Irvine
2019
Karolinska Institutet
2019
Purpose To develop a genomic signature that predicts benefit from trastuzumab in human epidermal growth factor receptor 2–positive breast cancer. Patients and Methods DASL technology was used to quantify mRNA samples 1,282 patients enrolled onto the Combination Chemotherapy With or Without Trastuzumab Treating Women Breast Cancer (North Central Treatment Group N9831 [NCCTG-N9831]) adjuvant trial. Cox proportional hazard ratios (HRs), adjusted for significant clinicopathologic risk factors,...
Palbociclib is a cyclin-dependent kinase 4 and 6 inhibitor approved for advanced breast cancer. In the adjuvant setting, potential value of adding palbociclib to endocrine therapy hormone receptor-positive cancer has not been confirmed.
We examined associations between tumor characteristics (human epidermal growth factor receptor 2 [HER2] protein expression, HER2 gene and chromosome 17 copy number, hormone status) disease-free survival (DFS) of patients in the N9831 adjuvant trastuzumab trial.All (N = 1,888) underwent chemotherapy with doxorubicin cyclophosphamide, followed by weekly paclitaxel or without concurrent trastuzumab. status was determined immunohistochemistry (IHC) fluorescent situ hybridization (FISH) at a...
Purpose In 1998, the US Food and Drug Administration (FDA) approved human epidermal growth factor receptor 2 (HER2) testing guidelines to determine eligibility for HER2-directed therapy (HDT) in breast cancer. ASCO College of American Pathologists published immunohistochemistry (IHC) fluorescent situ hybridization (FISH) HER2 2007 (AC2007) updated these 2013 (AC2013). We compared FISH amplification frequency using three guidelines. Methods Patient samples that were sent Mayo Clinic...
Abstract The utility of spatial immunobiomarker quantitation in prognostication and therapeutic prediction is actively being investigated triple-negative breast cancer (TNBC). Here, with high-plex quantitative digital profiling, we map quantitate intraepithelial adjacent stromal tumor immune protein microenvironments systemic treatment-naïve (female only) TNBC to assess the context immunobiomarker-based outcome. Immune profiles CD45-rich CD68-rich differ significantly. While they typically...
The 2007 American Society of Clinical Oncology and College Pathologists (ASCO/CAP) joint guidelines defined criteria for HER2 positivity tumors that modified those the US Food Drug Administration (FDA), causing some confusion uncertainty among clinicians. Using data from HER2-positive breast cancer adjuvant trial N9831, we compared eligibility patients who met both criteria, disease-free survival (DFS) was assessed by Cox proportional hazards regression. number in N9831 retrospectively...
The addition of trastuzumab to chemotherapy extends survival among patients with HER2(+) breast cancer. Prior work showed that and augments HER2 extracellular domain (ECD)-specific antibodies. current study investigated whether combination therapy induced immune responses beyond HER2-ECD and, importantly, those were associated survival. Pretreatment posttreatment sera obtained from 48 women metastatic cancer on NCCTG (now Alliance for Clinical Trials in Oncology) studies, N0337 N983252. IgG...
Abstract Purpose: To investigate the associations between baseline and posttreatment circulating tumor cell (CTC) gene expression outcome of patients enrolled in four North Central Cancer Treatment Group metastatic breast cancer (MBC) trials which specimens were shipped (at 4°C) from community-based sites to a reference laboratory (Mayo Clinic, Rochester, MN). Experimental Design: Blood was collected at treating MBC before (baseline), during, end treatment with erlotinib + gemcitabine...
BACKGROUND Increased soluble human epidermal growth factor receptor 2 (sHER2) is an indicator of a poor prognosis in HER2‐positive metastatic breast cancer. In this study, the authors evaluated levels sHER2 during treatment and at time disease recurrence adjuvant North Central Cancer Treatment Group N9831 clinical trial. METHODS The objectives were to describe patients who randomized arms A (standard chemotherapy), B chemotherapy with sequential trastuzumab), C concurrent trastuzumab)....
Patients with HER2+ breast cancer treated trastuzumab and chemotherapy have superior survival compared patients alone. Polymorphisms within FCGR2A FCGR3A are associated binding affinity of natural killer cells to the IgG1 portion trastuzumab, a polymorphism in FCGR2B (I232T) is impaired regulatory activity. The association these polymorphisms clinical response among trastuzumab-treated equivocal, both positive negative associations. We performed genotyping analysis on V158F, R131H, I232T...
Activation of the RAS/MAPK pathway is associated with reduced tumor-infiltrating lymphocytes and poor outcomes in triple-negative breast cancer (TNBC). Previous studies demonstrated that inhibition MAPK a MEK inhibitor synergistic immune checkpoint inhibitors. We conducted phase I/II trial pembrolizumab binimetinib patients metastatic TNBC ≤ 3 prior lines therapy. There were two dose levels (DL) at 45 mg DL 0 30 -1. The recommended II was standard twice daily. objective response rate (ORR)...
Background: Genomic data from human epidermal growth factor receptor 2–positive (HER2+) tumors were analyzed to assess the association between intrinsic subtype and clinical outcome in a large, well-annotated patient cohort. Methods: Samples NCCTG (Alliance) N9831 trial using Prosigna algorithm on NanoString platform define subtype, risk of recurrence scores, categories for 1392 HER2+ tumors. Subtypes evaluated recurrence-free survival (RFS) Kaplan-Meier Cox model analysis following adjuvant...
Epidermal growth factor receptor (EGFR) has been hypothesised to modulate the effectiveness of anti-HER2 therapy. We used a standardised, quantitative immunofluorescence assay and novel EGFR antibody evaluate correlation between expression clinical outcome in North Central Cancer Treatment Group (NCCTG) N9831 trial.Tissue microarrays were constructed that allowed analysis 1365 patients randomly assigned receive chemotherapy alone (Arm A), sequential trastuzumab after B) with concurrent C)....
This study investigated the association between tumor MYC protein expression and disease-free survival (DFS) of patients randomized to receive chemotherapy alone (Arm A) or with sequential B) concurrent trastuzumab C) in N9831 (Alliance) adjuvant HER2(+) breast cancer trial.This analysis included 1,736 Arms A, B, C on N9831. Nuclear was determined tissue microarray sections containing three biopsies per patient whole using standard immunohistochemistry (clone 9E10). A considered positive for...
Resected HER2 breast cancer patients treated with adjuvant trastuzumab and chemotherapy have superior survival compared to alone. We previously showed that induce HER2-specific antibodies which correlate improved in metastatic patients. It remains unclear whether the generation of immunity required endogenous antibody is associated disease-free setting. In this study, we addressed question by analyzing serum anti-HER2 from a subset enrolled NCCTG trial N9831, includes an arm (Arm A) was not...
509 Background: Some 20-25% of patients with HER2+ disease relapse after adjuvant trastuzumab (H). We used a genomic approach to define biological processes that predict benefit from H. Methods: Whole genome DASL technology was identify genes associated relapse-free survival (RFS) among 1,282 enrolled in the N9831 H trial (NCT00005970). Cox proportional hazard ratios (HR), adjusted for significant clinical/pathological risk factors, were determine association each gene RFS (median follow-up...
520 Background: Targeted therapy using trastuzumab (an anti-HER-2 receptor monoclonal antibody) has significantly improved survival in breast carcinoma patients (pts), but determining which pts will respond to this remains a challenge. We previously reported (Miller DV, ASCO 2004 abstract #568) subset of with cancers demonstrating focal HER-2 amplified clones (FHAC) amidst otherwise nonamplified tumor cells by fluorescence in-situ hybridization. These accounted for 21% the...
Trastuzumab acts in part through the adaptive immune system. Previous studies showed that enrichment of immune-related gene expression was associated with improved outcomes HER2-positive (HER2+) breast cancer. However, role system response to lapatinib is not fully understood. Gene analysis performed 1,268 samples from North Central Cancer Treatment Group (NCCTG) N9831 and 244 NeoALTTO trial. In N9831, CD45 immune-subset signatures were significantly outcomes. We identified a novel 17-gene...
577 Background: BAY 43–9006 targets the ras/raf signaling pathway and inhibits VEGFR-2, VEGFR-3 or PDGFR-β growth factors. A study was conducted to assess anti-tumor activity toxicity profile in patients (pts) with metastatic breast cancer (MBC). Methods: two-stage phase II pts MBC who had measurable disease were candidates for 1 st 2 nd line chemotherapy previously received an anthracycline and/or a taxane neoadjuvant, adjuvant, setting. Pts started dose of 400 mg twice daily on days 1–28...
632 Background: Crosstalk between the insulin-like growth factor (IGF) and HER2 pathways in multiple preclinical models suggest a mechanism of resistance to HER2-targeted therapy. Cixutumumab (CIX, IMC-A12), an anti-IGF-1 Receptor monoclonal antibody, was investigated combination with capecitabine lapatinib (cape/lap) determine if addition IGF target agent would improve PFS compared cape/lap unselected HER2+ metastatic breast cancer (mbc) patients (pts). binding protein (IGFBP) levels may be...
Background: Preclinical evidence indicates that increased insulin-like growth factor receptor-1 (IGF1R) signaling interferes with the action of trastuzumab suggesting a possible mechanism resistance. Thus, we evaluated IGF1R prevalence, relationship demographic data, and association disease-free survival (DFS) patients randomized to chemotherapy alone (Arm A) or sequential B) concurrent C) in prospective phase III HER2+ adjuvant N9831 trial.Experimental Design: protein expression was...
523 Background: ASCO/CAP guidelines for HER2 testing in breast cancer were published 2007 and updated 2013. HER2-directed therapies (HDT) should be recommended patients who are deemed positive, while they not negative patients. If is equivocal, the guideline suggests that HDT considered. It known how implementation of will change clinical practice. Methods: After 2013 guidelines, 321 tumor samples received by Mayo Clinic Cytogenetics laboratory FISH analysis status. The prevalence...