A5042829950- HER2/EGFR in Cancer Research
- Advanced Breast Cancer Therapies
- Social and Educational Sciences
- Lung Cancer Treatments and Mutations
- Breast Cancer Treatment Studies
- Cancer Genomics and Diagnostics
- Cancer Treatment and Pharmacology
- Epigenetics and DNA Methylation
- Medical Imaging Techniques and Applications
- Estrogen and related hormone effects
- Monoclonal and Polyclonal Antibodies Research
- Global Cancer Incidence and Screening
- Radiomics and Machine Learning in Medical Imaging
- Single-cell and spatial transcriptomics
- Cancer Risks and Factors
- Counseling, Therapy, and Family Dynamics
- Radiopharmaceutical Chemistry and Applications
- Cancer Diagnosis and Treatment
- Gene expression and cancer classification
- EFL/ESL Teaching and Learning
- Breast Lesions and Carcinomas
- RNA modifications and cancer
- Health, Environment, Cognitive Aging
- Nutrition, Genetics, and Disease
- Genomics and Chromatin Dynamics
Karolinska University Hospital
2014-2024
Breast Cancer Now
2023-2024
King's College London
2023-2024
Laerdal (Norway)
2024
Karolinska Institutet
1993-2024
Linnaeus University
2022
Karlstad University
2021
Imperial College London
2017-2019
The London College
2018
Swedish Radiation Safety Authority
1993
Abstract Purpose: Anti-EGFR antibodies show limited response in breast cancer, partly due to activation of compensatory pathways. Furthermore, despite the clinical success cyclin-dependent kinase (CDK) 4/6 inhibitors hormone receptor–positive tumors, aggressive triple-negative cancers (TNBC) are largely resistant CDK2/cyclin E expression, whereas free CDK2 display normal tissue toxicity, limiting their therapeutic application. A cetuximab-based antibody drug conjugate (ADC) carrying a CDK...
<h3>Importance</h3> Benign breast diseases (BBDs) are common and associated with cancer risk, yet the etiology risk of BBDs have not been extensively studied. <h3>Objective</h3> To investigate by age, hormonal factors, family history cancer. <h3>Design, Setting, Participants</h3> This retrospective cohort study assessed 70 877 women from population-based Karolinska Mammography Project for Risk Prediction Breast Cancer (KARMA) who attended mammographic screening or underwent clinical...
PURPOSE To assess the long-term (20-year) endocrine therapy benefit in premenopausal patients with breast cancer. METHODS Secondary analysis of Stockholm trial (STO-5, 1990-1997) randomly assigning 924 to 2 years goserelin (3.6 mg subcutaneously once every 28 days), tamoxifen (40 orally daily), combined and tamoxifen, or no adjuvant (control) is performed. Random assignment was stratified by lymph node status; node–positive (n = 459) were allocated standard chemotherapy (cyclophosphamide,...
Abstract Early cancer detection has the potential to significantly improve treatment outcomes and survival rates. Epigenetic biomarkers in cell-free DNA, including DNA methylation, have been shown differentiate between non-cancer are already being integrated into liquid biopsy development programs. Traditional methylation sequencing provides a conflated modified Cytosine (modC) readout, measuring CpGs that 5-methylcytosine (5mC) or 5-hydroxymethylcytosine (5hmC) but not discriminating two...
Abstract The metastatic potential of estrogen receptor (ER)‐positive breast cancers is heterogeneous and distant recurrences occur months to decades after primary diagnosis. We have previously shown that patients with tumors classified as ultralow risk by the 70‐gene signature a minimal long‐term fatal cancer. Here, we evaluate unexplored underlying clinical molecular characteristics in 538 ER‐positive from Stockholm tamoxifen randomized trial (STO‐3). Out 98 tumors, 89% were luminal A...
Use of immunohistochemistry-based surrogates molecular breast cancer subtypes is common in research and clinical practice, but information on their comparative validity prognostic capacity scarce.Data from 2 PAM50-subtyped Swedish cohorts were used: Stockholm tamoxifen trial-3 with 561 patients diagnosed 1976-1990 Clinseq 237 2005-2012. We evaluated 3 surrogate classifications; the immunohistochemistry-3 classifier based estrogen receptor, progesterone HER2 St. Gallen Prolif classifiers also...
<h3>Importance</h3> Clinically used breast cancer markers, such as tumor size, grade, progesterone receptor (PR) status, and Ki-67 are known to be associated with short-term survival, but the association of these markers long-term (25-year) survival is unclear. <h3>Objective</h3> To assess clinically treatment benefit among postmenopausal women lymph node–negative, estrogen [ER]–positive and<i>ERBB2</i>-negative who received tamoxifen therapy. <h3>Design, Setting, Participants</h3> This...
Abstract Background The clinical utility of gene signatures in older breast cancer patients remains unclear. We aimed to determine signature prognostic capacity this patient subgroup. Methods Research versions the genomic grade index (GGI), 70-gene, recurrence score (RS), cell cycle (CCS), PAM50 risk-of-recurrence proliferation (ROR-P), and were applied 39 datasets (N = 9583). After filtering on age ≥ 70 years, presence estrogen receptor (ER) survival data, 871 remained. Signature was tested...
The clinical impact of tumor-infiltrating lymphocytes (TILs) is less known for breast cancer patients with the estrogen receptor-positive (ER+)/human epidermal growth factor receptor-negative (HER−) subtype. Here, we explored prognostic and predictive value TILs regarding distant recurrence-free interval (DRFI) cancer-specific survival (BCSS) in 763 postmenopausal randomized to receive tamoxifen vs. no systemic treatment. were assessed whole section tumor samples stained H&E divided into low...
Abstract Liquid biopsy for profiling of cell free DNA (cfDNA) in blood holds huge promise to transform how we experience and manage cancer by early detection identification residual disease subtype. While work liquid focused on the actionable somatic variations at specific loci, past decade has seen an expansion into non-genetic features, notably methylation. 5-methylcytosine (5-mC) profiles are differential from non-cancer many more loci so provide a stronger signal. Moreover, recent...
<div>AbstractPurpose:<p>Anti-EGFR antibodies show limited response in breast cancer, partly due to activation of compensatory pathways. Furthermore, despite the clinical success cyclin-dependent kinase (CDK) 4/6 inhibitors hormone receptor–positive tumors, aggressive triple-negative cancers (TNBC) are largely resistant CDK2/cyclin E expression, whereas free CDK2 display normal tissue toxicity, limiting their therapeutic application. A cetuximab-based antibody drug conjugate (ADC)...
<p>Supplementary Video 1. Confocal Z-stack 3D video of ADC colocalization within lysosome clusters. microscopy a reconstruction image live MDA-MB-468 cell showing spatial information clusters after 24 hr treatment (please also see Figure 4B). Cell represents 10 nM Alexa-Fluor-647 labelled (magenta) for hr, and stained with dye (orange) followed by Hoechst 3342 nucleus (blue).</p>
<p>ADC growth inhibition of orthotopic TNBC xenografts <i>in vivo.</i><b>A,</b> Staining for EGFR was confirmed using FFPE blocks cell line known expression pattern (see <a href="#fig3" target="_blank">Fig. 3A</a>; EGFR-high/positive: MDA-MB-468, HCC1143, MDA-MB-231, SUM149; EGFR-low: CAL51, MCF7), compared with human normal breast glandular epithelium and tonsil. Scale bar, 100 μm. <b>B,</b> Effects ADC treatment on tumor vivo</i>....
<p>Supplementary Figure 4. Live-cell confocal microscopy of ADC internalization.</p>
<p>Stochastic conjugation of cetuximab to CDK inhibitor and ADC internalization in live breast cancer cells. <b>A,</b> Flow cytometric evaluation surface EGFR expression (TNBC: MDA-MB-468, HCC1143, HCC1806, MDA-MB-231, HCC1937, SUM149, CAL51; HER2+: SKBR3; ER+: MCF7, T47D; nontumorigenic epithelial cell model: MCF10A; immune human B lymphocytes RPMI8866, RPMI8226, monocytic line U937; primary melanocyte: melanocyte). <b>B,</b> mRNA from the Cancer Cell Line...
<p>Basal-like/TNBC is associated with upregulated EGFR and G1/S-phase cell cycle genes. <b>A,</b> Gene expression analysis of <i>EGFR</i>, <i>CCNA1</i>, <i>CCNE1</i>, <i>CDK2</i> was stratified according to IHC-defined receptor status from five published databases, <i>n</i> = 6,173 primary tumors: Guy’s (TNBC vs. HER2+ ER+, 131 32 14), Sweden Cancerome Analysis Network—Breast (SCAN-B) (<i>n</i> 165 420...
<p>Supplementary Figure 2. Single-cell RNA sequencing analyses of HER2, ER and EGFR in breast cancer.</p>
<div>AbstractPurpose:<p>Anti-EGFR antibodies show limited response in breast cancer, partly due to activation of compensatory pathways. Furthermore, despite the clinical success cyclin-dependent kinase (CDK) 4/6 inhibitors hormone receptor–positive tumors, aggressive triple-negative cancers (TNBC) are largely resistant CDK2/cyclin E expression, whereas free CDK2 display normal tissue toxicity, limiting their therapeutic application. A cetuximab-based antibody drug conjugate (ADC)...
<p>Supplementary Figure 1. Expression of G1/S-phase cell cycle genes and transcriptional regulators with basal-like/TNBCs.</p>
<p>Supplementary Figure 3. Single-cell RNA sequencing analysis of G1/S-phase cell cycle genes in breast cancer.</p>