A5064957782- Cancer Genomics and Diagnostics
- Estrogen and related hormone effects
- Advanced Breast Cancer Therapies
- Genetic factors in colorectal cancer
- BRCA gene mutations in cancer
- Cancer Cells and Metastasis
- Lung Cancer Treatments and Mutations
- Single-cell and spatial transcriptomics
- Lung Cancer Research Studies
- Molecular Biology Techniques and Applications
- Chronic Lymphocytic Leukemia Research
- Cancer Immunotherapy and Biomarkers
- Breast Cancer Treatment Studies
- HER2/EGFR in Cancer Research
- Ferroptosis and cancer prognosis
- Genetics, Bioinformatics, and Biomedical Research
- Cancer-related molecular mechanisms research
- CRISPR and Genetic Engineering
- Colorectal Cancer Treatments and Studies
- Viral-associated cancers and disorders
- RNA modifications and cancer
- DNA Repair Mechanisms
- Cancer-related Molecular Pathways
Breast Cancer Now
2016-2024
Institute of Cancer Research
2016-2022
Royal Bournemouth Hospital
2019
Royal Marsden Hospital
2016-2019
Royal Cornwall Hospital Trust
2019
Poole Hospital
2019
Hinchingbrooke Hospital
2019
Roche (United Kingdom)
2017
Roche (Switzerland)
2017
Randox (United Kingdom)
2012
ESR1 mutations are selected by prior aromatase inhibitor (AI) therapy in advanced breast cancer. We assessed the impact of on sensitivity to standard therapies two phase III randomized trials that represent development current for estrogen receptor-positive cancer.In a prospective-retrospective analysis, we available archived baseline plasma from SoFEA (Study Faslodex Versus Exemestane With or Without Arimidex) trial, which compared exemestane with fulvestrant-containing regimens patients...
Abstract CDK4/6 inhibition substantially improves progression-free survival (PFS) for women with advanced estrogen receptor-positive breast cancer, although there are no predictive biomarkers. Early changes in circulating tumor DNA (ctDNA) level may provide early response prediction, but the impact of heterogeneity is unknown. Here we use plasma samples from patients randomized phase III PALOMA-3 study inhibitor palbociclib and fulvestrant cancer show that relative change PIK3CA ctDNA after...
<h3>Importance</h3> Current treatment cures most cases of early-stage, primary breast cancer. However, better techniques are required to identify which patients at risk relapse. <h3>Objective</h3> To assess the clinical validity molecular relapse detection with circulating tumor DNA (ctDNA) analysis in early-stage <h3>Design, Setting, and Participants</h3> This prospective, multicenter, sample collection, validation study conducted 5 United Kingdom medical centers from November 24, 2011,...
Abstract Purpose: Triple-negative breast cancer (TNBC) is a heterogeneous subgroup of that associated with poor prognosis. We evaluated the activity CDK4/6 inhibitors across TNBC subtypes and investigated mechanisms sensitivity. Experimental Design: A panel cell lines representative was tested for in vitro vivo sensitivity to inhibition. fluorescent CDK2 reporter used single-cell analysis conjunction time-lapse imaging. Results: The luminal androgen receptor (LAR) subtype highly sensitive...
Post-treatment detection of circulating tumour DNA (ctDNA) in early-stage triple-negative breast cancer (TNBC) patients predicts high risk relapse. c-TRAK TN assessed the utility prospective ctDNA surveillance TNBC and activity pembrolizumab with detected [ctDNA positive (ctDNA+)].c-TRAK TN, a multicentre phase II trial, integrated by digital PCR, enrolled residual disease following neoadjuvant chemotherapy, or stage II/III adjuvant chemotherapy. comprised three-monthly blood sampling to 12...
Abstract Purpose: ESR1 mutations are acquired frequently in hormone receptor–positive metastatic breast cancer after prior aromatase inhibitors. We assessed the clinical utility of baseline circulating tumor DNA (ctDNA) analysis two phase III randomized trials fulvestrant versus exemestane. Experimental Design: The EFECT and SoFEA patients with who had progressed on nonsteroidal inhibitor therapy, between 250 mg Baseline serum samples from 227 EFECT, plasma 161 SoFEA, were analyzed for by...
Circulating tumor DNA (ctDNA) assays are increasingly used for clinical decision-making, but it is unknown how well different agree. We aimed to assess the agreement in ctDNA mutation calling between BEAMing (beads, emulsion, amplification, and magnetics) droplet digital PCR (ddPCR), 2 of most commonly techniques detecting mutations ctDNA.Baseline plasma samples from patients with advanced breast cancer enrolled phase 3 PALOMA-3 trial were assessed ESR1 PIK3CA both ddPCR. Concordance...
Abstract The genomics of advanced breast cancer (ABC) has been described through tumour tissue biopsy sequencing, although these approaches are limited by geographical and temporal heterogeneity. Here we use plasma circulating DNA sequencing to interrogate the genomic profile ABC in 800 patients plasmaMATCH trial. We demonstrate diverse subclonal resistance mutations, including enrichment HER2 mutations positive disease, co-occurring ESR1 MAP kinase pathway HR + HER2− disease that associate...
Circulating tumor DNA (ctDNA) analysis has the potential to allow non-invasive of mutations in advanced cancer. In this study we assessed reproducibility digital PCR (dPCR) assays circulating a cohort patients with breast cancer and delayed plasma processing using cell free preservative tubes. We recruited 96 paired samples from 71 women who had blood processed either immediately or tubes 48–72 hours after collection. Plasma was analysed multiplex (mdPCR) for hotspot PIK3CA, ESR1 ERBB2, AKT1...
Abstract PIK3CA is one of the two most frequently mutated genes in breast cancers, occurring 30–40% cases. Four frequent ‘hotspot’ mutations (E542K, E545K, H1047R and H1047L) account for 80–90% all human malignancies represent predictive biomarkers. Here we describe a mutation specific nuclease-based enrichment assay, which combined with low-cost real-time qPCR detection method, enhances assay sensitivity from 5% E542K 10% E545K to 0.6%, 0.3%. Moreover, present novel flexible prediction...
Abstract Background Detection of circulating tumour DNA (ctDNA) in patients (pts) who have completed treatment for early-stage triple negative breast cancer (TNBC) is associated with a very high risk future relapse. Identifiying those at subsequent relapse may allow tailoring further therapy to delay or prevent recurrence. The c-TRAK TN trial assessed the utility prospective ctDNA surveillance pts treated TNBC and activity pembrolizumab (P) detected.. Methods TN, multi-centre phase II...
1001 Background: CDK4/6 inhibition combined with endocrine therapy is now a standard of care for advanced estrogen receptor (ER) positive breast cancer. Mechanisms resistance to inhibitors have been described in pre-clinical models, although there limited evidence from clinical samples. We investigated the mechanisms inhibitor PALOMA3 trial using ctDNA analysis. Methods: The phase III randomized 521 patients pre-treated disease palbociclib and fulvestrant (P+F) versus placebo (F). Using...
Abstract Background: Circulating tumor DNA (ctDNA) is found in the plasma of over 90% patients with advanced breast cancer (BC). ctDNA analysis can establish current genomic profile an individual’s and identify potentially targetable mutations. The landscape BC clinical associations has yet to be fully defined. This describes screened for UK plasmaMATCH study. Methods: trial was open-label, multi-centre, multi-cohort platform trial, consisting testing ~1000 BC. consists parallel treatment...
1018 Background: Palbociclib improves progression free survival (PFS) in patients with advanced, hormone receptor positive, HER2-negative breast cancer. There are currently no biomarkers to predict sensitivity palbociclib. We investigated if early circulating tumour DNA (ctDNA) dynamics could clinical outcome on palbociclib (Palbo) and fulvestrant (F) the PALOMA-3 trial. Methods: Plasma samples were prospectively collected for ctDNA analysis at baseline, cycle 1 day 15 (D15) end of treatment...
Abstract Introduction: Identification of Molecular Residual Disease (MRD) by circulating tumour DNA (ctDNA) analysis has the potential to transform clinical management patients with early breast cancer. We present results from a proof-of-principle study assess ctDNA following primary surgery identify MRD and anticipate which are at risk relapse. Methods: Early cancer receiving for (48 total), enrolled in PlasmaDNA/ITH sample collection studies were included analysis. Tumour FFPE samples was...
Abstract Background. ESR1 mutations are selected by prior aromatase inhibitor (AI) therapy for advanced breast cancer. We addressed the impact of on sensitivity to standard therapies in SoFEA and PALOMA3, two phase III randomised trials that represent trends current estrogen receptor positive Methods. assessed plasma DNA trial compared exemestane with fulvestrant-containing regimens patients non-steroidal AI, PALOMA3 fulvestrant plus placebo palbociclib progression endocrine therapy....
Abstract Background In a previous proof-of-principle study we demonstrated that detection of circulating tumour DNA (ctDNA) in the adjuvant setting, after completion surgery and chemotherapy for early stage breast cancer, was associated with high risk relapse. Here present longer follow-up same series, to define predictive power ctDNA analysis disease free survival, assess potential predict overall survival. Methods We recruited cohort 55 women presenting stage, primary who were all...
1015 Background: Selection of resistance mutations may play a major role in the development endocrine resistance. ESR1 are rare primary breast cancer but have high prevalence patients treated with aromatase inhibitors (AI) for advanced cancer. We investigated evolution genetic to first line AI therapy using sequential ctDNA sampling Methods: Seventy-one on metastatic were enrolled prospective study collect plasma samples analysis every three months therapy, and at disease progression. All...
<p>Supplementary Figure 2. Consort diagram of patients analysed from EFECT</p>
<p>Supplementary Figure 6. Progression free survival in monoclonal and polyclonal ESR1 mutations</p>