Publications by authors named "Wardley A"

Article Synopsis
  • * In the cTRAK-TN trial with 141 patients, personalized multimutation sequencing (47.9%) was more effective at first detecting minimal residual disease (MRD) than digital PCR, which showed 0% detection at the same time.
  • * Patients whose MRD was detected earlier had shorter lead times to relapse, highlighting the clinical significance of using personalized sequencing for early detection and potential better outcomes.
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Background: Adjuvant chemotherapy for patients with early breast cancer improves outcomes but its toxicity affects patients' quality of life (QOL). The UK TACT2 trial investigated whether accelerated epirubicin improves time to recurrence and if oral capecitabine is non-inferior to cyclophosphamide, methotrexate, and fluorouracil (CMF) for efficacy with less toxicity. Results showed no benefit for accelerated epirubicin and capecitabine was non-inferior.

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  • The ABRAZO trial studied how mutations in homologous recombination repair genes, specifically BRCA1/2, affect the effectiveness of the PARP inhibitor talazoparib in patients with those mutations.
  • Out of 60 patients evaluated, a significant majority (97%) had BRCA1/2 mutations, with a high rate of concordance (95%) between germline and tumor mutations, and many exhibited homologous recombination deficiency (HRD).
  • Non-BRCA mutations, such as TP53 and PIK3CA, are common in this population, but they do not seem to impact the sensitivity to talazoparib, which indicates the primary importance of BRCA mutations for treatment efficacy.
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Purpose: Approximately 10% to 15% of triple-negative breast cancers (TNBC) have deleterious mutations in BRCA1 and BRCA2 and may benefit from PARP inhibitor treatment. PARP inhibitors may also increase exogenous replication stress and thereby increase sensitivity to inhibitors of ataxia telangiectasia and Rad3-related (ATR) protein. This phase II study examined the activity of the combination of PARP inhibitor, olaparib, and ATR inhibitor, ceralasertib (AZD6738), in patients with advanced TNBC.

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Introduction: Adolescence is a period of major transition in physical, cognitive, social and emotional development, and the peak time for the onset of mental health conditions, substance use disorders and sexual and reproductive health risks. Prevention and treatment during this time can improve health and well-being now and into the future. However, despite clinical guidelines recommending annual preventive health assessments for young people, health professionals cite lack of consultation time and adequate funding as key barriers.

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Background And Objectives: There have been calls for a Medicare Benefits Schedule rebate to support a young person's health assessment in general practice. The aim of this study was to understand Victorian providers' needs and perspectives about implementing young people's health assessments in general practice.

Method: Focus groups and interviews were conducted over Zoom with current general practitioners (GPs), practice nurses (PNs) and practice managers (PMs).

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Background: Men who have sex with men (MSM) taking pre-exposure prophylaxis (PrEP) are recommended to have screening for asymptomatic chlamydia and gonorrhoea every 3months with high rates of asymptomatic chlamydia and gonorrhoea detected. However, there is little evidence about the effectiveness of this screening interval and there is increasing concern about antibiotic consumption and its impact on antimicrobial resistance. There have been calls to reconsider this frequent screening for chlamydia and gonorrhoea.

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Introduction: Anthracyclines are included in chemotherapy regimens to treat several different types of cancer and are extremely effective. However, it is recognised that a significant side effect is cardiotoxicity; anthracyclines can cause irreversible damage to cardiac cells and ultimately impaired cardiac function and heart failure, which may only be evident years after exposure. The PROACT trial will establish the effectiveness of the ACE inhibitor enalapril maleate (enalapril) in preventing cardiotoxicity in patients with breast cancer and non-Hodgkin's lymphoma (NHL) receiving anthracycline-based chemotherapy.

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Article Synopsis
  • The c-TRAK TN trial investigated the use of circulating tumor DNA (ctDNA) surveillance as a method to predict relapse in early-stage triple-negative breast cancer (TNBC) patients after treatment.
  • The trial enrolled patients with residual disease post-chemotherapy and involved blood tests every three months for a year to monitor ctDNA levels, with ctDNA+ patients receiving pembrolizumab if indications of recurrence were found.
  • Out of 161 patients monitored, 27.3% tested positive for ctDNA within 12 months, but only five were treated with pembrolizumab, and none showed a complete response, highlighting challenges in effectively using ctDNA monitoring for treatment decisions.
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Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose limiting toxicity posing a major clinical challenge for managing patients receiving specific chemotherapy regimens (e.g., Taxanes).

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Background: The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting.

Patients And Methods: Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity.

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Background: In the phase III IMpassion130 trial, combining atezolizumab with first-line nanoparticle albumin-bound-paclitaxel for advanced triple-negative breast cancer (aTNBC) showed a statistically significant progression-free survival (PFS) benefit in the intention-to-treat (ITT) and programmed death-ligand 1 (PD-L1)-positive populations, and a clinically meaningful overall survival (OS) effect in PD-L1-positive aTNBC. The phase III KEYNOTE-355 trial adding pembrolizumab to chemotherapy for aTNBC showed similar PFS effects. IMpassion131 evaluated first-line atezolizumab-paclitaxel in aTNBC.

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Aims: In HER2CLIMB, tucatinib significantly improved progression-free and overall survival in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer. We evaluated the impact of tucatinib on health-related quality of life (HR-QoL) in HER2CLIMB.

Methods: Patients were randomised 2:1 to tucatinib or placebo combined with trastuzumab and capecitabine.

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Treatment of HER2-positive early breast cancer (EBC) continues to evolve with neoadjuvant (pre-operative) and adjuvant (post-operative) HER2-targeted therapies as standard of care. There are two important decision points. The first involves deciding between neoadjuvant therapy or proceeding directly to surgery.

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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 tumour DNA sequencing to interrogate the genomic profile of ABC in 800 patients in the plasmaMATCH trial. We demonstrate diverse subclonal resistance mutations, including enrichment of HER2 mutations in HER2 positive disease, co-occurring ESR1 and MAP kinase pathway mutations in HR + HER2- disease that associate with poor overall survival (p = 0.

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Purpose: Androgen receptor (AR) expression occurs in up to 86% of human epidermal growth factor receptor 2-positive (HER2+) breast cancers. In vitro, AR inhibitors enhance antitumor activity of trastuzumab, an anti-HER2 antibody, in trastuzumab-resistant HER2+ cell lines. This open-label, single-arm, phase II study evaluated the efficacy and safety of enzalutamide, an AR-signaling inhibitor, in patients with advanced HER2+ AR+ breast cancer previously treated with trastuzumab.

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Treatment of patients with cancer in hospitals or clinics is resource-intensive and imposes a burden on patients. 'Flexible care' is a term that can be used to describe treatment administered outside the oncology ward, oncological outpatient clinic or office-based oncologist setting. Programmes that reduce travel burden by bringing cancer treatment to the patient's home, workplace or closer to the patient's home, in the form of satellite clinics or mobile cancer units, expand treatment capacity and are well received.

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Background: Endocrine therapy resistance is a major cause of distant recurrence (DR) in hormone receptor-positive breast cancer. This study evaluated differences in survival after DR in patients treated with different adjuvant endocrine therapy regimens in the Breast International Group (BIG) 1-98 trial.

Methods: BIG 1-98 compared 5 years of adjuvant treatment among 4 arms: tamoxifen (T), letrozole (L), tamoxifen followed by letrozole (TL), and letrozole followed by tamoxifen (LT).

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Enormous advances have been made in the understanding and treatment of human epidermal growth factor receptor 2-positive breast cancer (HER2+ BC) in the last 30 years that have resulted in survival gains for affected patients. A growing body of evidence suggests that hormone receptor-positive (HR+)/HER2+ BC and HR-negative (HR-)/HER2+ BC are biologically different, with complex molecular bidirectional crosstalk between the estrogen receptor and HER2 pathway potentially affecting sensitivity to both HER2-targeted and endocrine therapy in patients with HR+/HER2+ BC. Subgroup analyses from trials enrolling patients with HER2+ BC and the results of clinical trials specifically designed to evaluate therapy in patients with HR+/HER2+ BC are helping to guide treatment decisions.

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Background: Compared to tamoxifen, adjuvant treatment with aromatase inhibitors improves disease outcomes of postmenopausal women with hormone receptor-positive early breast cancer. In the international, randomized, double-blind BIG 1-98 trial, 8010 women were randomized to receive tamoxifen, letrozole, or sequential use of the agents for 5 years. With a focus on switching between agents, we investigated cardiovascular events over the entire 5-year treatment period.

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Background: The impact of different disease stages and treatment for human epidermal growth factor 2 positive (HER2-positive) breast cancer (BC) on work productivity and health-related quality of life (HRQoL) is poorly understood.

Methods: This was a UK cross-sectional study of 299 adult patients with HER2-positive early or metastatic BC (NCT03099200). Productivity was assessed using the work productivity and activity impairment scale; HRQoL was measured using EuroQol-5 Dimensions-5 levels (EQ-5D-5L), and Functional Assessment of Cancer Therapy Breast (FACT-G and -B) instruments.

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Purpose: Many patients with HR+, HER2- early breast cancer (EBC) will not experience recurrence or have distant recurrence with currently available standard therapies. However, up to 30% of patients with high-risk clinical and/or pathologic features may experience distant recurrence, many in the first few years. Superior treatment options are needed to prevent early recurrence and development of metastases for this group of patients.

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Article Synopsis
  • The study investigates the effectiveness of ctDNA testing in advanced breast cancer, aimed at avoiding repeat biopsies and helping to select patients for targeted therapies based on their genetic mutations.
  • Conducted across 18 UK hospitals, it involved women with advanced breast cancer who had undergone prior treatments, and assessed responses to various mutation-specific treatments aligned with their ctDNA profiles.
  • The trial is ongoing, with recruitment completed and primary endpoints focused on measuring response rates, and is registered under several clinical trial databases.
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Article Synopsis
  • The study aimed to compare the effectiveness of 6 months versus 12 months of adjuvant trastuzumab in treating HER2-positive early breast cancer, with the main goal of determining if the shorter duration was as effective in preventing disease recurrence after 4 years.
  • Conducted as a Phase III randomized controlled trial across 152 NHS hospitals, it involved 4,088 patients who were randomly assigned to receive either 6 or 12 months of trastuzumab treatment alongside chemotherapy.
  • The primary outcome measured was disease-free survival, while secondary outcomes included overall survival, cost-effectiveness, and cardiac function, with an emphasis on showing that the shorter treatment duration remains within a non-inferiority
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