Publications by authors named "Okines A"

Human epidermal growth factor receptor 2 (HER2) overexpression and/or ERBB2 gene amplification occurs in approximately 15-20% of breast cancers and is associated with poor prognosis. While the introduction of HER2-targeted therapies has significantly improved survival in patients with HER2-positive metastatic breast cancer, the incidence of brain metastases has increased due to patients living longer. Current recommendations sequence treatments by line of therapy, as well as by the status of brain metastases in patients with HER2-positive breast cancer.

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Background: In early breast cancer (EBC) patients, we aimed to determine whether circulating tumor DNA (ctDNA) analysis following primary surgery, before systemic therapy, identified molecular residual disease and was associated with risk of relapse and relapse-free survival (RFS).

Methods: Plasma was collected, retrospectively, before surgery, 1-14 weeks post-operatively, and before adjuvant therapy, and in a subset of patients after adjuvant therapy. A personalized, tumor-informed, multiplex PCR next generation sequencing assay (Signatera™) was used for ctDNA detection and quantification.

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Pseudocirrhosis is a diffuse nodularity of the liver that radiologically mimics cirrhosis but is a distinct pathological process. It is seen almost exclusively in patients with liver metastases and may represent a response to systemic treatment. Data on the risk factors for pseudocirrhosis and outcomes are limited.

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Article Synopsis
  • The PI3K/AKT/mTOR signaling pathway is crucial in breast cancer and other bodily functions, with ongoing research focused on developing inhibitors for this pathway in advanced breast cancer treatment.
  • Currently, only three inhibitors—everolimus, alpelisib, and capivasertib—are approved for use against this pathway in ER-positive, HER2-negative breast cancer, but drug resistance remains a significant challenge.
  • Resistance can be intrinsic (existing before treatment) or acquired (developing during treatment), affecting most patients and highlighting the need for more research on resistance mechanisms and management strategies, particularly concerning AKT1 inhibitors.*
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Purpose: Many patients with early breast cancer (eBC) undergoing neoadjuvant chemotherapy do not achieve pathological complete response (pCR), which is a prognostic factor. We examined the role of HER2-low expression in predicting pCR and prognosis in HER2-negative eBC.

Methods: We evaluated patients with stage I-III HER2-negative BC, treated between 2013 and 2023 at The Royal Marsden NHS Foundation Trust, London.

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Background: Treatment options for pre-treated patients with metastatic triple-negative breast cancer (mTNBC) remain limited. This is the first study to assess the real-world safety and efficacy of sacituzumab govitecan (SG) in the UK.

Methods: Data was retrospectively collected from 16 tertiary UK cancer centres.

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Despite recent advances, HER2-positive advanced breast cancer (ABC) remains a largely incurable disease, with resistance to conventional anti-HER2 drugs ultimately unavoidable for all but a small minority of patients who achieve an enduring remission and possibly cure. Over the past two decades, significant advances in our understanding of the underlying molecular mechanisms of HER2-driven oncogenesis have translated into pharmaceutical advances, with the developing of increasingly sophisticated therapies directed against HER2. These include novel, more potent selective HER2 tyrosine kinase inhibitors (TKIs); new anti-HER2 antibody-drug conjugates; and dual epitope targeting antibodies, with more advanced pharmacological properties and higher affinity.

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  • * 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: There is currently no standardised definition for patients at high risk of recurrence of human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (eBC; stages 1-3) after surgery. This modified Delphi panel aimed to establish expert UK consensus on this definition, separately considering hormone receptor (HR)-positive and triple-negative (TN) patients.

Methods: Over three consecutive rounds, results were collected from 29, 24 and 22 UK senior breast cancer oncologists and surgeons, respectively.

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Purpose: To evaluate the efficacy and safety of tucatinib and trastuzumab in patients with previously treated human epidermal growth factor receptor 2-positive (HER2+) metastatic biliary tract cancer (mBTC).

Methods: SGNTUC-019 (ClinicalTrials.gov identifier: NCT04579380) is an open-label phase II basket study evaluating the efficacy and safety of tucatinib and trastuzumab in patients with HER2-altered solid tumors.

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Until recently, despite its heterogenous biology, metastatic triple negative breast cancer (TNBC) was treated as a single entity, with successive lines of palliative chemotherapy being the only systemic option. Significant gene expression studies have demonstrated the diversity of TNBC, but effective differential targeting of the four main (Basal-like 1 and 2, mesenchymal and luminal androgen receptor) molecular sub-types has largely eluded researchers. The introduction of immunotherapy, currently useful only for patients with PD-L1 positive cancers, led to the stratification of first-line therapy using this immunohistochemical biomarker.

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Background: The full range of cardiovascular complications related to the use of Immune checkpoint inhibitors (ICI) is not fully understood. We aim to describe the spectrum of cardiovascular adverse events (cvAEs) by presenting our real-world experience of the diagnosis and management of these complications.

Methods: Two thousand six hundred and forty-seven (2647) patients were started on ICI treatment between 2014 and 2020.

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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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Advances in treatment, common cardiovascular (CV) risk factors and the ageing of the population have led to an increasing number of cancer patients presenting with acute CV diseases. These events may be related to cancer itself or cancer treatment. Acute cardiac care specialists must be aware of these acute CV complications and be able to manage them.

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Purpose: To describe the tolerability and efficacy of neratinib as a monotherapy and in combination with capecitabine in advanced HER2-positive breast cancer in a real-world setting.

Methods: Patients who received neratinib for advanced HER2-positive at the Royal Marsden Hospital NHS Trust between August 2016 and May 2020 were identified from electronic patient records and baseline characteristics, previous treatment and response to treatment were recorded. The primary endpoint of the study was progression-free survival (PFS).

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Introduction: The tubulin inhibitor, eribulin, improves survival for previously treated advanced breast cancer (ABC) compared to chemotherapy of physician's choice, including vinorelbine, an older anti-tubulin. Vinorelbine is commonly still used after eribulin, but potentially risks cross-resistance and its efficacy in this setting is unproven.

Materials And Methods: A retrospective analysis of all patients who received vinorelbine after prior eribulin (VAE) 2011-2015 and a parallel cohort of consecutive patients who received vinorelbine without prior eribulin (VWE) for previously treated ABC between 2005 and 2011.

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Background: The assessment of metastatic breast cancer (MBC) can be limited with routine imaging such as computed tomography (CT) especially in bone-only or bone-predominant disease. This analysis investigates the effects of the use of WBMRI in addition to the use of routine CT, bone scintigraphy (BS) and fluorine-18-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) on influencing systemic anti-cancer treatment (SACT) decisions in patients with known MBC.

Methods: MBC patients undergoing SACT who had WBMRI undertaken within 8 weeks of either a routine CT, BS or FDG-PET/CT were reviewed retrospectively.

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Article Synopsis
  • Invasive lobular breast carcinomas (ILC) make up around 15% of breast cancer cases and are harder to diagnose due to their unique growth and spread patterns, which include metastasis to unusual sites like peritoneum and GI tract.
  • Traditional imaging methods like CT might struggle with assessing ILC, especially when bone involvement is predominant, while whole-body MRI (WBMRI) can provide better evaluation of both bone and soft tissue disease due to its functional imaging capabilities.
  • Recent studies indicate that WBMRI can identify more metastatic sites in breast cancer, leading to changes in treatment plans, and can be especially important for non-FDG-avid ILC cases that traditional FDG-PET/CT might underestimate.
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  • * Out of those tested, 118 had COVID-19, with 94 showing symptoms and only 2 fatalities, revealing high levels of S1-reactive and neutralizing antibodies against the virus.
  • * Immune responses varied, particularly with hematological cancer patients showing unique challenges but still managing clinical recovery, highlighting the need for more research on immune durability against different SARS-CoV-2 variants.
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  • The CAPTURE study evaluated COVID-19 immunity in 585 cancer patients after receiving two doses of either BNT162b2 or AZD1222 vaccines, revealing seroconversion rates of 85% for those with solid tumors and 59% for those with hematological malignancies.
  • Patients with hematological cancers had significantly lower levels of detectable neutralizing antibodies (NAbT) against SARS-CoV-2 variants compared to those with solid tumors and healthy individuals.
  • Previous COVID-19 infections increased NAb responses, particularly against variants, but treatment with anti-CD20 medications correlated with undetectable NAbT, highlighting important considerations for cancer patient management during the pandemic.
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Purpose: Invasive lobular carcinomas (ILC) are characterised by loss of the cell adhesion molecule E-cadherin. Approximately 15% of ILC are ER negative at the time of breast cancer diagnosis, or at relapse due to loss of ER expression. Less than 5% of classical ILC but up to 35% of pleomorphic ILC are HER2 positive (HER2+).

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Aims: Fulvestrant is a selective oestrogen receptor (ER) degrader used in postmenopausal women with hormone receptor-positive advanced breast cancer. The study aim was to analyse demographics and outcomes of UK patients treated with fulvestrant monotherapy at nine representative centres.

Materials And Methods: Medical records of 459 patients with locally advanced or metastatic ER-positive, HER2-negative breast cancer treated with fulvestrant between August 2011 and November 2018 at nine UK centres were reviewed.

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