Arran K Turnbull

Arran K Turnbull
The University of Edinburgh | UoE · Edinburgh Cancer Research UK Centre

BSc(Hons), MSc(Res), PhD

About

164
Publications
11,024
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Introduction
I am a postdoctoral research fellow leading a lab-based research team at the University of Edinburgh. My research focuses on understanding, predicting and treating resistance to endocrine therapy in breast cancer. I completed my undergraduate honours degree in molecular biology at Heriot-Watt University and then a masters by research in immunology and genetics at the University of Edinburgh. I graduated with a PhD in oncology from the University of Edinburgh in 2012. In 2014 I went on to study medicine at the University of Glasgow. In my PhD I developed a clinical predictive test for endocrine therapy response in breast cancer for which I and my colleagues hold the UK patent. I am also the lead investigator of projects on DCIS, radiotherapy, microwave radiometry and prostate cancer.
Additional affiliations
September 2014 - present
The University of Edinburgh
Position
  • Lecturer
January 2013 - present
The University of Edinburgh
Position
  • PostDoc Position
Education
September 2009 - April 2013
The University of Edinburgh
Field of study
  • Clinical and Molecular Medicine
September 2006 - August 2007
The University of Edinburgh
Field of study
  • Genetics and Pathway Medicine
September 2003 - June 2006
Heriot-Watt University
Field of study
  • Molecular Biology

Publications

Publications (164)
Preprint
Ovarian cancer is the third most common female genital cancer. Therefore, the timely diagnosis and comprehensive treatment of postmenopausal patients with benign ovarian tumors remains crucial in the field of gynecology. The significance of ovarian tumors depends on their frequency and their effects on the quality of life of a woman, as well as the...
Article
Purpose: Endocrine therapy resistance (ETR) remains the greatest challenge in treating patients with hormone receptor-positive breast cancer. We set out to identify molecular mechanisms underlying ETR through in-depth genomic analysis of breast tumors. Experimental design: We collected pre-treatment and sequential on-treatment tumor samples from...
Article
Background: Neoadjuvant chemotherapy (NACT) for breast cancer is given prior to surgery, aiming to reduce tumour burden and provide early information on response to treatment. Tumours with a pathological complete response (pCR) following NACT are less likely to recur than those in patients with residual disease following NACT, suggesting that pCR f...
Article
Full-text available
Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer, and it exhibits a number of clinico-pathological characteristics distinct from the more common invasive ductal carcinoma (IDC). We set out to identify alterations in the tumor microenvironment (TME) of ILC. We used laser-capture microdissection to sepa...
Article
Full-text available
Primary acinic cell carcinoma (AcCC) is a rare histological type of malignant breast cancer. AcCC was first identified as an entity in 1996, and since then 51 cases have been reported in the literature. The first early case reports and reviews suggested a relatively favourable prognosis for patients with AcCC; however, reports of AcCC recurrent dis...
Article
Full-text available
IL6-like cytokines are a family of regulators with a complex, pleiotropic role in both the healthy organism, where they regulate immunity and homeostasis, and in different diseases, including cancer. Here we summarise how these cytokines exert their effect through the shared signal transducer IL6ST (gp130) and we review the extensive evidence on th...
Article
Full-text available
Radiotherapy (RT) is an important treatment modality for the local control of breast cancer (BC). Unfortunately, not all patients that receive RT will obtain a therapeutic benefit, as cancer cells that either possess intrinsic radioresistance or develop resistance during treatment can reduce its efficacy. For RT treatment regimens to become persona...
Article
Full-text available
Worldwide, prostate cancer (PC) is the second-most-frequently diagnosed male cancer and the fifth-most-common cause of all cancer-related deaths. Suspicion of PC in a patient is largely based upon clinical signs and the use of prostate-specific antigen (PSA) levels. Although PSA levels have been criticised for a lack of specificity, leading to PC o...
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Full-text available
Novel biomarkers are needed to continue to improve breast cancer clinical management and outcome. IL6-like cytokines, whose pleiotropic functions include roles in many hallmarks of malignancy, rely on the signal transducer IL6ST (gp130) for all their signalling. To date, 10 separate independent studies based on the analysis of clinical breast cance...
Article
Treatment for HR+/HER2+ patients has been debated, as some tumors within this luminal HER2+ subtype behave like luminal A cancers, whereas others behave like non-luminal HER2+ breast cancers. Recent research and clinical trials have revealed that a combination of hormone and targeted anti-HER2 approaches without chemotherapy provides long-term dise...
Conference Paper
Background: Palbociclib, with endocrine therapy, has demonstrated clinical benefit in patients with ER+ve HER2-ve metastatic breast cancer in randomised controlled clinical trials. Further observational data is beneficial to illustrate how these results translate into benefit in routine practice. Furthermore, detecting predictors of response aids c...
Article
Introduction Excision biopsy has been the investigation of choice for patients presenting with pathological axillary lymphadenopathy without a breast abnormality. Core biopsy of nodes can provide sufficient tissue for diagnosis and has advantages in terms of morbidity and speed of diagnosis. This study evaluates the diagnostic accuracy of core biop...
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Full-text available
Many patients with ER+ HER2− primary breast cancer are being deferred from surgery to neoadjuvant endocrine therapy (NeoET) during the COVID-19 pandemic. We have collated data from multiple international trials of presurgical endocrine therapy in order to provide guidance on the identification of patients who may have insufficiently endocrine-sensi...
Article
Full-text available
Treating individual patients on the basis of specific factors, such as biomarkers, molecular signatures, phenotypes, environment, and lifestyle is what differentiates the precision medicine initiative from standard treatment regimens. Although precision medicine can be applied to almost any branch of medicine, it is perhaps most easily applied to t...
Article
Full-text available
PurposeThe goal of sentinel lymph node biopsy is to establish the presence or absence of cancer cells in regional axillary nodes. The number of sentinel nodes harvested from each patient varies. The aim of this study was to determine what factors influence the number of sentinel nodes excised at sentinel node biopsy.Methods Data from 426 patients w...
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Purpose: While chemotherapy has improved survival among younger women with breast cancer, it can induce temporary or permanent chemotherapy-related amenorrhoea (CRA), impacting survival benefit, quality of life and, importantly for younger patients, fertility. Methods: This single institution retrospective study of 107 premenopausal women with e...
Preprint
Full-text available
Background: Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer and exhibits a number of clinico-pathological characteristics distinct from the more common invasive ductal carcinoma (IDC). Despite these differences, ILC is treated in the same way as IDC. We set out to identify alterations in the tumor mi...
Article
Full-text available
Research using in vitro canine mammary cancer cell lines and naturally-occurring canine mammary tumors are not only fundamental models used to advance the understanding of cancer in veterinary patients, but are also regarded as excellent translational models of human breast cancer. Human breast cancer is commonly treated with radiotherapy; however,...
Article
Full-text available
Despite extensive research over many decades, human breast cancer remains a major worldwide health concern. Advances in pre-clinical and clinical research has led to significant improvements in recent years in how we manage breast cancer patients. Although survival rates of patients suffering from localized disease has improved significantly, the p...
Preprint
Full-text available
Background Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer and exhibits a number of clinico-pathological characteristics that are distinct from the more common invasive ductal carcinoma (IDC). Despite these differences, ILC is treated in the same way as IDC. We set out to identify alterations in the...
Article
Full-text available
Radiotherapy remains an important treatment modality in nearly two thirds of all cancers, including the primary curative or palliative treatment of breast cancer. Unfortunately, largely due to tumor heterogeneity, tumor radiotherapy response rates can vary significantly, even between patients diagnosed with the same tumor type. Although in recent y...
Conference Paper
BACKGROUND Anthracyclines are widely used in the treatment of breast cancer and are well recognised to carry increased risk of cardiotoxicity. This can occur as an early, acute manifestation or many years after treatment as late onset cardiomyopathy. It is increasingly apparent that there may be a chronic subclinical phase associated with low grade...
Conference Paper
Background: A sentinel lymph node in breast cancer surgery is defined as a blue node or a “hot” radioactive node and includes nodes other than the hottest node providing that they contain at least 10% of the radioactivity of the hottest node. The false negative rate of SLNB in breast cancer surgery falls as the number of sentinel nodes removed incr...
Conference Paper
Background: 80% of all breast cancers (BCs) are ER+. Not all respond to endocrine therapy (ET) and many eventually develop resistance. An in-depth genomic analysis of cancers that acquired resistance (aR) to multiple sequential lines of ET after an initial period of response has been performed. Patients: A unique cohort of tissues from 20 post-meno...
Conference Paper
Background: The ER+/HER2+ subtype accounts for up to 10% of all breast cancers (BCs) and most are treated with surgery followed by adjuvant chemotherapy with Herceptin +/- radiotherapy then adjuvant endocrine therapy (ET) to reduce the recurrence risk. Despite this it is clear that not all ER+/HER2+ patients gain benefit from the addition of chemot...
Conference Paper
Background: Radiotherapy (RT) plays an important role in the multimodal treatment of breast cancer (BC). Despite improvements in the accuracy of delivering radiation to specific biological target volumes, the clinical response of BC to RT is still affected by intrinsic/acquired radioresistance. These resistant cancer cells can contribute to the dev...
Conference Paper
Background: Ductal carcinoma in situ (DCIS) lesions are non-obligate precursors to invasive breast cancer (IBC). With the ultimate goal of preventing the development of invasive disease, DCIS is typically treated by breast-conserving surgery (BCS). Adjuvant radiotherapy (RT) is given for high-grade disease to reduce the risk of in-breast tumour rec...
Conference Paper
Background: Endocrine therapy (ET) is an effective treatment of estrogen receptor positive (ER+) breast cancer (BC). However, not all ER+ cancers respond to ET and many eventually acquire resistance. Genomic aberrations in ESR1 have been reported to play a role in resistance to treatment. ESR1 mutations (ESRMs), reported in 10-50% of metastatic or...
Article
Full-text available
Background: High-throughput transcriptomics has matured into a very well established and widely utilised research tool over the last two decades. Clinical datasets generated on a range of different platforms continue to be deposited in public repositories provide an ever-growing, valuable resource for reanalysis. Cost and tissue availability norma...
Article
Endocrine therapy is important for management of patients with estrogen receptor (ER) positive breast cancer, however positive ER staining does not reliably predict therapy response. We assessed the potential to improve prediction of response to endocrine treatment of a novel test that quantifies functional ER pathway activity from mRNA levels of E...
Article
Background Despite ER positive IHC staining, some patients do not respond to neoadjuvant endocrine therapy, suggesting that ER staining lacks specificity to predict response. We developed a method to infer a quantitative signal transduction pathway activity score (PAS) from mRNA levels (microarray, qPCR) of pathway-associated transcription factor t...
Article
Full-text available
Background: Neoadjuvant chemotherapy is increasingly given preoperatively to shrink breast tumours prior to surgery. This approach also provides the opportunity to study the molecular changes associated with treatment and evaluate whether on-treatment sequential samples can improve response and outcome predictions over diagnostic or excision sampl...
Article
Full-text available
Background Radiotherapy plays an important role in the multimodal treatment of breast cancer. The response of a breast tumour to radiation depends not only on its innate radiosensitivity but also on tumour repopulation by cells that have developed radioresistance. Development of effective cancer treatments will require further molecular dissection...
Article
Introduction Accurate assessment of estrogen receptor (ER) expression is crucial to ensure that patients with early breast cancer are accurately identified for appropriate treatment with endocrine therapy. Reverse transcriptase polymerase chain reaction (RT-PCR), compared with immunohistochemistry (IHC), may provide a more precise indication of ER...
Article
Background:In breast cancer (BC), radiotherapy (RT) is used adjuvantly to prevent recurrence and also in the palliative setting. Clinical signs of RT response are often not apparent for several weeks post-treatment and we currently lack tools to predict or monitor tumor response to RT early during treatment. The aim was to identify tumor-secreted b...
Article
Background: ER+/HER2+ accounts for up to 10% of all breast cancers (BCs) and most are treated with endocrine therapy (ET) after surgery to reduce the recurrence risk. We developed and validated an immunohistochemistry (IHC) based test (EA2Clin) that incorporates baseline IL6ST, clinical variables and on-treatment measurement of MCM4. Responders (Rs...
Article
Full-text available
Background: Transcriptomic analyses of clinical samples can help improve our understanding of disease aetiology, drug effectiveness, assign molecular subtypes and derive prognostic signatures for clinical decision-making. The success of early microarray studies relied heavily on sample quality and predominantly fresh frozen (FF) tissues to generate...
Article
Background: The majority of patients with early-stage estrogen receptor positive (ER+) breast cancer (BC) are treated with adjuvant endocrine therapy (ET) after surgery to reduce the risk of recurrence. Recently, we have developed and validated an immunohistochemistry (IHC) based assay (EndoAdjuvant2 Clinical; EA2Clin) that measures pre-treatment I...
Article
Background Interest in the ubiquitously expressed transmembrane receptor IL6ST (gp130) has developed as it has been identified as a predictive biomarker of endocrine treatment response in breast cancer patients and is included in the 'Endopredict' test. At least seven cytokines (IL-6, OSM, LIF, IL-11, CNTF, IL-27, CT-1) signal via IL6ST. Interleuki...
Article
Background: Ductal carcinoma (DCIS) is a heterogeneous precursor, non-invasive breast lesion. There is a lack of specific DCIS molecular predictors of in breast tumour recurrence (IBTR) or progression to invasive breast cancer (IBC) after breast conserving surgery (BCS) +/- radiotherapy (RT). The aim of this was to identify novel biomarkers and com...
Article
Background: Approximately 70% of breast cancers (BCs) are estrogen receptor positive (ER+). Not all ER+ cancers respond to endocrine therapy (ET) and many eventually develop acquired resistance. Next-generation sequencing (NGS) has shown ESR1 mutations (ESRMs) are present in 10-50% of recurrent/metastatic cancers treated with aromatase inhibitors (...
Article
Background: The risk of recurrence for oestrogen receptor positive (ER+) breast cancer patients treated with 5 years of adjuvant endocrine therapy persists for many years or even decades following surgery and apparently successful adjuvant therapy. This period of dormancy and acquired resistance is inherently difficult to investigate. Therefore, pr...
Article
Background: Late recurrence is characteristic of ER+ breast cancers. Despite an apparently effective adjuvant endocrine therapy, many breast cancers recur years after their initial endocrine treatment. Why some tumors recur early (<3 years) and some recur later (>5 years) is poorly understood. If systemic endocrine therapies killed all cells, recur...
Article
Purpose: Neo-Adjuvant chemotherapy treatment is increasingly being used in breast cancer to preoperatively shrink tumour volumes and facilitate surgical plans. These datasets however, are still scarce, making it difficult to assess the relative value of multiple time point biopsies compared to diagnostic only sampling. This study aims to identify s...
Article
Background: Around 70% of all breast cancers (BCs) are estrogen receptor positive (ER+), but some do not respond to endocrine therapy (ET) and many eventually develop resistance. ESR amplification (ESRA) linked to an increase in ESR1 gene expression is known to occur in some cancers that are endocrine resistant. However, the incidence of ESRA has b...
Article
Background: The role of neoadjuvant endocrine therapy (NET) for ER+ DCIS is an area of evolving study. It may allow down-sizing prior to surgery, converting DCIS requiring mastectomy to disease suitable for breast conservation surgery (BCS). Here we report the results from the first European single-institution series of its type. Methods: Data were...
Article
Full-text available
Background Tumour hypoxia is a driver of breast cancer progression associated with worse prognosis and more aggressive disease. The cellular response to hypoxia is mediated by the hypoxia-inducible transcription factors HIF-1 and HIF-2, whose transcriptional activity is canonically regulated through their oxygen-labile HIF-α subunits. These are con...
Article
Full-text available
Background The risk of recurrence for endocrine-treated breast cancer patients persists for many years or even decades following surgery and apparently successful adjuvant therapy. This period of dormancy and acquired resistance is inherently difficult to investigate; previous efforts have been limited to in-vitro or in-vivo approaches. In this stu...