Understanding cardiac events in breast cancer (UCARE): pilot cardio-oncology assessment and surveillance pathway for breast cancer patients.

PURPOSE: In Ireland, over 3000 patients are diagnosed with breast cancer annually, and 1 in 9 Irish women will be diagnosed with breast cancer in their lifetime. There is evidence that female breast cancer survivors are more likely to die of cardiovascular disease than their age-matched counterparts. Specific services for cancer patients suffering from cancer therapy related cardiovascular toxicity have led to a higher incidence of safe anti-cancer treatment completion. Such services are not widely available in our jurisdiction, and the purpose of this trial is to remedy this situation. METHODS: This protocol describes a prospective, single arm, pilot feasibility study implementing a dedicated Cardio-Oncology assessment and surveillance pathway for patients receiving multimodal breast cancer treatment. It incorporates novel biomarker and radiomic surveillance and monitoring approaches for cancer-therapy related cardiac dysfunction into routine care for breast cancer patients undergoing adjuvant systemic chemotherapy. RESULTS: Declaration of results will via peer reviewed academic journals, and communicated directly to key knowledge users both nationally and internationally. This engagement will be critical to enable to healthcare services and policy sector make informed decisions or valuable changes to clinical practice, expenditure and/or systems development to support specialized Cardio-Oncology clinical pathways. All data is to be made available upon request. CONCLUSION: Dedicated cardio-oncology services have been recommended in recent literature to improve patient outcomes. Our protocol describes a feasibility study into the provision of such services for breast cancer.

Circulating microRNAs can predict chemotherapy-induced toxicities in patients being treated for primary breast cancer.

PURPOSE: Prescribing NAC for breast cancer is a pragmatic treatment strategy for several reasons; however, certain patients suffer chemotherapy-induced toxicities. Unfortunately, identifying patients at risk of toxicity often proves challenging. MiRNAs are small non-coding RNA molecules which modulate genetic expression. The aim of this study was to determine whether circulating miRNAs are sensitive biomarkers that can identify the patients likely to suffer treatment-related toxicities to neoadjuvant chemotherapy (NAC) for primary breast cancer. METHODS: This secondary exploratory from the prospective, multicentre translational research trial (CTRIAL ICORG10/11-NCT01722851) recruited 101 patients treated with NAC for breast cancer, from eight treatment sites across Ireland. A predetermined five miRNAs panel was quantified using RQ-PCR from patient bloods at diagnosis. MiRNA expression was correlated with chemotherapy-induced toxicities. Regression analyses was performed using SPSS v26.0. RESULTS: One hundred and one patients with median age of 55 years were recruited (range: 25-76). The mean tumour size was 36 mm and 60.4% had nodal involvement (n = 61) Overall, 33.7% of patients developed peripheral neuropathies (n = 34), 28.7% developed neutropenia (n = 29), and 5.9% developed anaemia (n = 6). Reduced miR-195 predicted patients likely to develop neutropenia (P = 0.048), while increased miR-10b predicted those likely to develop anaemia (P = 0.049). Increased miR-145 predicted those experiencing nausea and vomiting (P = 0.019), while decreased miR-21 predicted the development of mucositis (P = 0.008). CONCLUSION: This is the first study which illustrates the value of measuring circulatory miRNA to predict patient-specific toxicities to NAC. These results support the ideology that circulatory miRNAs are biomarkers with utility in predicting chemotherapy toxicity as well as treatment response.

Comparing surgical outcomes of approaches to adrenalectomy - a systematic review and network meta-analysis of randomised clinical trials.

BACKGROUND: No randomised clinical trials (RCTs) have simultaneously compared the safety of open (OA), transperitoneal laparoscopic (TLA), posterior retroperitoneal (PRA), and robotic adrenalectomy (RA) for resecting adrenal tumours. AIM: To evaluate outcomes for OA, TLA, PRA, and RA from RCTs. METHODS: A NMA was performed according to PRISMA-NMA guidelines. Analysis was performed using R packages and Shiny. RESULTS: Eight RCTs with 488 patients were included (mean age: 48.9 years). Overall, 44.5% of patients underwent TLA (217/488), 37.3% underwent PRA (182/488), 16.4% underwent RA (80/488), and just 1.8% patients underwent OA (9/488). The mean tumour size was 35 mm in largest diameter with mean sizes of 44.3 mm for RA, 40.9 mm for OA, 35.5 mm for TLA, and 34.4 mm for PRA (P < 0.001). TLA had the lowest blood loss (mean: 50.6 ml), complication rates (12.4%, 14/113), and conversion to open rates (1.3%, 2/157), while PRA had the shortest intra-operative duration (mean: 94 min), length of hospital stay (mean: 3.7 days), lowest visual analogue scale pain scores post-operatively (mean: 3.7), and was most cost-effective (mean: 1728 euros per case). At NMA, there was a significant increase in blood loss for OA (mean difference (MD): 117.00 ml (95% confidence interval (CI): 1.41-230.00)) with similar blood loss observed for PRA (MD: - 10.50 (95% CI: - 83.40-65.90)) compared to TLA. CONCLUSION: LTA and PRA are important contemporary options in achieving favourable outcomes following adrenalectomy. The next generation of RCTs may be more insightful for comparison surgical outcomes following RA, as this approach is likely to play a future role in minimally invasive adrenalectomy. PROSPERO REGISTRATION: CRD42022301005.

The impact of liver resection on survival for patients with metastatic breast cancer - A systematic review and meta-analysis.

INTRODUCTION: There is uncertainty surrounding the role of resection as an option for curative treatment of breast cancer with liver metastases (BCLM). AIM: To perform a systematic review and meta-analysis evaluating the role of liver resection for BCLM. METHODS: A systematic review was performed as per PRISMA guidelines. Hazard ratio (HR) for overall survival (OS) and standard error was obtained from each study and expressed using the generic inverse variance method, with a corresponding 95% confidence interval (CI). OS outcomes at 1- 3- and 5-years were expressed as dichotomous variables and pooled as odds ratios (OR) using the Mantel-Haenszel method. RESULTS: Nine studies with 1732 patients were included. Of these, 24.5% underwent surgical resection of BCLM (424/1732) and 75.5% did not (1308/1732). Overall, OS was significantly better among those who underwent surgery versus controls (HR: 0.69, 95% CI: 0.59-0.80, P < 0.00001). Mortality rates were significantly reduced at 1-year (7.5% (10/134) vs 20.3% (79/390), OR: 0.25, 95% CI: 0.08-0.74, P = 0.010) and 5-years (54.0% (190/352) vs 75.3% (940/1249), OR: 0.46, 95% CI: 0.25-0.87, P = 0.020) respectively for those undergoing surgery versus controls. Mortality rates at 3 years after surgery were lower than the control group (19.1% (29/152) vs 53.0% (222/419)), however this failed to achieve statistical significance at meta-analysis (OR: 0.32, 95% CI: 0.09-1.12, P = 0.070). CONCLUSION: Liver resection may be considered at multidisciplinary meetings for those with BCLM and offers a potentially curative option. However, judicious patient selection is crucial prior to making decisions in relation to resection of BCLM.

The role of tranexamic acid in reducing post-operative bleeding and seroma formation in breast surgery: A meta-analysis.

INTRODUCTION: Tranexamic acid (TXA) reduces blood loss and blood transfusion requirements in surgery. Seroma and haematoma formation occur as complications of breast surgery. We aimed to perform a meta-analysis evaluating TXA in reducing post-operative haematoma and seroma formation for breast surgery. METHODS: A systematic review was performed in accordance with PRISMA guidelines. Results were expressed as dichotomous variables pooled as odds ratios (OR) with corresponding 95% confidence intervals (CIs) using the Mantel-Haenszel method. RESULTS: Seven studies including 1446 patients were included. There were 1830 breast surgery procedures performed with TXA administered in 797 cases (43.6%). There was a significant reduction in haematoma rates in the TXA group (TXA: 3.184% (22/691) vs Control: 6.787% (64/943), OR: 0.41, 95% CI: 0.20-0.86, P = 0.020). Based on surgical procedure, haematoma rates were similar for TXA and control groups in cancer surgery (P = 0.230). Haematoma rates reduced following TXA use in cosmetic procedures (TXA: 3.807% (15/394) vs. Control: 9.091% (34/374), OR: 0.41, 95% CI: 0.22-0.75, P = 0.004). Haematoma rates were also reduced in procedures where axillary lymph node dissection (ALND) was not performed; in the TXA group, 3.379% (22/651) developed a haematoma versus 6.623% (60/906) in the control group (OR: 0.45, 95% CI 0.27-0.77, P = 0.003). TXA administration did not impact seroma formation or infection rates. CONCLUSION: Perioperative administration of TXA may impact the incidence of haematoma in breast surgery, particularly in cosmetic procedures and procedures without ALND. Well-designed randomised studies are required to determine its true efficacy. TXA has no effect on seroma formation or infection in breast surgery.

Evaluating the Role of Circulating MicroRNAs to Aid Therapeutic Decision Making for Neoadjuvant Chemotherapy in Breast Cancer: A Prospective, Multicenter Clinical Trial.

OBJECTIVE: To evaluate whether circulating micro ribonucleic acids (miRNAs) predict response to neoadjuvant chemotherapy (NAC) and inform decision-making in breast cancer patients. INTRODUCTION: Deciphering response to NAC remains a challenge. Those unlikely to respond may benefit from NAC de-escalation before completion, while "responders" should complete treatment. Establishing biomarkers which identify response to NAC is imperative to personalize treatment strategies. miRNAs are small noncoding RNA molecules which modulate genetic expression. miRNAs are believed to inform response to NAC. METHODS: This prospective, multicenter trial (NCT01722851) recruited 120 patients treated with NAC across 8 Irish treatment sites. Predetermined miRNAs were quantified from patient whole bloods using relative quantification polymerase chain reactiond. Venous sampling was performed at diagnosis and midway during NAC. Trends in miRNA expression between timepoints were correlated with treatment response. Data analysis was performed using R 3.2.3. RESULTS: A total of 120 patients were included (median age: 55 years). Overall, 49.2% had luminal breast cancers (59/120), 17.5% luminal B (L/HER2) (21/120), 12.5% human epidermal growth factor receptor-2 positive (HER2+) (15/120), and 20.8% triple negative disease (25/120). In total, 46.7% of patients responded to NAC (56/125) and 26.7% achieved a pathological complete response (pCR) (32/120). For patients with L/HER2, increased Let-7a predicted response to NAC ( P =0.049), while decreased miR-145 predicted response to NAC in HER2+ ( P =0.033). For patients with luminal breast cancers, reduced Let-7a predicted achieving a pCR ( P =0.037) and reduced miR-145 predicted achieving a pCR to NAC in HER2+ ( P =0.027). CONCLUSIONS: This study illustrates the potential value of circulatory miRNA measurement in predicting response to NAC. Further interrogation of these findings may see miRNAs personalize therapeutic decision-making for patients undergoing NAC for early breast cancer.

Value of the 21-gene expression assay in predicting locoregional recurrence rates in estrogen receptor-positive breast cancer: a systematic review and network meta-analysis.

PURPOSE: The Oncotype DX© 21-gene Recurrence Score (RS) estimates the risk of distant disease recurrence in early-stage estrogen receptor-positive, human epidermal growth factor receptor-2-negative (ER+/HER2- ) breast cancer. Using RS to estimate risk of locoregional recurrence (LRR) is less conclusive. We aimed to perform network meta-analysis (NMA) evaluating the RS in estimating LRR in ER+/HER2- breast cancer. METHODS: A NMA was performed according to PRISMA-NMA guidelines. Analysis was performed using R packages and Shiny. RESULTS: 16 studies with 21,037 patients were included (mean age: 55.1 years (range: 22-96)). The mean RS was 17.1 and mean follow-up was 66.4 months. Using traditional RS cut-offs, 49.7% of patients had RS < 18 (3944/7935), 33.8% had RS 18-30 (2680/7935), and 16.5% had RS > 30 (1311/7935). Patients with RS 18-30 (risk ratio (RR): 1.76, 95% confidence interval (CI): 1.32-2.37) and RS > 30 (RR: 3.45, 95% CI: 2.63-4.53) were significantly more likely to experience LRR than those with RS < 18. Using TAILORx cut-offs, 16.2% of patients had RS < 11 (1974/12,208), 65.8% had RS 11-25 (8036/12,208), and 18.0% with RS > 30 (2198/12,208). LRR rates were similar for patients with RS 11-25 (RR: 1.120, 95% CI: 0.520-2.410); however, those with RS > 25 had an increased risk of LRR (RR: 2.490, 95% CI: 0.680-9.390) compared to those with RS < 11. There was a stepwise increase in LRR rates when applying traditional and TAILORx cut-offs (both P < 0.050). CONCLUSION: RS testing accurately estimates LRR risk for patients being treated for early-stage ER+/HER2- breast cancer. Future prospective, randomized studies may validate the predictive value of RS in estimating LRR.

Hypocalcaemia following thyroidectomy among patients who have previously undergone bariatric surgery: systematic review and meta-analysis.

BACKGROUND: Hypocalcaemia is a common complication after thyroidectomy. Bariatric surgery is associated with significant changes in calcium metabolism. Some studies have identified bariatric surgery as a risk factor for hypocalcaemia after thyroidectomy. This systematic review and meta-analysis assessed whether a history of bariatric surgery was associated with an increased risk of hypocalcaemia after thyroidectomy. METHODS: This prospectively registered systematic review (PROSPERO; CRD42021295423) was performed in accordance with PRISMA guidelines. Meta-analysis was undertaken using the Mantel-Haenszel method, with outcomes reported as ORs with 95 per cent confidence intervals. RESULTS: Twenty studies were included in the qualitative synthesis. Five studies incorporating 19 547 patients met the inclusion criteria for meta-analysis, of whom 196 (1.0 per cent) had a history of bariatric surgery. Patients with a history of bariatric surgery were more likely to develop hypocalcaemia after thyroidectomy (30.6 versus 13.0 per cent; OR 3.90, 95 per cent c.i. 1.50 to 10.12; P = 0.005). Among those with a history of bariatric surgery, patients who underwent a bypass procedure were more likely to develop hypocalcaemia after thyroidectomy than those who had a restrictive procedure (38 versus 23 per cent; OR 2.12, 1.14 to 3.97; P = 0.020). CONCLUSION: Patients with a history of bariatric surgery have a significantly greater risk of hypocalcaemia after thyroidectomy, with a heightened risk among those who have had a bypass procedure. Surgeons performing thyroid surgery should be aware of the increased risk of hypocalcaemia after thyroidectomy among these patients.

Low calcium levels are a common complication after surgical removal of the thyroid gland. Patients who have had weight loss surgery (bariatric surgery) have altered calcium metabolism and are prone to low calcium levels. This study assessed whether previous weight loss surgery increased the risk of low calcium levels after thyroid surgery. A search was made of previously published studies assessing the relationship between previous weight loss surgery and low calcium levels after thyroid surgery. Studies have shown that previous weight loss surgery makes patients more than three times more likely to have low calcium levels after thyroid surgery. Management of low calcium in these patients is more challenging than in patients who have not had weight loss surgery. Surgeons performing thyroid surgery need to be aware of whether a patient has previously had weight loss surgery as they have an increased risk of low calcium after thyroid surgery.

Genetic and RNA-related molecular markers of trastuzumab-chemotherapy-associated cardiotoxicity in HER2 positive breast cancer: a systematic review.

Cancer-therapy related cardiotoxicity (CTRCT) is a significant and frequent complication of monoclonal antibody directed therapy, especially Trastuzumab, for human epidermal growth factor receptor 2 (HER2) overexpressing breast cancers. Reliable, clinically available molecular predictive markers of CTRCT have not yet been developed. Identifying specific genetic variants and their molecular markers, which make the host susceptible to this complication is key to personalised risk stratification. A systematic review was conducted until April 2021, using the Medline, Embase databases and Google Scholar, to identify studies genetic and RNA-related markers associated with CTRCT in HER2 positive breast cancer patients. So far, researchers have mainly focused on HER2 related polymorphisms, revealing codons 655 and 1170 variants as the most likely SNPs associated with cardiotoxicity, despite some contradictory results. More recently, new potential genetic markers unrelated to the HER2 gene, and linked to known cardiomyopathy genes or to genes regulating cardiomyocytes apoptosis and metabolism, have been detected. Moreover, microRNAs are gaining increasing recognition as additional potential molecular markers in the cardio-oncology field, supported by encouraging preliminary data about their relationship with cardiotoxicity in breast cancers. In this review, we sought to synthesize evidence for genetic variants and RNA-related molecular markers associated with cardiotoxicity in HER2-positive breast cancer.

Intra-operative nerve monitoring and recurrent laryngeal nerve injury during thyroid surgery: a network meta-analysis of prospective studies.

PURPOSE: Recurrent laryngeal nerve (RLN) injury is a feared complication of thyroid surgery occurring in 1-5% of cases. The present approaches to RLN preservation include RLN visualization with no nerve monitoring (No-NM), intermittent intra-operative nerve monitoring (I-IONM) and continuous intra-operative nerve monitoring (C-IONM). There is ambiguity as to which of these strategies should be the preferred method of RLN preservation. METHODS: A systematic review of the PubMed, Embase and the Cochrane Collaboration databases was undertaken with network meta-analysis (NMA) performed according to the PRISMA and Cochrane Collaboration guidelines. A Bayesian NMA was conducted using R packages netmeta with outcomes expressed as odds ratios (ORs) with 95% credible intervals (CrI). Only prospective studies were included. RESULTS: Eighteen studies met inclusion criteria, including 22,080 patients and 40,642 nerves at risk (NAR). Overall, 23,364 NARs (57.5%) underwent I-IONM, 17,176 (42.3%) No-NM and 98 (0.2%) underwent C-IONM. There were no significant differences between groups regarding the incidence of permanent RLN injury following thyroid surgery (I-IONM vs.No-NM, OR 0.84, 95% CrI 0.55-1.19; C-IONM vs. No-NM, OR 0.44, 95% CrI 0.02-5.00). Pooled analysis showed that IONM (I-IONM or C-IONM) demonstrated a protective effect versus No-NM in reducing the incidence of transient RLN injury (OR 0.75, 95% CI 0.59-0.97, p = 0.03). CONCLUSIONS: IONM strategies did not significantly reduce the incidence of permanent RLN injury following thyroid surgery. However, the small number of C-IONM NARs limits conclusions that may be drawn. Further well-designed prospective studies will be required to definitively assess the utility of C-IONM.

A radiomic model to classify response to neoadjuvant chemotherapy in breast cancer.

BACKGROUND: Medical image analysis has evolved to facilitate the development of methods for high-throughput extraction of quantitative features that can potentially contribute to the diagnostic and treatment paradigm of cancer. There is a need for further improvement in the accuracy of predictive markers of response to neo-adjuvant chemotherapy (NAC). The aim of this study was to develop a radiomic classifier to enhance current approaches to predicting the response to NAC breast cancer. METHODS: Data on patients treated for breast cancer with NAC prior to surgery who had a pre-NAC dynamic contrast enhanced breast MRI were included. Response to NAC was assessed using the Miller-Payne system on the excised tumor. Tumor segmentation was carried out manually under the supervision of a consultant breast radiologist. Features were selected using least absolute shrinkage selection operator regression. A support vector machine learning model was used to classify response to NAC. RESULTS: 74 patients were included. Patients were classified as having a poor response to NAC (reduction in cellularity < 90%, n = 44) and an excellent response (> 90% reduction in cellularity, n = 30). 4 radiomics features (discretized kurtosis, NGDLM contrast, GLZLM_SZE and GLZLM_ZP) were identified as pertinent predictors of response to NAC. A SVM model using these features stratified patients into poor and excellent response groups producing an AUC of 0.75. Addition of estrogen receptor status improved the accuracy of the model with an AUC of 0.811. CONCLUSION: This study identified a radiomic classifier incorporating 4 radiomics features to augment subtype based classification of response to NAC in breast cancer.

Grit personality trait of doctors and medical students in level 4 acute hospital.

INTRODUCTION: GRIT, defined as passion and perseverance for long-term goals, is a personality trait that is key to academic success and career achievement. Doctors face significant challenges and exposure to stressful situations throughout their career and require high levels of grit and perseverance to achieve success and avoid burn-out. This study aimed to measure overall levels of grit among hospital doctors and medical students and to compare levels of Grit across specialties and career grades. METHOD: ology: A cross-sectional survey was used to measure GRIT levels using the validated Short Grit Scale (GRIT-S). Hospital doctors and medical students at University Hospital Galway were asked to complete the questionnaire. Gender, age, grade, education, and speciality were recorded. Analysis was conducted using STATA V12.1™ and SPSS 25™. RESULTS: 378 questionnaires were completed with a participation rate of 75.6% eligible for analysis. The female: male ratio was 1.2:1, with a mean age of 29.6 ± 8.3 years. The mean Grit score of participants was 3.56 ± 0.55. Grit trait was independent of gender and increased with age and grade. Consultants had significantly higher mean Grit score (3.86 ± 0.59, p = 0.004). There was no difference between medical specialities, nor between graduate-entry and undergraduate medical students. CONCLUSION: our results show that medical students and NCHDs alike have high levels of Grit compared to the general population, and the levels increase with career advancement, with the highest scores observed in consultants. This suggests that Grit might be of benefit as an adjunct in the selection process of applicants for training schemes and jobs that require high levels of resilience, as well as an adjunct to monitoring progress in training from a personality and mental health perspective.

Clinicopathological correlates, oncological impact, and validation of Oncotype DX™ in a European Tertiary Referral Centre.

Oncotype DX™ (ODX) score estimates prognosis and predicts breast cancer recurrence. It also individualizes patient adjuvant chemotherapy prescription in breast cancer. This assay relies on genetic and molecular markers; the clinicopathological phenotype of which are tested routinely. The aim of this study was determine whether clinicopathological and immunohistochemical information predicts ODX recurrence score (RS). Secondly, to assess the impact on adjuvant chemotherapy (AC) and oncological outcome of ODX testing in patients in a European tertiary referral center. Estrogen receptor positive (ER+), human epidermal growth factor receptor-2 negative (HER2-), lymph node negative (LN-), and female breast cancer patients with ODX testing performed between 2007 and 2015 were categorized into low- (<11), intermediate- (11-25), and high-risk (>25) groups. Clinicopathological and immunohistochemical correlates of RS were determined. Predictors of RS were assessed using binary logistic regression. Oncological outcome was assessed using Kaplan-Meier and Cox regression analyses. ODX was performed in 400 consecutive ER+LN- patients. Median follow-up was 74.1 months (3.0-144.4). Low grade (odds ratio [OR]:2.39; 95% confidence interval [CI]:1.04-5.51, p = 0.041) independently predicted low ODX, while high grade (OR:2.04; 95% CI: 1.19-3.49, p = 0.009) and reduced progesterone receptor (PgR) expression (OR: 2.57, 95% CI: 1.42-4.65, p = 0.002) independently predicted high ODX. Omission of AC in intermediate- (p = 0.159) and high-risk (p = 0.702) groups did not negatively impact survival. In conclusion, tumor grade independently predicts low and high RS, while PgR negativity predicts high RS. ODX reduced AC prescription without compromising oncological outcome.

MicroRNA Expression Profiles and Breast Cancer Chemotherapy.

Breast cancer is the most common malignancy diagnosed in women. Traditionally, radical surgical resection was the cornerstone of breast cancer management, with limited exceptions. In recent times, our enhanced appreciation of the biomolecular characteristics of breast cancer has transformed the treatment paradigm to include prescription of chemotherapeutical agents, radiotherapies, targeted therapies, as well as more refined surgical approaches. While treatments with such modalities have enhanced clinico-oncological outcomes for breast cancer patients, the efforts of oncological and translational research have concentrated on the identification of novel biomarkers which may successfully inform prognosis and response to therapies, improve current therapeutic strategies, and enhance prognostication. Mi(cro)RNAs are small, non-coding molecules which are known to play regulatory roles in governing gene expression and cellular activity. Measurement of miRNA expression profiles have been illustrated to inform the response to therapies, such as conventional chemotherapy, and are currently undergoing assessment as means of enhancing treatment strategies with these cytotoxic agents. Herein, this review outlines how chemotherapy prescription has revolutionised breast cancer treatment and illustrates the novel role of miRNAs as biomarkers capable of enhancing current therapeutic strategies using chemotherapy in patients being treated with curative intent for breast cancer.

The Role of MicroRNA as Clinical Biomarkers for Breast Cancer Surgery and Treatment.

Breast cancer is the most common cancer diagnosed in women. In recent times, survival outcomes have improved dramatically in accordance with our enhanced understanding of the molecular processes driving breast cancer proliferation and development. Refined surgical approaches, combined with novel and targeted treatment options, have aided the personalisation of breast cancer patient care. Despite this, some patients will unfortunately succumb to the disease. In recent times, translational research efforts have been focused on identifying novel biomarkers capable of informing patient outcome; microRNAs (miRNAs) are small non-coding molecules, which regulate gene expression at a post-transcriptional level. Aberrant miRNA expression profiles have been observed in cancer proliferation and development. The measurement and correlation of miRNA expression levels with oncological outcomes such as response to current conventional therapies, and disease recurrence are being investigated. Herein, we outline the clinical utility of miRNA expression profiles in informing breast cancer prognosis, predicting response to treatment strategies as well as their potential as therapeutic targets to enhance treatment modalities in the era of precision oncology.

The histopathological and molecular features of breast carcinoma with tumour budding-a systematic review and meta-analysis.

PURPOSE: Tumour budding (TB) is an adverse histological feature in many epithelial cancers. It is thought to represent epithelial-mesenchymal transition, a key step in the metastatic process. The significance of TB in breast carcinoma (BC) remains unclear. The aim of this study is to investigate the relationship between TB and other histological and molecular features of BC. METHODS: A systematic search was performed to identify studies that compared features of BC based on the presence or absence of high-grade TB. Dichotomous variables were pooled as odds ratios (OR) using the Der Simonian-Laird method. Quality assessment of the included studies was performed using the Newcastle-Ottawa scale (NOS). RESULTS: Seven studies with a total of 1040 patients (high-grade TB n = 519, 49.9%; low-grade/absent TB n = 521, 50.1%) were included. A moderate to high risk of bias was noted. The median NOS was 7 (range 6-8). High-grade TB was significantly associated with lymph node metastasis (OR 2.32, 95% c.i. 1.77 to 3.03, P < 0.001) and lymphovascular invasion (OR 3.08, 95% c.i. 2.13 to 4.47, P < 0.001). With regard to molecular subtypes, there was an increased likelihood of high-grade TB in oestrogen (OR 1.66, 95% c.i. 1.21 to 2.29, P = 0.002) and progesterone receptor-positive (OR 1.48, 95% c.i. 1.09 to 2.02, P = 0.01) tumours. In contrast, triple-negative breast cancer had a reduced incidence of high-grade TB (OR 0.46, 95% c.i. 0.30 to 0.72, P = 0.0006). CONCLUSION: High-grade TB is enriched in hormone receptor-positive BC and is associated with known adverse prognostic variables. TB may offer new insights into the metastatic process of BC.

11 C-Metomidate PET/CT is a useful adjunct for lateralization of primary aldosteronism in routine clinical practice.

OBJECTIVE: To describe clinical practice experience of 11 C-Metomidate PET/CT as an adjunct to adrenal vein sampling (AVS) in the lateralization of aldosterone-producing adenomas (APA) in primary aldosteronism (PA). CONTEXT: Accurate lateralization of APA in the setting of PA offers the potential for surgical cure and improved long-term cardiovascular outcomes. Challenges associated with AVS, the current gold standard lateralization modality, mean that only a small proportion of potentially eligible patients currently make it through to surgery. This has prompted consideration of alternative strategies for lateralization, including the application of novel molecular PET tracers such as 11 C-Metomidate. DESIGN: Clinical Service Evaluation/Retrospective audit. PATIENTS: Fifteen individuals with a confirmed diagnosis of PA, undergoing lateralization with 11 C-Metomidate PET/CT prior to final clinical decision on surgical vs medical management. MEASUREMENTS: All patients underwent screening aldosterone renin ratio (ARR), followed by confirmatory testing with the seated saline infusion test, according to Endocrine Society Clinical Practice Guidelines. Adrenal glands were imaged using dedicated adrenal CT. 11 C-Metomidate PET/CT was undertaken due to equivocal or failed AVS. Management outcomes were assessed by longitudinal measurement of blood pressure, ARR, number of hypertensive medications following adrenalectomy or institution of medical therapy. RESULTS: We describe the individual lateralization and clinical outcomes for 15 patients with PA. CONCLUSION: 11 C-Metomidate PET/CT in conjunction with adrenal CT and AVS provided useful information which aided clinical decision-making for PA within a multidisciplinary hypertension clinic.

Six-year review of traumatic brain injury in a regional trauma unit: demographics, contributing factors and service provision in Ireland.

BACKGROUND: Traumatic brain injury (TBI) represents a significant burden of care for acute surgical services, particularly in the absence of on-site neurosurgical cover or sufficient post-acute rehabilitation facilities. We examine factors contributing to TBI, prolonged lengths of stay (LoS) and implications for hospital resources. Long-term outcomes are assessed. METHODS: This is a retrospective cohort study of patients admitted to a regional trauma unit with TBI from 2008 to 2013. Patients with LoS > 48 h were assessed. Demographic, clinical and longitudinal mortality data were collected using electronic clinical and radiological systems and chart review. RESULTS: A total of 690 patients presented with TBI from 2008 to 2013; 213 patients with LoS > 48 h were assessed. One hundred and thirty (61%) were male. Mean age was 56 years (±SD 24). Mechanical fall was the most frequent injury mechanism (n = 120/213, 56%). Twenty-five per cent were associated with alcohol consumption; these were more likely to be male, involved in an Road Traffic Accident (RTA) or assault and necessitate transfer to a neurosurgical unit (p < 0.001, p = 0.029, p < 0.001, p = 0.05). A total of 112 patients(53%) had a prolonged LoS (>2 weeks). Mean LoS was 20 days (±SD 35), increasing to 39 days for patients requiring neurosurgical intervention. The 12-month all-cause mortality rate was 12%. CONCLUSIONS: TBIs result in significant utilisation of acute inpatient bed days. Improved rehabilitation services and strategies to reduce acute hospital LoS are warranted.

Differential impact of hormone receptor status on survival and recurrence for HER2 receptor-positive breast cancers treated with Trastuzumab.

INTRODUCTION: Hormone receptor status has major implications for treatment and survival of breast cancer. Yet the impact of hormone receptor status on outcome after Trastuzumab has received little attention. The objective here was to explore any differential effects of Trastuzumab treatment (Trast +ve) on Luminal B HER2 or HER2+(ER-) breast cancer subtypes. METHODS: A cohort of 469 HER2 receptor-positive breast cancers was categorised by molecular subtype and Trastuzumab treatment. Effects of Trastuzumab treatment on survival, locoregional recurrence and distant metastasis were investigated by subtype, using univariate and multivariate analysis. RESULTS: Trast +ve Luminal B HER2 patients had significant improvements in 5-year DFS (p < 0.001) and OS (p < 0.001), while Trast +ve HER2+(ER-) patients had significant improvements in 5-year DFS (p = 0.012) alone. Only Trast +ve Luminal B HER2 cancers displayed a significant reduction in LRR rates (p < 0.001). A significant reduction in distant metastasis rates was seen in Trast +ve Luminal B HER2 (p < 0.001) and HER2+(ER-) (p = 0.009) cancers. Interestingly, bone metastasis rates in Trast +ve Luminal B HER2 cancers demonstrated the greatest reduction (36.2-6.7%). Multivariate analysis of Trast +ve patients found no difference in distant metastasis rates (p = 0.96) between subtypes. Significantly, lower LRR rates were seen in Trast +ve Luminal B HER2 cancers, compared to Trast +ve HER2+(ER-) (p = 0.018). CONCLUSION: An enhanced response to Trastuzumab was seen in Luminal B HER2 cancers. We highlight how Trastuzumab treatment changed the natural history of the HER2 receptor-positive breast cancer, demonstrating improved efficacy in changing the outcome of hormone receptor-positive patients.

Locoregional Recurrence Following Breast Cancer Surgery in the Trastuzumab Era: A Systematic Review by Subtype.

INTRODUCTION: Increasing evidence suggests that molecular subtype influences locoregional recurrence (LRR) of breast cancer. Previous systematic reviews that evaluated the quantitative influence of subtype on LRR predated the use of Trastuzumab. This study assessed the impact of subtype on LRR in a contemporary treatment era. METHODS: A comprehensive search for all published studies assessing LRR according to breast cancer subtype was performed. Only studies with patients treated with Trastuzumab were included. Relevant data were extracted from each study for systematic review. Primary outcome was LRR related to breast cancer subtype. RESULTS: In total, 11,219 patients were identified from seven studies. Overall LRR rate was 3.44%. The lowest LRR rates were in luminal A (1.7%), and the highest rates were in triple-negative (7.4%) subtypes. There were significantly lower risks of LRR in patients with luminal A subtype compared with luminal B [odds ratio (OR) 0.54, 95% confidence interval (CI) 0.38-0.76; p < 0.0004], HER2/neu-overexpressing (OR 0.32, 95% CI 0.24-0.45; p < 0.0001) and triple-negative breast cancers (OR 0.25, 95% CI 0.19-0.32; p < 0.0001). There were significant differences in LRR between the luminal B and HER2/neu-overexpressing breast cancers (OR 0.61, 95% CI 0.41-0.89; p = 0.0145). The reduced risk in HER2/neu overexpressing compared with triple-negative breast cancers approached statistical significance (OR 0.75, 95% CI 0.55-1.03; p = 0.0933). CONCLUSIONS: Significant variations in LRR occur across breast cancer subtypes, with lowest rates in luminal cancers and highest rates in triple-negative breast cancers. Low levels of LRR highlight advances in breast cancer management in the contemporary era.