A pilot study investigating feasibility of mainstreaming germline BRCA1 and BRCA2 testing in high-risk patients with breast and/or ovarian cancer in three tertiary Cancer Centres in Ireland.

In the Republic of Ireland (ROI), BRCA1/BRCA2 genetic testing has been traditionally undertaken in eligible individuals, after pre-test counselling by a Clinical Geneticist/Genetic Counsellor. Clinical Genetics services in ROI are poorly resourced, with routine waiting times for appointments at the time of this pilot often extending beyond a year. The consequent prolonged waiting times are unacceptable where therapeutic decision-making depends on the patient's BRCA status. "Mainstreaming" BRCA1/BRCA2 testing through routine oncology/surgical clinics has been implemented successfully in other centres in the UK and internationally. We aimed to pilot this pathway in three Irish tertiary centres. A service evaluation project was undertaken over a 6-month period between January and July 2017. Eligible patients, fulfilling pathology and age-based inclusion criteria defined by TGL clinical, were identified, and offered constitutional BRCA1/BRCA2 testing after pre-test counselling by treating clinicians. Tests were undertaken by TGL Clinical. Results were returned to clinicians by secure email. Onward referrals of patients with uncertain/pathogenic results, or suspicious family histories, to Clinical Genetics were made by the treating team. Surveys assessing patient and clinician satisfaction were sent to participating clinicians and a sample of participating patients. Data was collected with respect to diagnostic yield, turnaround time, onward referral rates, and patient and clinician feedback. A total of 101  patients underwent diagnostic germline BRCA1/BRCA2 tests through this pathway. Pathogenic variants were identified in 12 patients (12%). All patients in whom variants were identified were appropriately referred to Clinical Genetics. At least 12 additional patients with uninformative BRCA1/BRCA2 tests were also referred for formal assessment by Clinical Geneticist or Genetic Counsellor. Issues were noted in terms of time pressures and communication of results to patients. Results from a representative sample of participants completing the satisfaction survey indicated that the pathway was acceptable to patients and clinicians. Mainstreaming of constitutional BRCA1/BRCA2 testing guided by age- and pathology-based criteria is potentially feasible for patients with breast cancer as well as patients with ovarian cancer in Ireland.

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.

Comparison of the Nottingham Prognostic Index and OncotypeDX© recurrence score in predicting outcome in estrogen receptor positive breast cancer.

INTRODUCTION: Traditionally, Nottingham prognostic index (NPI) informed prognosis in patients with estrogen receptor positive, human epidermal growth factor receptor-2 negative, node negative (ER+/HER2-/LN-) breast cancer. At present, OncotypeDX© Recurrence Score (RS) predicts prognosis and response to adjuvant chemotherapy (AC). AIMS: To compare NPI and RS for estimating prognosis in ER + breast cancer. METHODS: Consecutive patients with ER+/HER2-/LN- disease were included. Disease-free (DFS) and overall survival (OS) were determined using Kaplan-Meier and Cox regression analyses. RESULTS: 1471 patients met inclusion criteria. The mean follow-up was 110.7months. NPI was calculable for 1382 patients: 19.8% had NPI≤2.4 (291/1471), 33.0% had NPI 2.41-3.4 (486/1471), 30.0% had NPI 3.41-4.4 (441/1471), 10.9% had NPI 4.41-5.4 (160/1471), and 0.3% had NPI>5.4 (4/1471). In total, 329 patients underwent RS (mean RS: 18.7) and 82.1% had RS < 25 (270/329) and 17.9% had RS ≥ 25 (59/329). Using multivariable Cox regression analyses (n = 1382), NPI independently predicted DFS (Hazard ratio (HR): 1.357, 95% confidence interval (CI): 1.140-1.616, P < 0.001) and OS (HR: 1.003, 95% CI: 1.001-1.006, P = 0.024). When performing a focused analysis of those who underwent both NPI and RS (n = 329), neither biomarker predicted DFS or OS. Using Kaplan Meier analyses, NPI category predicted DFS (P = 0.008) and (P = 0.026) OS. Conversely, 21-gene RS group failed to predict DFS (P = 0.187) and OS (P = 0.296). CONCLUSION: In our focused analysis, neither NPI nor RS predicted survival outcomes. However, in the entire series, NPI independently predicted both DFS and OS. On the 40th anniversary since its derivation, NPI continues to provide accurate prognostication in breast cancer, outperforming RS in the current study.

A Novel Surrogate Nomogram Capable of Predicting OncotypeDX Recurrence Score©.

Background: OncotypeDX Recurrence Score© (RS) is a commercially available 21-gene expression assay which estimates prognosis and guides chemoendocrine prescription in early-stage estrogen-receptor positive, human epidermal growth factor receptor-2-negative (ER+/HER2−) breast cancer. Limitations of RS testing include the cost and turnaround time of several weeks. Aim: Our aim is to develop a user-friendly surrogate nomogram capable of predicting RS. Methods: Multivariable linear regression analyses were performed to determine predictors of RS and RS > 25. Receiver operating characteristic analysis produced an area under the curve (AUC) for each model, with training and test sets were composed of 70.3% (n = 315) and 29.7% (n = 133). A dynamic, user-friendly nomogram was built to predict RS using R (version 4.0.3). Results: 448 consecutive patients who underwent RS testing were included (median age: 58 years). Using multivariable regression analyses, postmenopausal status (ß-Coefficient: 0.25, 95% confidence intervals (CIs): 0.03−0.48, p = 0.028), grade 3 disease (ß-Coefficient: 0.28, 95% CIs: 0.03−0.52, p = 0.026), and estrogen receptor (ER) score (ß-Coefficient: −0.14, 95% CIs: −0.22−−0.06, p = 0.001) all independently predicted RS, with AUC of 0.719. Using multivariable regression analyses, grade 3 disease (odds ratio (OR): 5.67, 95% CIs: 1.32−40.00, p = 0.037), decreased ER score (OR: 1.33, 95% CIs: 1.02−1.66, p = 0.050) and decreased progesterone receptor score (OR: 1.16, 95% CIs: 1.06−1.25, p = 0.002) all independently predicted RS > 25, with AUC of 0.740 for the static and dynamic online nomogram model. Conclusions: This study designed and validated an online user-friendly nomogram from routinely available clinicopathological parameters capable of predicting outcomes of the 21-gene RS expression assay.

Clinicopathological response to neoadjuvant therapies and pathological complete response as a biomarker of survival in human epidermal growth factor receptor-2 enriched breast cancer - A retrospective cohort study.

BACKGROUND: Human epidermal growth factor receptor-2 (HER2) is overexpressed in 20-25% of breast cancers. Complete eradication of disease following neoadjuvant therapies and chemotherapy has been referred to as pathological complete response (pCR). AIMS: To determine clinicopathological predictors of pCR to neoadjuvant therapies and to evaluate pCR as a surrogate to enhanced survival. METHODS: Consecutive female patients with HER2 positive (HER+) breast cancer managed surgically in a single institution between 2005 and 2015 were included. Descriptive statistics and binary logistic regression were used to determine predictors of pCR. Appraisal of pCR as a predictor of survival was performed using Kaplan-Meier curves and Cox regression analysis. RESULTS: 451 patients were included with a mean age of 56.6 ± 13.4 years (range 23-95). Disease-free (DFS) and overall survival (OS) was 82.3% (371/451) and 82.6% (376/451) respectively with a median follow-up of 108.0 months (range 3-184.0). 118 were treated in the neoadjuvant setting (26.2%): tumour size <50 mm (Odds Ratio (OR): 12.156, P = 0.023) and progesterone receptor negativity (OR: 2.762, P = 0.008) independently predicted breast pCR, while ductal carcinoma (OR: 3.203, P = 0.030) and grade 3 disease (OR: 2.788, P = 0.018) predicted axillary pCR. Both breast and axillary pCR predicted enhanced DFS (Hazard Ratio (HR): 0.470 & HR: 0.449) and OS (HR: 0.383 & HR: 0.307). Axillary pCR independently predicted improved OS (HR: 0.326). CONCLUSION: pCR is sensitive biomarker and surrogate to survival outcomes in HER2+ breast cancer. Patients likely to achieve pCR may be predicted from traditional clinicopathological characteristics and molecular parameters.

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.

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.

The role of liver resection in patients with metastatic breast cancer: a systematic review examining the survival impact.

INTRODUCTION: Approximately 10% of breast cancer patients will present with solid organ metastases, while up to 30% will develop metastatic disease during their treatment course. Liver metastases are usually treated with systemic chemotherapy. Although colorectal liver metastases are routinely resected, this is not yet the standard of care for breast cancer-related liver metastases. This review examines the evidence for resection of breast cancer-related liver metastases. METHODS: A systematic review identified 25 articles for inclusion, 12 papers concerning patients with isolated liver metastases, and 13 papers concerning patients with extrahepatic metastases. Data from 1080 patients were included. RESULTS: Two hundred eighty patients underwent hepatic resections for breast cancer-associated metastases with no extrahepatic metastases. Reported 5-year survival ranged from 24.6 to 78%. Median overall survival ranged from 29.5 to 116 months. For patients with oligometastatic disease undergoing resection, 5-year survival ranged from 21 to 57%, with median overall survival ranging from 32 to 58 months. Reported 30-day morbidity ranged from 14 to 42% for isolated and multiple metastases. CONCLUSION: Hepatic resection can be considered in the management of breast cancer patients with isolated liver metastases as well as those with oligometastatic disease.

Science or popular media: What drives breast cancer online activity?

Google Trends is reflective of international awareness. Since its launch in 2004, there have been several landmark publications, international awareness campaigns, and mainstream-media events that involve breast cancer. The aim of this study was to assess the impact of landmark academic publications vs mainstream-media announcements in driving online breast cancer activity via Google Trends. Ten breast cancer-related themes or landmark publications (five academic publications and five media-related events) were used to compare the impact of online search activity. This activity was determined by retrospectively analyzing Google Trends data over a 12-year period (2004-2016) and calculating the relative search volume. Breast cancer searches showed a slight decrease in the twelve-year period. Since 2004, eight of top 10 Breast Cancer searches were in October. This coincides with breast cancer awareness month. The major five academic publications were all published in the New England Journal of Medicine or the Lancet. Interestingly, only one publication (Tailor-X trial) made the top 10 spikes in relative search volume. Academic publications as expected generate lower rates of public awareness and Internet searching. However, if academic publications are coupled with media releases, there is considerable potential for achieving increased public awareness.

Thoracic paravertebral blockade in breast surgery: Is pneumothorax an appreciable concern? A review of over 1000 cases.

There has been a substantial increase in ambulatory day-case breast surgery in recent decades. This has been largely due to improvements in anesthetic procedures and pre-emptive analgesia. Thoracic paravertebral blockade (TPVB) is increasing in popularity, though concerns over iatrogenic injury remain, especially pneumothorax. The purpose of this study was to conduct a review of the incidence of pneumothorax following TPVB prior to breast surgery. Data from of a consecutive series of patients having TPVB prior to breast surgery between 2009 and 2014 were reviewed. TPVB were used prior to unilateral and bilateral procedures. Medical records were retrospectively assessed for any complication including pleural punctures, pneumothorax, hypotension, bradycardia as well as signs and symptoms of local anesthetic toxicity. 1152 patients underwent a total of 1322 TPVB injections (982 unilateral and 340 bilateral). Clinically significant hypotension and/or bradycardia occurred in 26 patients (2.2%). Two patients (0.17%) had a suspected toxicity from the local anesthetic. Incidence of pleural puncture was 0.6% (n=9) and pneumothorax 0.26% (n=3). All pneumothoraxes were managed conservatively. There was no statistical difference in complication rates in those that had unilateral vs bilateral TPVB or those that had ultrasound guidance (P=.09). Good pre-emptive analgesia is pertinent to prevent acute postoperative pain. TPVB have been shown to be successful in reducing rescue analgesia. This study shows TPVB is a well-tolerated procedure, with a low associated incidence of iatrogenic injury and complication.

Turbulent tackle: a novel surgical approach to a rugby-related jejunal perforation.

Viscus perforation in the context of blunt-force abdominal trauma is a rarity. Within a sporting context, it is especially rare. However, the increasing physicality observed in rugby union, both in the amateur and professional setting, has resulted in a higher rate of serious injury. We report a novel laparoscopic surgical approach to the management of a traumatic jejunal perforation sustained on the playing field in a previously fit and healthy 28-year-old.

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.

A rare case of Fournier's Gangrene.

We report a rare case that highlights acute pancreatitis as the protagonist of Fournier's Gangrene. This patient was treated with a radical debridement of his perineum at presentation and subsequently reconstructed with split thickness skin grafting. This is an unusual aetiology of necrotizing fasciitis with only one other case reported in the literature. This serves to emphasize to physicians that acute pancreatitis is a potential source when investigating and treating patients with Fournier's Gangrene.

Exploring circulating micro-RNA in the neoadjuvant treatment of breast cancer.

Breast cancer is the most frequently diagnosed malignancy amongst females worldwide. In recent years the management of this disease has transformed considerably, including the administration of chemotherapy in the neoadjuvant setting. Aside from increasing rates of breast conserving surgery and enabling surgery via tumour burden reduction, use of chemotherapy in the neoadjuvant setting allows monitoring of in vivo tumour response to chemotherapeutics. Currently, there is no effective means of identifying chemotherapeutic responders from non-responders. Whilst some patients achieve complete pathological response (pCR) to chemotherapy, a good prognostic index, a proportion of patients derive little or no benefit, being exposed to the deleterious effects of systemic treatment without any knowledge of whether they will receive benefit. The identification of predictive and prognostic biomarkers could confer multiple benefits in this setting, specifically the individualization of breast cancer management and more effective administration of chemotherapeutics. In addition, biomarkers could potentially expedite the identification of novel chemotherapeutic agents or increase their efficacy. Micro-RNAs (miRNAs) are small non-coding RNA molecules. With their tissue-specific expression, correlation with clinicopathological prognostic indices and known dysregulation in breast cancer, miRNAs have quickly become an important avenue in the search for novel breast cancer biomarkers. We provide a brief history of breast cancer chemotherapeutics and explore the emerging field of circulating (blood-borne) miRNAs as breast cancer biomarkers for the neoadjuvant treatment of breast cancer. Established molecular markers of breast cancer are outlined, while the potential role of circulating miRNAs as chemotherapeutic response predictors, prognosticators or potential therapeutic targets is discussed.

A Circulating MicroRNA Signature as a Biomarker for Prostate Cancer in a High Risk Group.

INTRODUCTION: Mi(cro)RNAs are small non-coding RNAs whose differential expression in tissue has been implicated in the development and progression of many malignancies, including prostate cancer. The discovery of miRNAs in the blood of patients with a variety of malignancies makes them an ideal, novel biomarker for prostate cancer diagnosis. The aim of this study was to identify a unique expression profile of circulating miRNAs in patients with prostate cancer attending a rapid access prostate assessment clinic. METHODS: To conduct this study blood and tissue samples were collected from 102 patients (75 with biopsy confirmed cancer and 27 benign samples) following ethical approval and informed consent. These patients were attending a prostate assessment clinic. Samples were reverse-transcribed using stem-loop primers and expression levels of each of 12 candidate miRNAs were determined using real-time quantitative polymerase chain reaction. miRNA expression levels were then correlated with clinicopathological data and subsequently analysed using qBasePlus software and Minitab. RESULTS: Circulating miRNAs were detected and quantified in all subjects. The analysis of miRNA mean expression levels revealed that four miRNAs were significantly dysregulated, including let-7a (p = 0.005) which has known tumour suppressor characteristics, along with miR-141 (p = 0.01) which has oncogenic characteristics. In 20 patients undergoing a radical retropubic-prostatectomy, the expression levels of miR-141 returned to normal at day 10 post-operatively. A panel of four miRNAs could be used in combination to detect prostate cancer with an area under the curve (AUC) of 0.783 and a PPV of 80%. CONCLUSION: These findings identify a unique expression profile of miRNA detectable in the blood of prostate cancer patients. This confirms their use as a novel, diagnostic biomarker for prostate cancer.

Estrogen withdrawal, increased breast cancer risk and the KRAS-variant.

The KRAS-variant is a biologically functional, microRNA binding site variant, which predicts increased cancer risk especially for women. Because external exposures, such as chemotherapy, differentially impact the effect of this mutation, we evaluated the association of estrogen exposures, breast cancer (BC) risk and tumor biology in women with the KRAS-variant. Women with BC (n = 1712), the subset with the KRAS-variant (n = 286) and KRAS-variant unaffected controls (n = 80) were evaluated, and hormonal exposures, KRAS-variant status, and pathology were compared. The impact of estrogen withdrawal on transformation of isogenic normal breast cell lines with or without the KRAS-variant was studied. Finally, the association and presentation characteristics of the KRAS-variant and multiple primary breast cancer (MPBC) were evaluated. KRAS-variant BC patients were more likely to have ovarian removal pre-BC diagnosis than non-variant BC patients (p = 0.033). In addition, KRAS-variant BC patients also appeared to have a lower estrogen state than KRAS-variant unaffected controls, with a lower BMI (P < 0.001). Finally, hormone replacement therapy (HRT) discontinuation in KRAS-variant patients was associated with a diagnosis of triple negative BC (P < 0.001). Biologically confirming our clinical findings, acute estrogen withdrawal led to oncogenic transformation in KRAS-variant positive isogenic cell lines. Finally, KRAS-variant BC patients had greater than an 11-fold increased risk of presenting with MPBC compared to non-variant patients (45.39% vs 6.78%, OR 11.44 [3.42-37.87], P < 0.001). Thus, estrogen withdrawal and a low estrogen state appear to increase BC risk and to predict aggressive tumor biology in women with the KRAS-variant, who are also significantly more likely to present with multiple primary breast cancer.

Evolution of a research field-a micro (RNA) example.

Background. Every new scientific field can be traced back to a single, seminal publication. Therefore, a bibliometric analysis can yield significant insights into the history and potential future of a research field. This year marks 21 years since that first ground-breaking microRNA (miRNA) publication. Here, we make the case that the miRNA field is mature, utilising bibliometrics. Methods. Utilising the Web of Science™ (WoS) database publication and citation information, we charted the history of miRNA-related publications, describing and dissecting contributions by publication type (plus category, pay-per-view or open access), journal (highlighting dominant journals), by country, citations and languages. Results. We found that the United States of America (USA) publishes the most miRNA papers, followed by China and Germany. Significantly, publications attributed to the USA also receive the most citations per publication, followed by a close grouping of England, Germany and France. We also describe the relevance and acceptance of the miRNA field to different research areas, through its uptake in areas from oncology to plant sciences. Exploring the recent momentous change in publishing, we find that although pay-per view articles vastly out-number open-access articles, the citation rate of pay-per-view articles is currently less than double that of open-access. Conclusions. We believe the trends described here represent the typical evolution of a research field. By analysing publications, citations and distribution patterns, key moments in the evolution of this research area are recognised, indicating the maturation of the miRNA field and providing guidance for future research endeavours.

The oncologic safety and practicality of breast conservation surgery in large breast tumors 5 centimeters or more.

BACKGROUND: Surgery remains a therapeutic strategy for women with breast cancer, and long-term outcomes for breast conservation surgery (BCS) and radiotherapy are equivalent to those for mastectomy. To date, there are few published data assessing the oncologic safety and practicality of BCS in women with large breast cancers ≥ 5 cm. The current study compares survival outcomes for women with breast cancer ≥ 5 cm undergoing BCS or mastectomy. METHODS: All women undergoing surgery for breast cancer ≥ 5 cm between January 2004 and December 2011 were included in this study. Kaplan-Meier survival curves statistically compared the overall survival (OS), disease-free survival (DFS), and local recurrence-free survival (LRFS) in the BCS and mastectomy groups. Statistical analysis involved chi-square analysis and t test. The mean length of follow-up was 55.25 months (range, 6-115 months). RESULTS: A total of 217 women had surgery for tumors ≥ 5 cm (BCS in 51, mastectomy in 166). There was no statistical difference in the OS, DFS, and LRFS between groups (P = .439; 95% confidence interval, 0.114-0.347). The re-excision rate of women undergoing BCS was 45.1%, with 65.2% of women undergoing a completion mastectomy. Extensive ductal carcinoma in situ represented the only significant risk factor associated with inadequate margins (P = .021). Larger tumor size was associated with a greater risk of local recurrence (P = .039). CONCLUSIONS: This study is one of the largest studies to date to report BCS + radiotherapy as a safe oncologic treatment option for women with large breast cancers. However, the higher re-excision rate advocates a need to investigate ways to improve patient selection.

A genetic variant at 12p11 significantly modifies breast cancer risk in a genetically homogenous island population.

Genome-wide association studies have identified novel breast cancer susceptibility loci at 12q24 (rs1292011), 12p11 (rs10771399) and 21q21 (rs2823093). The aim of our study was to investigate the prevalence of variants at these three loci in an Irish sample, and to examine the association between these variants and breast cancer in this cohort. DNA was extracted from the blood or buccal swabs of Irish patients with breast cancer (cases), as well as from healthy Irish female controls. Genotyping was performed for each target using a Taqman-based platform. Data were analysed using IBM Statistical Package for the Social Sciences version 22. Genotyping was performed on samples from 1,267 patients with breast cancer and 841 cancer-free controls. The per-allele odds ratio associated with the minor allele at 12p11 was found to be 0.67 (0.54-0.81, p < 0.001). Genotype-specific odds ratios showed an allele dosage effect with odds ratio of 0.76 (0.6-0.95) for heterozygotes, and 0.23 (0.1-0.51) for rare homozygotes. Minor allele frequencies of the variants at 12q24 and 21q21 did not differ significantly between cases or controls. All three investigated variants were identified in the Irish population. The polymorphism rs10771399 was strongly associated with breast cancer risk in this cohort, and was shown to be associated with reduced odds ratio for all molecular subtypes.

Is there a role for locoregional surgery in stage IV breast cancer?

Current guidelines do not recommend locoregional surgery for Stage IV breast cancer at presentation despite some studies suggesting a survival benefit. We aimed to assess outcomes in patients with Stage IV breast cancer who underwent surgery. In a cohort study of all Stage IV breast cancers diagnosed at our tertiary-referral specialist centre between 2006 and 2012, we assessed patient survival in the context of demographics, histopathology, metastatic burden, and type of surgery performed. One hundred and nine patients were included; 52 underwent surgery. Patients in the surgery group had longer 5-year-survival (p = 0.003). Survival was also significantly longer in those with just one site of metastatic disease (p < 0.001). Patients with axillary cytology positive for regional metastases were less likely to proceed to surgery. Locoregional surgery does confer a survival advantage in Stage IV breast cancer. Assessment of preoperative axillary cytology may preclude some patients from proceeding to potentially beneficial locoregional surgery.