Nodal positivity in patients with clinically and radiologically node-negative breast cancer treated with neoadjuvant chemotherapy: multicentre collaborative study.

BACKGROUND: The necessity of performing a sentinel lymph node biopsy in patients with clinically and radiologically node-negative breast cancer after neoadjuvant chemotherapy has been questioned. The aim of this study was to determine the rate of nodal positivity in these patients and to identify clinicopathological features associated with lymph node metastasis after neoadjuvant chemotherapy (ypN+). METHODS: A retrospective multicentre study was performed. Patients with cT1-3 cN0 breast cancer who underwent sentinel lymph node biopsy after neoadjuvant chemotherapy between 2016 and 2021 were included. Negative nodal status was defined as the absence of palpable lymph nodes, and the absence of suspicious nodes on axillary ultrasonography, or the absence of tumour cells on axillary nodal fine needle aspiration or core biopsy. RESULTS: A total of 371 patients were analysed. Overall, 47 patients (12.7%) had a positive sentinel lymph node biopsy. Nodal positivity was identified in 22 patients (29.0%) with hormone receptor+/human epidermal growth factor receptor 2- tumours, 12 patients (13.8%) with hormone receptor+/human epidermal growth factor receptor 2+ tumours, 3 patients (5.6%) with hormone receptor-/human epidermal growth factor receptor 2+ tumours, and 10 patients (6.5%) with triple-negative breast cancer. Multivariable logistic regression analysis showed that multicentric disease was associated with a higher likelihood of ypN+ (OR 2.66, 95% c.i. 1.18 to 6.01; P = 0.018), whilst a radiological complete response in the breast was associated with a reduced likelihood of ypN+ (OR 0.10, 95% c.i. 0.02 to 0.42; P = 0.002), regardless of molecular subtype. Only 3% of patients who had a radiological complete response in the breast were ypN+. The majority of patients (85%) with a positive sentinel node proceeded to axillary lymph node dissection and 93% had N1 disease. CONCLUSION: The rate of sentinel lymph node positivity in patients who achieve a radiological complete response in the breast is exceptionally low for all molecular subtypes.

Perioperative cell-free DNA trends predict recurrence of non-metastatic colorectal cancer significantly earlier than CEA trends over the first 2 years post-operatively in stage II and stage III colon cancer.

PURPOSE: We aimed to compare the diagnostic accuracy of perioperative ΔcfDNA to ΔCEA (over the first 2 years post-operatively) for identifying disease recurrence in colon cancer. METHODS: Patients presenting for elective resection for colon cancer with curative intent were screened for inclusion. Perioperative cfDNA levels were measured at seven different times points(pre-operative and post-operative at 3 h, 6 h, 24 h, 48 h, POD3 and POD5). CEA levels were measured on the same patients up to 2 years post-operatively. Change in trend (Δ) was defined as the ß coefficient using a logistic regression model. Statistical analysis was performed using SPSS, version 23. RESULTS: Longitudinal data on twenty-two patients were analysed (n = 16 male, n = 6 female) for a median of 29 months (IQR 23 months) during which time three patients developed (distant) recurrence. Perioperative ΔcfDNA at 48Hrs, POD3 and POD5 were significantly associated with early recurrence. ΔCEA was significantly associated with early recurrence at 6 months, 1 year and 2 years post-operatively, only when disease recurrence was macroscopically established. ΔcfDNA was associated with an area under the curve (AUC) of 0.947 (95% CI 0.88-1.0, p < 0.001) and ΔCEA was associated with an AUC of 0.9382 (95%CI 0.88-0.99, p < 0.0001). This translated into a specificity of 97% (95%CI 86.51-99.87%) for ΔcfDNA and 77.5% sensitivity (95%CI 62.5-87.7%) in the immediate perioperative period and an 88.9% specificity (95%CI 56.5-99.4%) and 76.5% sensitivity (95%CI 63.24-86%) for ΔCEA over the first 2 years post-operatively. CONCLUSIONS: In this pilot study, following curative resection for colon cancer changing trends in perioperative cfDNA (ΔcfDNA) identify those at risk of recurrent disease before recurrence develops which is at least 6 months earlier than CEA changes (ΔCEA) which are only observed when recurrence is established.

Determining the need for a breast cancer awareness educational intervention for women with mild/moderate levels of intellectual disability: A qualitative descriptive study.

OBJECTIVE: Following a review of the existing body of literature, this study aimed to explore the need for a breast cancer awareness intervention specifically targeted at women with mild/moderate levels of intellectual disability (ID) and provide perspectives on the preferred processes and content underpinning an intervention. METHODS: A qualitative, descriptive design using semi-structured, individual (n = 5) and focus group (n = 5) interviews were used to engage with a non-probability, purposive sample of key stakeholders (n = 25) including women with mild/moderate levels of ID, caregivers and healthcare professionals. Data were analysed using qualitative content analysis. RESULTS: Findings highlighted that an educational intervention should focus on breast awareness as opposed to breast cancer awareness. Additionally, findings identified that a combined breast awareness and healthy living intervention could be effective. However, the intervention needs to have a multimodal, hands-on, person-centred approach to learning which is underpinned by theory. Furthermore, integrating the caregivers and healthcare professionals into the intervention is recommended. CONCLUSION: Findings from this study provide a foundation for developing and implementing a theoretically underpinned, multimodal, breast awareness and healthy living educational intervention for women with mild/moderate levels of ID.

The LOCalizer Radiofrequency Identification System: An Effective New Technology for Localizing Non-Palpable Breast Lesions for Surgery.

Background. Breast screening has decreased morbidity and mortality due to detection of early, non-palpable breast cancers. One of the challenges of performing breast-conserving surgery on non-palpable breast tumours is accurate localization of the cancer. We aimed to perform a feasibility study to examine the outcomes associated with the introduction of a novel radiofrequency identification system (RFID) called LOCalizer as an alternative to traditional wire-guided localization. Methods. Data were prospectively collected on all patients undergoing breast-conserving surgery using the LOCalizer RFID system in a regional cancer centre between July 2019 and March 2020. Patients had a RFID tag placed preoperatively and underwent surgical removal of the tag with the index lesion guided by a handheld LOCalizer probe. The primary aim was successful placement and retrieval of the RFID tag. Re-excision rates, specimen size, specimen weight, cancer subtype and complication rate were all recorded. Results. Sixty-nine patients aged between 50 and 69 years had a LOCalizer tag inserted between July 2019 and March 2020. Of these, 6 (8.7%) were diagnostic and 63 (91.3%) were therapeutic. There was no migration of RFID tags, and all tags were retrieved with the index lesion. The overall re-excision of margin rate was 17.4% (12/69). All re-excision of margins was due to positive radial margins. The overall complication rate was 1.4% with one grade 1 Clavien-Dindo morbidity. Conclusion. The LOCalizer RFID is an effective and safe wire-free localization method for non-palpable breast lesions.

Defining breast cancer awareness and identifying barriers to breast cancer awareness for women with an intellectual disability: A review of the literature.

INTRODUCTION: Incidence rates for developing breast cancer are similar for women regardless of intellectual ability. However, women with an intellectual disability present with advanced breast cancers, which often have a poor prognosis. METHOD: A structured narrative review of the literature was performed to explore the concepts of breast awareness and breast cancer awareness and subsequently, identify barriers to breast cancer awareness encountered by women with an intellectual disability. RESULTS: A total of 22 studies involving people with varying levels of intellectual disability informed this review. The barriers to breast cancer awareness encountered by women with an intellectual disability include: lack of their understanding, the role of the carer and literacy issues. CONCLUSION: Identifying the barriers to breast cancer awareness for women with an intellectual disability will help to facilitate breast cancer awareness which has the potential to result in better long-term outcomes through an early diagnosis of breast cancer.

The clinicomolecular landscape of de novo versus relapsed stage IV metastatic breast cancer.

BACKGROUND: de novo metastatic breast cancer (dnMBC) is responsible for 6-10% of breast cancer presentations with increasing incidence and has remained resistant to detection by mammography screening. Recent publications hypothesized that in addition to poor screening uptake, the presentation of dnMBC may be due to its unfavourable biology which remains unknown at the molecular level. Here we investigated the tumour biology of dnMBC in the form of clinicopathology, genomic alterations and differential gene expression to create a comparative landscape of de novo versus relapsed metastatic breast cancer (rMBC). Additionally, to address the current screening limitations, we conducted a preliminary biomarker investigation for early dnMBC detection. METHODS: In this retrospective case-control study, gene expression and clinical data were accessed from the Cancer Genome Atlas (TCGA) for primary tumours of treatment-naïve patients with dnMBC (n = 17), rMBC (n = 49), and normal tissue (n = 113). The clinical and histological data were assessed categorically using Fisher's Exact-Test for significance (p < .05), or continuously using the Mann-Whitney Test (p < .05) where appropriate. The differential gene expression analysis was performed using EdgeR's negative binomial distribution model with a false discovery rate (FDR) <0.05. The resulting gene list was analysed manually for roles in metastasis as well as ontologically using STRING-DB with FDR <0.05. RESULTS: dnMBCs showed improved median survival vs rMBC (36 vs. 12 months). dnMBCs were more likely to be hormone receptor positive, less likely to be triple negative with lower histological lymphocytic infiltrate. In terms of genome alterations, dnMBCs had 4-fold increased PTEN mutations and poor survival with ABL2 and GATA3 alterations. Expression-wise, dnMBCs down-regulated TNFa, IL-17 signalling, and chemotaxis, while up-regulating steroid biosynthesis, cell migration, and cell adhesion. Biomarker analysis detected pre-existing and novel breast cancer biomarkers. CONCLUSION: The comparative tumour landscape revealed significant clinical, pathological and molecular differences between dnMBC and rMBC, indicating that dnMBC may be a separate biological entity to rMBC at the primary level with differing paths to metastasis. Additionally, we provided a list of potential serum biomarkers that may be useful in detecting dnMBC in its pre-metastatic window if such a window exists.

The Efficacy of Prophylactic Negative Pressure Wound Therapy for Closed Incisions in Breast Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Negative pressure wound therapy (NPWT) is a promising advance in the management of closed surgical incisions. NPWT application induces several effects locally within the wound including reduced lateral tension and improving lymphatic drainage. As a result, NPWT may improve wound healing and reduce surgical site complications. We aim to evaluate the efficacy of prophylactic application of NPWT in preventing surgical site complications for closed incisions in breast surgery. METHODS: This systematic review was reported according to PRISMA guidelines. The protocol was published in PROSPERO (CRD42018114625). Medline, Embase, CINAHL and Cochrane Library databases were searched for studies which compare the efficacy of NPWT versus non-NPWT dressings for closed incisions in breast surgery. Specific outcomes of interest were total wound complications, surgical site infection (SSI), seroma, haematoma, wound dehiscence and necrosis. RESULTS: Seven studies (1500 breast incisions in 904 patients) met the inclusion criteria. NPWT was associated with a significantly lower rate of total wound complications [odds ratio (OR) 0.36; 95% CI 0.19-069; P = 0.002], SSI (OR 0.45; 95% CI 0.24-0.86; P = 0.015), seroma (OR 0.28; 95% CI 0.13-0.59; P = 0.001), wound dehiscence (OR 0.49; 95% CI 0.32-0.72; P < 0.001) and wound necrosis (OR 0.38; 95% CI 0.19-0.78; P = 0.008). There was no significant difference in haematoma rate (OR 0.8; 95% CI 0.19-3.2; P = 0.75). Statistically significant heterogeneity existed for total wound complications, but no other outcomes. CONCLUSION: Compared with conventional non-NPWT dressings, prophylactic application of NPWT is associated with significantly fewer surgical site complications including SSI, seroma, wound dehiscence and wound necrosis for closed breast incisions.

Assessing the accuracy of conventional gadolinium-enhanced breast MRI in measuring the nodal response to neoadjuvant chemotherapy (NAC) in breast cancer.

Management of the axilla in the era of neoadjuvant chemotherapy for breast cancer is evolving. The aim of this study is to determine if conventional gadolinium-enhanced breast MRI can aid in evaluation of the response to neoadjuvant chemotherapy in the axilla. A retrospective review of a prospectively maintained database of patients undergoing neoadjuvant chemotherapy for breast cancer was performed. Pre and post-neoadjuvant chemotherapy MRI reports for node-positive patients were examined in conjunction with demographic data, treatment type, and final histopathology reports. One-hundred and fourteen patients with breast cancer undergoing neoadjuvant chemotherapy were included in the study. The sensitivity of magnetic resonance imaging in detecting nodal response post-neoadjuvant chemotherapy was 33.93% and the specificity was 82.76%. Magnetic resonance imaging had a positive predictive value of 65.52% and a negative predictive value of 56.47%. MRI was found to be most specific in the detection of triple-negative cancer response. Specificity was 100% in this group and sensitivity was 75%. Magnetic resonance imaging has a relatively high specificity in detecting nodal response post-neoadjuvant chemotherapy but has a low sensitivity. Alone it cannot be relied upon to identify active axillary malignancy post-neoadjuvant chemotherapy. However, given its increased specificity among certain subgroups, it may have a role in super-selecting patients suitable for sentinel lymph node biopsy post-neoadjuvant chemotherapy.

Is excision biopsy of fibroadenomas based solely on size criteria warranted?

Fibroadenomas (FA) are the most common benign tumor in the female breast. Most are managed conservatively provided there is clinical, radiologic, and pathologic concordance. However, surgical excision is typically recommended for cellular fibroepithelial lesions or those lesions with clinical, radiologic, or pathologic features concerning for phyllodes tumor (PT). Some studies have suggested surgical excision in all FA >30 mm to reduce core needle biopsy (CNB) sampling errors. The aim of our study was to evaluate, in the absence of any other concerning clinicopathologic features, whether surgical excision of FA was warranted based on size criteria alone. Cork University Hospital is a large academic center in Southern Ireland. Its breast cancer center provides both a screening and symptomatic service and diagnoses approximately 600 cancers per year. The breast histopathological data base was reviewed for all CNBs from January 1, 2010, to June 30, 2015, with a diagnosis of FA that went on to have excision at our institution. We excluded all cellular fibroepithelial lesions and those cases with co-existent lobular neoplasia, ductal carcinoma in situ, invasive carcinoma, atypical ductal hyperplasia, or lesions which would require excision in their own right. Cases in which the radiologic targeted mass was discordant with a diagnosis of FA were also excluded. Patient demographics and preoperative radiologic size and the radiologic target were recorded in each case. All radiology was reviewed by a breast radiologist prior to inclusion in the study, and there was histologic radiologic concordance with a diagnosis of FA in all cases. A total of 12,109 consecutive radiologically guided CNB were performed January 2010-June 2015; 3438 with a diagnosis of FA were identified of which 290 cases went on to have surgical excision. Of those 290 cases; 98.28% (n = 285) were confirmed as FA on excision. The remaining 1.72% (n = 5) had atypical features-FA with LCIS (n = 1), benign PT (n = 3), and invasive ductal carcinoma (n = 1). Our study suggests that, excision based solely on size is not warranted in clinical and radiologically concordant cases with a diagnosis of FA on CNB.

Printed freeform lens arrays on multi-core fibers for highly efficient coupling in astrophotonic systems.

Coupling of light into multi-core fibers (MCF) for spatially resolved spectroscopy is of great importance to astronomical instrumentation. To achieve high coupling efficiencies along with fill-fractions close to unity, micro-optical elements are required to concentrate the incoming light to the individual cores of the MCF. In this paper we demonstrate facet-attached lens arrays (LA) fabricated by two-photon polymerization. The LA provide close to 100% fill-fraction along with efficiencies of up to 73% (down to 1.4 dB loss) for coupling of light from free space into an MCF core. We show the viability of the concept for astrophotonic applications by integrating an MCF-LA assembly in an adaptive-optics test bed and by assessing its performance as a tip/tilt sensor.

Interventions for raising breast cancer awareness in women.

BACKGROUND: Breast cancer continues to be the most commonly diagnosed cancer in women globally. Early detection, diagnosis and treatment of breast cancer are key to better outcomes. Since many women will discover a breast cancer symptom themselves, it is important that they are breast cancer aware i.e. have the knowledge, skills and confidence to detect breast changes and present promptly to a healthcare professional. OBJECTIVES: To assess the effectiveness of interventions for raising breast cancer awareness in women. SEARCH METHODS: We searched the Cochrane Breast Cancer Group's Specialised Register (searched 25 January 2016), Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 12) in the Cochrane Library (searched 27 January 2016), MEDLINE OvidSP (2008 to 27 January 2016), Embase (Embase.com, 2008 to 27 January 2016), the World Health Organization's International Clinical Trials Registry Platform (ICTRP) search portal and ClinicalTrials.gov (searched 27 Feburary 2016). We also searched the reference lists of identified articles and reviews and the grey literature for conference proceedings and published abstracts. No language restriction was applied. SELECTION CRITERIA: Randomised controlled trials (RCTs) focusing on interventions for raising women's breast cancer awareness i.e. knowledge of potential breast cancer symptoms/changes and the confidence to look at and feel their breasts, using any means of delivery, i.e. one-to-one/group/mass media campaign(s). DATA COLLECTION AND ANALYSIS: Two authors selected studies, independently extracted data and assessed risk of bias. We reported the odds ratio (OR) and 95% confidence intervals (CIs) for dichotomous outcomes and mean difference (MD) and standard deviation (SD) for continuous outcomes. Since it was not possible to combine data from included studies due to their heterogeneity, we present a narrative synthesis. We assessed the quality of evidence using GRADE methods. MAIN RESULTS: We included two RCTs involving 997 women: one RCT (867 women) randomised women to receive either a written booklet and usual care (intervention group 1), a written booklet and usual care plus a verbal interaction with a radiographer or research psychologist (intervention group 2) or usual care (control group); and the second RCT (130 women) randomised women to either an educational programme (three sessions of 60 to 90 minutes) or no intervention (control group). Knowledge of breast cancer symptomsIn the first study, knowledge of non-lump symptoms increased in intervention group 1 compared to the control group at two years postintervention, but not significantly (OR 1.1, 95% CI 0.7 to 1.6; P = 0.66; 449 women; moderate-quality evidence). Similarly, at two years postintervention, knowledge of symptoms increased in the intervention group 2 compared to the control group but not significantly (OR 1.4, 95% CI 0.9 to 2.1; P = 0.11; 434 women; moderate-quality evidence). In the second study, women's awareness of breast cancer symptoms had increased one month post intervention in the educational group (MD 3.45, SD 5.11; 65 women; low-quality evidence) compared to the control group (MD -0.68, SD 5.93; 65 women; P < 0.001), where there was a decrease in awareness. Knowledge of age-related riskIn the first study, women's knowledge of age-related risk of breast cancer increased, but not significantly, in intervention group 1 compared to control at two years postintervention (OR 1.8; 95% CI 0.9 to 3.5; P < 0.08; 447 women; moderate-quality evidence). Women's knowledge of risk increased significantly in intervention group 2 compared to control at two years postintervention (OR 4.8, 95% CI 2.6 to 9.0; P < 0.001; 431 women; moderate-quality evidence). In the second study, women's perceived susceptibility (how at risk they considered themselves) to breast cancer had increased significantly one month post intervention in the educational group (MD 1.31, SD 3.57; 65 women; low-quality evidence) compared to the control group (MD -0.55, SD 3.31; 65 women; P = 0.005), where a decrease in perceived susceptibility was noted. Frequency of Breast CheckingIn the first study, no significant change was noted for intervention group 1 compared to control at two years postintervention (OR 1.1, 95% CI 0.8 to 1.6; P = 0.54; 457 women; moderate-quality evidence). Monthly breast checking increased, but not significantly, in intervention group 2 compared to control at two years postintervention (OR 1.3, 95% CI 0.9 to 1.9; P = 0.14; 445 women; moderate-quality evidence). In the second study, women's breast cancer preventive behaviours increased significantly one month post intervention in the educational group (MD 1.21, SD 2.54; 65 women; low-quality evidence) compared to the control group (MD 0.15, SD 2.94; 65 women; P < 0.045). Breast Cancer AwarenessWomen's overall breast cancer awareness did not change in intervention group 1 compared to control at two years postintervention (OR 1.8, 95% CI 0.6 to 5.30; P = 0.32; 435 women; moderate-quality evidence) while overall awareness increased in the intervention group 2 compared to control at two years postintervention (OR 8.1, 95% CI 2.7 to 25.0; P < 0.001; 420 women; moderate-quality evidence). In the second study, there was a significant increase in scores on the Health Belief Model (that included the constructs of awareness and perceived susceptibility) at one month postintervention in the educational group (mean 1.21, SD 2.54; 65 women) compared to the control group (mean 0.15, SD 2.94; 65 women; P = 0.045).Neither study reported outcomes relating to motivation to check their breasts, confidence to seek help, time from breast symptom discovery to presentation to a healthcare professional, intentions to seek help, quality of life, adverse effects of the interventions, stages of breast cancer, survival estimates or breast cancer mortality rates. AUTHORS' CONCLUSIONS: Based on the results of two RCTs, a brief intervention has the potential to increase women's breast cancer awareness. However, findings of this review should be interpreted with caution, as GRADE assessment identified moderate-quality evidence in only one of the two studies reviewed. In addition, the included trials were heterogeneous in terms of the interventions, population studied and outcomes measured. Therefore, current evidence cannot be generalised to the wider context. Further studies including larger samples, validated outcome measures and longitudinal approaches are warranted.

Extended Adjuvant Endocrine Therapy in Breast Cancer: Evidence and Update - A Review.

The optimal duration and treatment strategies involving adjuvant endocrine therapy in early breast cancer remained largely undetermined. As data emerge on the various modalities of treatment in both pre- and postmenopausal groups, debates, and discussions continue. Most studies to date focused on the 5-year duration of treatment consisting of mainly tamoxifen. The Arimidex, Tamoxifen, Alone or in Combination (ATAC) study demonstrated that anastrozole is superior to tamoxifen and has become the mainstream treatment in postmenopausal women with early breast cancer, although the duration was arbitrarily set for 5 years, analogous to tamoxifen treatment. Several clinical trials, however, have emerged to support extended endocrine therapy as it becomes clear that the recurrence risk of breast cancer does not decrease beyond the initial 5 years of treatment. The advent of molecular signatures also plays an important role in the breast cancer profiling, and where available should be incorporated in the overall decision-making. Furthermore, side effects and noncompliance pose another issue in achieving an optimal treatment benefit. The decision-making as regards to extended endocrine treatment should therefore focus not only on the cancer biology alone but also include treatment side effects, assessment of risk of recurrence and patients' preference. In this review, we present an overview of the published studies to date as well as ongoing studies on the topic to better refine the options for adjuvant hormonal therapy.

Transatlantic peer-to-peer learning: an initial feasibility analysis.

INTRODUCTION: Peer-to-peer learning is a well-established learning modality, which has been shown to improve learning outcomes, with positive implications for clinical practice. The purpose of this pilot study was to explore the feasibility of linking students from North America and Europe with a peer-to-peer learning approach. METHODS: Face and content validity studies were completed on the previously designed and validated online repository http://www.pilgrimshospital.com. Four medical students from the University of Toronto, Canada, were paired with four students from University College Cork, Ireland. Each student was invited to upload two pieces of information learned from a senior colleague that day. Each student was asked to review the information uploaded by their partner, editing with references if needed. Quantitative and qualitative evaluations of the e-peer system were conducted. RESULTS: Over the study period, the system recorded a total of 10 079 individual page views. Questionnaires completed by participants demonstrated that 6/8 found the system either "very easy" or "easy" to use, whereas all found that the system promoted evidenced-based and self-directed learning. Structured interviews revealed 3 main themes: The Peer Connection, Trust in Data Veracity, and Aid to Clinical Learning. CONCLUSION: This pilot study demonstrates it is feasible to link students from separate continents in a community of peer-to-peer learning. This is viewed positively by students and enhances evidenced-based learning, and the aspect of peer connectivity was important to participating students. Such an approach encourages peer cooperation and has the potential to disseminate key clinical learning experiences widely.

Association of preoperative and postoperative circulating tumour DNA (ctDNA) with PIK3CA gene mutation with risk of recurrence in patients with non-metastatic breast cancer.

BACKGROUND: Circulating tumour DNA (ctDNA), contains tumour-specific gene mutation in blood circulation and could aid in postoperative risk stratification of non-metastatic breast cancer. In this study, we investigated the feasibility of detecting PIK3CA gene mutations in ctDNA in the preoperative (preop) and postoperative period (postop), and its prognostic significance in patients with breast cancer. METHODS: A cohort of patients with breast cancer undergoing curative surgery with available blood samples preoperatively and postoperatively (Post op) at either Post op time period; week 1-2, week 3-4 or weeks 5-12 were enrolled. PIK3CA gene mutations at exons 9 and 20 were detected in ctDNA with High resolution melting (HRM) PCR and Allele specific fluorescence probe-based PCR. RESULTS: A total of 62 patients (age, median (IQR), 51.50 (45.0-65.0) years), with a median follow-up of 90 months (interquartile range (IQR),60-120 months) were enrolled. In total, 25 (40.3%) and 22 (35%) patients with breast cancer had detectable PIK3CA gene mutations in ctDNA in preoperative and postoperative period, respectively. PIK3CA gene mutations in ctDNA in postoperative period (hazard ratio (H.R: 18.05, p = 0.001) were a negative prognostic factor for recurrencefree survival (RFS) and overall survival (OS) (H.R: 11.9, p = 0.01) in patients with breast cancer. Subgroup analysis of ctDNA indicate that positive ctDNA in both preoperative/postoperative period and post op period only were found to have prognostic effect on RFS and OS (RFS; p < 0.0001, O·S; p = 0.0007). Moreover, ctDNA-based detection preceded clinical detection of recurrence in patients with an average lead time of 12 months (IQR:20-28.5 months) across all the breast cancer subtypes. CONCLUSION: We highlighted the prognostic ability of ctDNA in patients with breast cancer in perioperative period. However, future prospective studies are needed to assess the utility of ctDNA in clinical practice.

The gut microbiota in persistent post-operative pain following breast cancer surgery.

Persistent post-surgical pain (PPSP) is defined as pain which continues after a surgical operation in a significant form for at least three months (and is not related to pre-existing painful conditions). PPSP is a common, under-recognised, and important clinical problem which affects millions of patients worldwide. Preventative measures which are currently available include the selection of a minimally invasive surgical technique and an aggressive multimodal perioperative analgesic regimen. More recently, a role for the gut microbiota in pain modulation has become increasingly apparent. This study aims to investigate any relationship between the gut microbiota and PPSP. A prospective observational study of 68 female adult patients undergoing surgery for management of breast cancer was carried out. Stool samples from 45 of these patients were obtained to analyse the composition of the gut microbiota. Measures of pain and state-trait anxiety were also taken to investigate further dimensions in any relationship between the gut microbiota and PPSP. At 12 weeks postoperatively, 21 patients (51.2%) did not have any pain and 20 patients (48.8%) reported feeling pain that persisted at that time. Analysis of the gut microbiota revealed significantly lower alpha diversity (using three measures) in those patients reporting severe pain at the 60 min post-operative and the 12 weeks post-operative timepoints. A cluster of taxa represented by Bifidobacterium longum, and Faecalibacterium prausnitzii was closely associated with those individuals reporting no pain at 12 weeks postoperatively, while Megamonas hypermegale, Bacteroides pectinophilus, Ruminococcus bromii, and Roseburia hominis clustered relatively closely in the group of patients fulfilling the criteria for persistent post-operative pain. We report for the first time specific associations between the gut microbiota composition and the presence or absence of PPSP. This may provide further insights into mechanisms behind the role of the gut microbiota in the development of PPSP and could inform future treatment strategies.

Increased postoperative complications in bilateral mastectomy patients compared to unilateral mastectomy: an analysis of the NSQIP database.

BACKGROUND: Recent studies indicate that women with unilateral breast cancer are choosing contralateral prophylactic mastectomy (CPM) at an increasing rate. There is limited literature evaluating the postoperative complication rates associated with CPM without breast reconstruction. The objective of this study was to compare postoperative complications in women undergoing unilateral mastectomy (UM) and sentinel lymph node biopsy (SLNB) to those undergoing bilateral mastectomy (BM) and SLNB for the treatment of their breast cancer. METHODS: The American College of Surgeons National Surgery Quality Improvement Program (ACS NSQIP) Participant Use Files between 2007 and 2010 were used to identify women with breast cancer undergoing UM or BM with SLNB. Individual and composite end points of 30-day complications were used to compare both groups by univariate and multivariate analyses. RESULTS: We identified 4,219 breast cancer patients who had a SLNB: 3,722 (88.2 %) had UM and 497 (11.8 %) had BM. The wound complication rate was significantly higher in the BM group versus the UM group, 5.8 % versus 2.9 % [unadjusted odds ratio (OR) 2.1, 95 % confidence interval (CI) 1.3-3.3, P < 0.01]. The overall 30-day complication rate in UM patients was 4.2 % versus 7.6 % in the BM group (unadjusted OR 1.9, 95 % CI 1.3-2.7, P < 0.01). The adjusted OR for overall complications adjusting for important patient characteristics was 1.9 (95 % CI 1.3-2.8, P < 0.01). Independent predictors of overall postoperative complications were body mass index (OR 1.1, P < 0.01) and smoking (OR 2.2, P < 0.01). CONCLUSIONS: For patients with breast cancer, bilateral mastectomy is associated with an increased risk of wound and overall postoperative complications. Discussion of these outcomes is imperative when counseling women contemplating CPM.

Context dependent memory in two learning environments: the tutorial room and the operating theatre.

BACKGROUND: Psychologists have previously demonstrated that information recall is context dependent. However, how this influences the way we deliver medical education is unclear. This study aimed to determine if changing the recall context from the learning context affects the ability of medical students to recall information. METHODS: Using a free recall experimental model, fourteen medical student participants were administered audio lists of 30 words in two separate learning environments, a tutorial room and an operating theatre. They were then asked to recall the words in both environments. While in the operating theatre participants wore appropriate surgical clothing and assembled around an operating table. While in the tutorial room, participants dressed casually and were seated around a table. Students experienced the same duration (15 minutes) and disruption in both environments. RESULTS: The mean recall score from the 28 tests performed in the same environment was 12.96 +/- 3.93 (mean, SD). The mean recall score from the 28 tests performed in an alternative environment to the learning episode was 13.5 +/- 5.31(mean, SD), indicating that changing the recall environment from the learning environment does not cause any statistical difference (p=0.58). The average recall score of participants who learned and recalled in the tutorial room was 13.0 +/- 3.84 (mean, SD). The average recall score of participants who learnt and recalled in the operating theatre was 12.92 +/- 4.18 (mean, SD), representing no significant difference between the two environments for learning (p=0.4792). CONCLUSIONS: The results support the continued use of tutorial rooms and operating theatres as appropriate environments in which to teach medical students, with no significant difference in information recall seen either due to a same context effect or specific context effect.

Teaching strategies for shared decision-making within the context of evidence-based healthcare practice: A scoping review.

OBJECTIVE: To describe the nature of teaching Shared Decision Making (SDM) within the context of Evidence Based Practice (EBP) to support development of contemporaneous EBP education programmes for healthcare learners. METHODS: A scoping review following the Joanna Briggs Institute (JBI) guidance was conducted with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) used to guide reporting. RESULTS: The narrative overview of 23 studies provides insight into the 'what' and 'how' of teaching SDM within the context of EBP education. A minority of studies explicitly and concurrently incorporated EBP and SDM in terms of how programme content was organised. Teaching strategies most often used regardless of learner cohort or setting included didactic, face-to-face lectures, together with role-play/modelling, small group workshops and video recordings. Programme evaluation outcomes predominantly focused on participant reactions to training and participant learning. CONCLUSION: While a disconnect between EBP and SDM remains evident in healthcare programmes, increased recognition by educators to actively facilitate this interdependent relationship is emerging. PRACTICE IMPLICATIONS: Intentionally structuring learning activities in a manner which demonstrates the relevance and interdependence of SDM and EBP may mitigate 'learning silos' and enhance learners' abilities to make connections required in practice.

Prophylactic aspirin intake and breast cancer risk; A systematic review and meta-analysis of observational cohort studies.

Breast Cancer (BC) is the most common cancer amongst women. The chemo-preventative effects of aspirin on breast cancer have been demonstrated in several longitudinal studies however previous meta-analysis have shown inconsistent results. This study aimed to assess the relationship between aspirin use and BC risk, and to determine if there is a dose-response relationship between aspirin and BC risk. Studies incorporating BC risk with aspirin use published within the last twenty years were included. The study report is based on the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology. Twenty-eight cohort studies that reported BC incidence during a follow up of 4.4-32 years were included. Compared to non-users, aspirin users had a reduced risk of BC (HR = 0.91, c.i 0.81-0.97, p = 0.002). There was no obvious association between BC risk reduction and aspirin dose (HR = 0.94, c.i 0.85-1.04) or duration (HR = 0.86, c.i 0.71-1.03). Frequency, however, was associated with a reduced risk of BC (HR = 0.90, c.i 0.82-0.98). A risk reduction was observed in oestrogen receptor (ER) positive tumours (HR = 0.90, c.i 0.86-0.96, p = 0.0004) while no relationship was observed with ER negative tumours (HR = 0.94, c.i 0.85-1.05). This meta-analysis found an association between aspirin intake and BC risk reduction. A more favourable outcome was noted with ingestion of greater than 6 tablets of aspirin per week. Aspirin had a significant risk reduction in patients with ER positive tumours compared to ER negative BC.