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Objectives: The cancer multidisciplinary team (MDT) meeting (MDM) is regarded as the best platform to reduce unwarranted variation in cancer care through evidence-compliant management. However, MDMs are often overburdened with many different agendas and hence struggle to achieve their full potential. The authors developed an interactive clinical decision support system called MATE (Multidisciplinary meeting Assistant and Treatment sElector) to facilitate explicit evidence-based decision making in the breast MDMs. Design: Audit study and a questionnaire survey. Setting: Breast multidisciplinary unit in a large secondary care teaching hospital. Participants: All members of the breast MDT at the Royal Free Hospital, London, were consulted during the process of MATE development and implementation. The emphasis was on acknowledging the clinical needs and practical constraints of the MDT and fitting the system around the team's workflow rather than the other way around. Delegates, who attended MATE workshop at the England Cancer Networks' Development Programme conference in March 2010, participated in the questionnaire survey. Outcome measures: The measures included evidence- compliant care, measured by adherence to clinical practice guidelines, and promoting research, measured by the patient identification rate for ongoing clinical trials. Results: MATE identified 61% more patients who were potentially eligible for recruitment into clinical trials than the MDT, and MATE recommendations demonstrated better concordance with clinical practice guideline than MDT recommendations (97% of MATE vs 93.2% of MDT; N=984). MATE is in routine use in breast MDMs at the Royal Free Hospital, London, and wider evaluations are being considered. Conclusions: Sophisticated decision support systems can enhance the conduct of MDMs in a way that is acceptable to and valued by the clinical team. Further rigorous evaluations are required to examine cost-effectiveness and measure the impact on patient outcomes. The decision support technology used in MATE is generic and if found useful can be applied across medicine. [ABSTRACT FROM AUTHOR]

Purpose: Tumour angiogenesis is an independent and strong prognostic factor in early breast carcinoma. We performed this study to investigate the ability of F-FDG to detect angiogenesis in early breast carcinoma using PET/CT. Methods: Twenty consecutive patients with early (T1-T2) breast carcinoma were recruited prospectively for 18F-FDG PET/CT. The PET/CT data were used to calculate whole tumour maximum standardized uptake value (SUV) and mean standardized uptake value (SUV). All patients underwent subsequent surgery without prior chemotherapy or radiotherapy. The excised tumour underwent immunohistochemistry for vascular endothelial growth factor (VEGF), CD105 and glucose transporter protein 1 (GLUT1). Results: The SUV showed the following correlation with tumour histology: CD105: r = 0.60, p = 0.005; GLUT1: r = 0.21, p = 0.373; VEGF: r = −0.16, p = 0.496. The SUV showed the following correlation with tumour histology: CD105: r = 0.65, p = 0.002; GLUT1: r = 0.34, p = 0.144; VEGF: r = −0.18, p = 0.443 Conclusion: F-FDG uptake is highly significantly associated with angiogenesis as measured by the immunohistochemistry with CD105 for new vessel formation. Given that tumour angiogenesis is an important prognostic indicator and a predictor of treatment response, F-FDG PET may have a role in the management of primary breast cancer patients even in early-stage disease. [ABSTRACT FROM AUTHOR]

BACKGROUND: To study the value of periareolar intra-derma! injection of Tc-99m sestamibi (MIBI) for sentinel node mapping in breast carcinoma. MATERIAL AND METHODS: Fifty patients with early-stage breast cancer were included in our study. 17.5 MBq Tc-99m-MIBI was injected intradermally to 25 patients and the remainders were injected with the same dose of Tc-99m-antimony sulphide col!oid. Anterior and lateral static images were taken at 2 minutes. If sentinel lymph node was not detected, delayed imaging.by up to 180 minutes was carried out. The patients were operated on 2-4 hours post-injection. Sentinel lymph node biopsy was performed by the aid of gamma probe and blue dye during surgery. RESULTS: In the Tc-99m-MIBI group, 23 patients had lymph nodes on scintigraphy images, and sentinel nodes were detected during surgery in all 23 patients. In the Tc-99m-antimony sulphide colloid group, 24 patients had lymph nodes on scintigraphy images, and sentinel nodes were identified during surgery in 24 patients. CONCLUSIONS: We concluded that 99mTc-MIBI is a suitable radiopharmaceutical for sentinel node detection. [ABSTRACT FROM AUTHOR]

Abstract Implant based reconstruction accounts for over half of breast reconstruction performed in the UK. Patients with implant based breast reconstructions undergoing post mastectomy radiotherapy are at increased risk of capsular contracture and reconstructive failure. This study sought to determine the effect of treatment dose radiotherapy on the bulk mechanical, surface chemical properties of silicone implants as well as their cellular response. Silicone breast implant shells were submitted to treatment dose radiotherapy, 2.67 Gy (one daily fraction) and 40.05 Gy (15 fractions) using non-irradiated shells as controls. Bulk mechanical and surface chemical properties of the shells were evaluated using tensile and tear testing, attenuated total reflectance – fourier transform infrared spectroscopy (ATR-FTIR), water contact angle measurements. HDFa cells were seeded on the shells and Alamar Blue assay was performed to study cell metabolic activity. Cell morphology was evaluated using phalloidin and DAPI staining. There was no significant difference in tensile, tear strength and Young's modulus however there was reduction in maximum elongation following irradiation. Irradiation of the shells did not significant alter spectroscopy measurements nor wettability of the shells. Cell metabolism was not significantly affected by irradiation. Further analysis is warranted of the micromechanical properties to fully elucidate the effect of irradiation on the breast implant which could explain the increased rate of capsular contracture and reconstructive failure in patients undergoing post-mastectomy radiotherapy. Highlights • Implant based breast reconstruction (IBBR) accounts for over half of breast reconstructions performed in the UK • Patients with IBBR who receive post mastectomy radiotherapy are at increased risk of implant related complication • Implants tested with radiation therapy demonstrated no overall change in mechanical or surface chemical properties [ABSTRACT FROM AUTHOR]

There is considerable interest in biomedical applications of quantum dot (QD) nanoparticles, in particular their use as imaging agents for diagnostic applications. In order to investigate the in vivo biodistribution and the potential toxicity of quantum dots (QDs), it is crucial to develop pharmacokinetic (PK) models as basis for prediction of QDs exposure profiles over time. Here, we investigated the in vivo biodistribution of novel indium-based QDs in mice for up to three months after intravenous administration and subsequently developed a translational population PK model to scale findings to humans. This evaluation was complemented by a comprehensive overview of the in vivo toxicology of QDs in rats. The QDs were primarily taken up by the liver and spleen and were excreted via hepatobiliary and urinary pathways. A non-linear mixed effects modelling approach was used to describe blood and organ disposition characteristics of QDs using a multi-compartment PK model. The observed blood and tissue exposure to QDs was characterised with an acceptable level of accuracy at short and long-term. Of note is the fast distribution of QDs from blood into liver and spleen in the first 24 h post-injection (half-life of 28 min) followed by a long elimination profile (half-life range: 47-90 days). This is the first study to assess the PK properties of QDs using a population pharmacokinetic approach to analyse in vivo preclinical data. No organ damage was observed following systemic administration of QDs at doses as high as 48 mg/kg at 24 h, 1 week and 5 weeks post-injection. In conjunction with the data arising from the toxicology experiments, PK parameter estimates provide insight into the potential PK properties of QDs in humans, which ultimately allow prediction of their disposition and enable optimisation of the design of first-in-human QDs studies. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Introduction: Triple negative breast cancer (TNBC) is a subtype of breast cancer characterised by its high tumourigenic, invasive, and immunosuppressive nature. Photodynamic therapy (PDT) is a focal therapy that uses light to activate a photosensitizing agent and induce a cytotoxic effect. 5-aza-2'-deoxycytidine (5-ADC) is a clinically approved immunomodulatory chemotherapy agent. The mechanism of the combination therapy using PDT and 5-ADC in evoking an anti-tumour response is not fully understood., Methods: The present study examined whether a single dose of 5-ADC enhances the cytotoxic and anti-tumour immune effect of low dose PDT with verteporfin as the photosensitiser in a TNBC orthotopic syngeneic murine model, using the triple negative murine mammary tumour cell line 4T1. Histopathology analysis, digital pathology and immunohistochemistry of treated tumours and distant sites were assessed. Flow cytometry of splenic and breast tissue was used to identify T cell populations. Bioinformatics were used to identify tumour immune microenvironments related to TNBC patients., Results: Functional experiments showed that PDT was most effective when used in combination with 5-ADC to optimize its efficacy. 5-ADC/PDT combination therapy elicited a synergistic effect in vitro and was significantly more cytotoxic than monotherapies on 4T1 tumour cells. For tumour therapy, all types of treatments demonstrated histopathologically defined margins of necrosis, increased T cell expression in the spleen with absence of metastases or distant tissue destruction. Flow cytometry and digital pathology results showed significant increases in CD8 expressing cells with all treatments, whereas only the 5-ADC/PDT combination therapy showed increase in CD4 expression. Bioinformatics analysis of in silico publicly available TNBC data identified BCL3 and BCL2 as well as the following anti-tumour immune response biomarkers as significantly altered in TNBC compared to other breast cancer subtypes: GZMA, PRF1, CXCL1, CCL2, CCL4, and CCL5. Interestingly, molecular biomarker assays showed increase in anti-tumour response genes after treatment. The results showed concomitant increase in BCL3, with decrease in BCL2 expression in TNBC treatment. In addition, the treatments showed decrease in PRF1, CCL2, CCL4, and CCL5 genes with 5-ADC and 5-ADC/PDT treatment in both spleen and breast tissue, with the latter showing the most decrease., Discussion: To our knowledge, this is the first study that shows which of the innate and adaptive immune biomarkers are activated during PDT related treatment of the TNBC 4T1 mouse models. The results also indicate that some of the immune response biomarkers can be used to monitor the effectiveness of PDT treatment in TNBC murine model warranting further investigation in human subjects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Banerjee, Acedo, El Sheikh, Harati, Meecham, Williams, Gerard, Keshtgar, MacRobert and Hamoudi.)

Introduction: Breast implants are associated with complications such as capsular contracture, implant rupture and leakage often necessitating further corrective surgery. Re-operation rates have been reported to occur in up to 15.4% of primary augmentation patients and up to 27% in primary reconstructions patients within the first three years (Cunningham, 2007). The aim of this study was to examine the mechanical and surface chemical properties as well as the fibroblast response of retrieved breast implants in our unit to determine the in vivo changes which occur over time., Methods: Ethical approval was obtained. 47 implants were retrieved. Implantation time ranged from 1 month to 388 months (Mean 106.1 months). Tensile strength, elongation, Young's modulus and tear strength properties were measured using Instron 5565 tensiometer on anterior and posterior aspects of the implant. Attenuated total reflectance-fourier transform infra-red spectroscopy (ATR-FTIR), wettability and scanning electron microscopy (SEM) analysis was performed on the shell surfaces. Bicinchoninic acid assay was performed to determine shell protein content. The fibroblast response was determined by seeding HDFa cells on the retrieved implants and cell metabolism measured using Alamar Blue™ assay., Results: Mechanical properties fall with increasing duration of implantation. There were no significant changes in ATR-FTIR spectra between ruptured and intact implants nor significant changes in wettability in implants grouped into 5 year categories. SEM imaging reveals surface degradation changes with increasing duration of implantation., Conclusions: With increasing duration of implantation, mechanical properties of the breast implants fall. However this was not associated with surface chemical changes as determined by ATR-FTIR and wettability nor protein content of the shells. Thus the reduction in mechanical properties is associated with breast implant failure but further research is required to elucidate the mechanisms., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Cutaneous recurrence from breast cancer can pose a clinical challenge. It might be the only disease site, or could be part of disseminated disease, and often profoundly affects quality of life. Electrochemotherapy is a palliative treatment using electric pulses to locally permeabilize tumor cells and thereby significantly increase bleomycin cytotoxicity. Collaborating with the International Network for Sharing Practice on ElectroChemoTherapy (INSPECT), we consecutively and prospectively accrued data on patients treated with electrochemotherapy for cutaneous metastases from breast cancer., Patients and Methods: Patients were treated with electrochemotherapy at 10 European centers. Under either local or general anaesthesia patients were treated with either local injection (1000 IU/mL intratumoral) or systemic infusion (15,000 IU/m 2 ) of bleomycin., Results: One hundred nineteen patients were included at 10 institutions in the INSPECT network. The primary location was the chest (89%), the median diameter of the cutaneous metastases was 25 mm. Ninety patients were available for response evaluation after 2 months. Complete response was observed in 45 patients (50%), partial response in 19 (21%), stable disease in 16 (18%), and progressive disease in 7 (8%). Three patients were not evaluable. Common side effects were ulceration, long-lasting hyperpigmentation, and low-grade pain. No serious adverse events were observed., Conclusion: Electrochemotherapy showed high response rates after a single treatment. Electrochemotherapy has few side effects and can be used as an adjunct to systemic therapies or as a solo treatment. We therefore recommend considering electrochemotherapy for patients with cutaneous metastases., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Post-mastectomy radiation therapy (PMRT) is known to increase the complication rate and implant loss in implant-based breast reconstruction. The purpose of this study was to systematically review the literature regarding the outcome of PMRT delivered to the permanent/definitive implant., Methods: Systematic review and meta-analysis of studies involving immediate implant-based reconstruction and PMRT when delivered to the permanent implant., Results: Seven studies included 2921 patients (520 PMRT, 2401 control). PMRT was associated with significant increase in capsular contracture (7 studies, 2529 patients, 494 PMRT, 2035 control, OR 10.21, 95% CI 3.74 to 27.89, p < 0.00001). In addition, PMRT was associated with a significant increase in revisional surgery (7 studies, 2921 patients, 520 PMRT, 2401 control, OR 2.18, 95% CI 1.33 to 3.57, p = 0.002) and reconstructive failure (6 studies, 2814 patients, 496 PMRT, 2318 control, OR 2.52, 95% CI 1.48 to 4.29, p+0.0007). Moreover, it was associated with a significant reduction in patient satisfaction (4 studies, 468 patients, 138 PMRT, 294 control, OR 0.29, 95% CI 0.15 to 0.57, p = 0.0003) and cosmetic outcome (4 studies, 1317 patients, 238 PMRT, 1009 control, OR 28, 95% CI. 0.11 to 0.67, p = 0.005)., Conclusions: This meta-analysis demonstrates that within the first 5 years, post implant-based reconstruction for those patients who receive PMRT, the rates of adverse events are increased, and there is a significant reduction in patient satisfaction and cosmetic outcome., (Copyright © 2017. Published by Elsevier Ltd.)

Purpose: Access to nuclear medicine department for sentinel node imaging remains an issue in number of hospitals in the UK and many parts of the world. Sentinella ® is a portable imaging camera used intra-operatively to produce real time visual localisation of sentinel lymph nodes., Methods: Sentinella ® was tested in a controlled laboratory environment at our centre and we report our experience on the first use of this technology from UK. Moreover, preoperative scintigrams of the axilla were obtained in 144 patients undergoing sentinel node biopsy using conventional gamma camera. Sentinella ® scans were done intra-operatively to correlate with the pre-operative scintigram and to determine presence of any residual hot node after the axilla was deemed to be clear based on the silence of the hand held gamma probe., Results: Sentinella ® detected significantly more nodes compared with CGC (p < 0.0001). Sentinella ® picked up extra nodes in 5/144 cases after the axilla was found silent using hand held gamma probe. In 2/144 cases, extra nodes detected by Sentinella ® confirmed presence of tumour cells that led to a complete axillary clearance., Conclusions: Sentinella ® is a reliable technique for intra-operative localisation of radioactive nodes. It provides increased nodal visualisation rates compared to static scintigram imaging and proves to be an important tool for harvesting all hot sentinel nodes. This portable gamma camera can definitely replace the use of conventional lymphoscintigrams saving time and money both for patients and the health system., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Breast cancer is the most common female cancer, affecting approximately one in eight women during their lifetime in North America and Europe. Receptor Activator of NF-kB Ligand (RANKL), its receptor RANK and the natural antagonist osteoprotegerin (OPG) are essential regulators of bone resorption. We have initially shown that RANKL/RANK are essential for hormone-driven mammary epithelial proliferation in pregnancy and RANKL/RANK have been implicated in mammary stem cell biology. Using genetic mouse-models, we and others identified the RANKL/RANK system as a key regulator of sex hormone, BRCA1-mutation, and oncogene-driven breast cancer and we proposed that RANKL/RANK might be involved in the initiation of breast tumors. We now report that in postmenopausal women without known genetic predisposition, high RANKL and progesterone serum levels stratify a subpopulation of women at high risk of developing breast cancer 12-24 months before diagnosis (5.33-fold risk, 95%CI 1.5-25.4; P=0.02). In women with established breast cancer, we demonstrate that RANKL/OPG ratios change dependent on the presence of circulating tumor cells (CTCs). Finally, we show in a prospective human breast cancer cohort that alterations in RANKL/OPG ratios are significantly associated with breast cancer manifestation. These data indicate that the RANKL/RANK/OPG system is deregulated in post-menopausal women at high risk for breast cancer and in women with circulating tumor cells. Thus, serum levels of RANKL/OPG are potentially indicative of predisposition and progression of breast cancer in humans. Advancement of our findings towards clinical application awaits prior validation in independent patient cohorts.

Competing Interests: The authors have no conflicts of interest to declare.

The high incidence and low mortality of breast cancer surgery has led to an increasing emphasis on the cosmetic outcome of surgical treatment. Advances in aesthetic evaluation, as well as surgical planning and outcome prediction, have been investigated by using geometrically precise 3D modelling of the breast surface prior to surgery and after the procedure. However, existing solutions are based on expensive site specific setups and remain weakly validated. In this paper, we explore the possibility of using low-cost RGBD cameras as an affordable and mobile system for breast surface reconstruction. The methodology relies on sensor calibration, uncertainty-driven point filtering, dense reconstruction and subsequent multi-view joint optimization to diffuse residual pose errors. Results from a phantom study, with ground truth obtained through commercially available scanners, indicate that the approach is promising with RMS errors in order of 2 mm. A clinical study shows the practical applicability of our method and compares favourably to high-end scanning solutions.

Intra-operative radiotherapy (IORT) as a treatment for breast cancer is a relatively new technique that is designed to be a replacement for whole breast external beam radiotherapy (EBRT) in selected women suitable for breast-conserving therapy. This article reviews twelve reasons for the use of the technique, with a particular emphasis on targeted intra-operative radiotherapy (TARGIT) which uses X-rays generated from a portable device within the operating theatre immediately after the breast tumour (and surrounding margin of healthy tissue) has been removed. The delivery of a single fraction of radiotherapy directly to the tumour bed at the time of surgery, with the capability of adding EBRT at a later date if required (risk-adaptive technique) is discussed in light of recent results from a large multinational randomised controlled trial comparing TARGIT with EBRT. The technique avoids irradiation of normal tissues such as skin, heart, lungs, ribs and spine, and has been shown to improve cosmetic outcome when compared with EBRT. Beneficial aspects to both institutional and societal economics are discussed, together with evidence demonstrating excellent patient satisfaction and quality of life. There is a discussion of the published evidence regarding the use of IORT twice in the same breast (for new primary cancers) and in patients who would never be considered for EBRT because of their special circumstances (such as the frail, the elderly, or those with collagen vascular disease). Finally, there is a discussion of the role of the TARGIT Academy in developing and sustaining high standards in the use of the technique.

A novel method for rapidly detecting metastatic breast cancer within excised sentinel lymph node(s) of the axilla is presented. Elastic scattering spectroscopy (ESS) is a point-contact technique that collects broadband optical spectra sensitive to absorption and scattering within the tissue. A statistical discrimination algorithm was generated from a training set of nearly 3000 clinical spectra and used to test clinical spectra collected from an independent set of nodes. Freshly excised nodes were bivalved and mounted under a fiber-optic plate. Stepper motors raster-scanned a fiber-optic probe over the plate to interrogate the node's cut surface, creating a 20x20 grid of spectra. These spectra were analyzed to create a map of cancer risk across the node surface. Rules were developed to convert these maps to a prediction for the presence of cancer in the node. Using these analyses, a leave-one-out cross-validation to optimize discrimination parameters on 128 scanned nodes gave a sensitivity of 69% for detection of clinically relevant metastases (71% for macrometastases) and a specificity of 96%, comparable to literature results for touch imprint cytology, a standard technique for intraoperative diagnosis. ESS has the advantage of not requiring a pathologist to review the tissue sample.