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Background: oestrogen receptor positive/ human epidermal growth factor receptor positive (ER+/HER2+) breast cancers (BCs) are less responsive to endocrine therapy than ER+/HER2- tumours. Mechanisms underpinning the differential behaviour of ER+HER2+ tumours are poorly characterised. Our aim was to identify biomarkers of response to 2 weeks’ presurgical AI treatment in ER+/HER2+ BCs. Methods: all available ER+/HER2+ BC baseline tumours (n=342) in the POETIC trial were gene expression profiled using BC360™ (NanoString) covering intrinsic subtypes and 46 key biological signatures. Early response to AI was assessed by changes in Ki67 expression and residual Ki67 at 2 weeks (Ki67 2wk). Time-To-Recurrence (TTR) was estimated using Kaplan-Meier methods and Cox models adjusted for standard clinicopathological variables. New molecular subgroups (MS) were identified using consensus clustering. Findings: HER2-enriched (HER2-E) subtype BCs (44.7% of the total) showed poorer Ki67 response and higher Ki67 2wk (p2wk. Five new MS that were associated with differential response to AI were identified. HER2-E had significantly poorer TTR compared to Luminal BCs (HR 2.55, 95% CI 1.14–5.69; p=0.0222). The new MS were independent predictors of TTR, adding significant value beyond intrinsic subtypes. Interpretation: our results show HER2-E as a standardised biomarker associated with poor response to AI and worse outcome in ER+/HER2+. HRD, TP53 mutational score and immune-tumour tolerance are predictive biomarkers for poor response to AI. Lastly, novel MS identify additional non-HER2-E tumours not responding to AI with an increased risk of relapse. Funding: Cancer Research UK (CRUK/07/015).

Objective\ud \ud Research is needed to understand how Shared Decision-Making (SDM) is enacted in routine clinical settings. We aimed to 1) describe the process of SDM between clinicians and patients; 2) examine how well the SDM process compares to a prescriptive model of SDM, and 3) propose a descriptive model based on observed SDM in routine practice.\ud Methods\ud \ud Patients with chronic kidney disease and early stage breast cancer were recruited consecutively via Cardiff and Vale University Health Board (UK) teams. Consultations were audio-recorded, transcribed and thematically analysed.\ud Results\ud \ud Seventy-six consultations were observed: 26 pre-dialysis consultations and two consultations each for 25 breast cancer patients. Key stages of the ‘Three Talk Model’ were observed. However, we also observed more elements and greater complexity: a distinct preparation phase; tailored and evolving integrative option conversation; patients and clinicians developing ‘informed preferences’; distributed and multi-stage decisions; and a more open-ended planning discussion. Use of decision aids was limited.\ud Conclusion\ud \ud A more complex picture was observed compared with previous portrayals in current theoretical models.\ud Practice iImplications\ud \ud The model can provide a basis for future training and initiatives to promote SDM, and tackle the gap between what is advocated in policy, but rarely achieved in practice.

ObjectivesTo examine how observer and self-report measures of shared decision-making (SDM) evaluate the decision-making activities that patients and clinicians undertake in routine consultations.DesignMulti-method study using observational and self-reported measures of SDM and qualitative analysis.SettingBreast care and predialysis teams who had already implemented SDM.ParticipantsBreast care consultants, clinical nurse specialists and patients who were making decisions about treatment for early-stage breast cancer. Predialysis clinical nurse specialists and patients who needed to make dialysis treatment decisions.MethodsConsultations were audio recorded, transcribed and thematically analysed. SDM was measured using Observer OPTION-5 and a dyadic SureScore self-reported measure.ResultsTwenty-two breast and 21 renal consultations were analysed. SureScore indicated that clinicians and patients felt SDM was occurring, but scores showed ceiling effects for most participants, making differentiation difficult. There was mismatch between SureScore and OPTION-5 score data, the latter showing that each consultation lacked at least some elements of SDM. Highest scoring items using OPTION-5 were ‘incorporating patient preferences into decisions’ for the breast team (mean 18.5, range 12.5–20, SD 2.39) and ‘eliciting patient preferences to options’ for the renal team (mean 16.15, range 10–20, SD 3.48). Thematic analysis identified that the SDM encounter is difficult to measure because decision-making is often distributed across encounters and time, with multiple people, it is contextually adapted and can involve multiple decisions.ConclusionsSelf-reported measures can broadly indicate satisfaction with SDM, but do not tell us about the quality of the interaction and are unlikely to capture the multi-staged nature of the SDM process. Observational measures provide an indication of the extent to which elements of SDM are present in the observed consultation, but cannot explain why some elements might not be present or scored lower. Findings are important when considering measuring SDM in practice.

Background Proven benefits of Shared Decision Making (SDM) include improved patient knowledge, involvement and confidence in making decisions. Although widely advocated in policy, SDM is still not widely implemented in practice. A common patient‐reported barrier is feeling that “doctor knows best”; thus, patients often defer decisions to the clinician. Objective To examine the nature of the discourse when patients ask clinicians for a treatment recommendation during consultations when treatment decisions are being shared and to examine clinicians’ strategies used in response. Design, Setting and Participants Theme‐orientated discourse analysis was performed on eight audio‐recordings of breast cancer diagnostic consultations in which patients or their partners attempted to defer treatment decisions to the clinician. Clinicians were trained in SDM. Results Tension was evident in a number of consultations when treatment recommendations were requested. Clinicians responded to recommendation requests by explaining why the decision was being shared (personal nature of the decision, individual preferences and equivalent survival outcomes of treatment options). There was only one instance where a clinician gave a treatment recommendation. Discussion and Conclusions Strategies for clinicians to facilitate SDM when patients seem to defer decisional responsibility include being clear about why the decision is being shared, acknowledging that this is difficult and making patients feel supported. When patients seek guidance, clinicians can provide a recommendation if grounded in an understanding of the patient's values.

Endocrine therapy is an important way to manage cancers whose growth is dependent on hormonal stimulation, namely breast, prostate and endometrial cancers. This article describes the principles behind their use, the indications for use, the different medications available and some of the evidence to support their use. Endocrine therapies avoid the toxicities associated with chemotherapy, but often have side effects that impact on quality of life too.

The role of the surgeon in cancer management has evolved and now encompasses roles in diagnosis, staging, screening, prevention, and palliative care as well as the traditional role in surgical excision. The UK has three established cancer screening programmes for breast, cervical and colorectal cancer, where surgeons are required to perform clinical assessment, invasive diagnostic biopsies and surgical treatments. There are many different surgical techniques available for surgical treatment of cancer, many of which allow a minimally invasive approach including laparoscopic, endoscopic and robotic surgery. The progress of medical genetics and gene profiling now allows identification of ‘at-risk’ individuals for specific types of cancer where prophylactic or risk reducing surgery may be of patient benefit. Cancer treatment may result in disfigurement and loss of function, so reconstructive surgery is an integral part of cancer management. Patients with advanced disease can often be helped by surgery to relieve symptoms associated with their disease and improve their quality of life.

The incidence of cancer continues to rise in western countries, although slower than in previous decades. In the UK 24% of all deaths are caused by cancer. The role of surgery in cancer management has expanded over the last few decades to include screening, prevention, diagnosis and staging, reconstruction and palliation. In UK, the breast, bowel and cervical national screening programmes rely on surgeons to perform invasive diagnostic procedures. Genetic testing enables identification of carriers of pathological genetic mutations who are at high risk of developing cancer and might benefit from ‘risk-reducing’ surgery. Advances in surgical technology have led to a variety of new techniques being available to surgeons and cancer patients for diagnostic and therapeutic purposes, including vacuum-assisted devices, photodynamic therapy, radio frequency ablation, cryosurgery and microwave ablation. Oncological surgical procedures often result in disfigurement, mutilation or functional loss, and restorative surgery has become an integral part in the management of cancer patients with the ultimate aim of improving their quality of life. In incurable cancer patients, palliative surgery can be justified to reduce the severity of symptoms and improve the quality of life, where conservative strategies or less invasive interventions have failed or are not appropriate.

Endocrine therapy is an important agent in the treatment of cancers whose growth is dependent on hormone stimulation, namely breast, endometrial and prostatic. In this article the main endocrine therapies used for each of these cancers, the principles behind their use, indications for use and their limitations are discussed.

Due to improved diagnostic techniques, most breast surgery is performed for the treatment of breast cancer after a preoperative diagnosis has been made. In the management of breast cancer, there has been a trend towards breast conservation, but some patients require or request a mastectomy. Axillary surgery remains controversial and the new technique of sentinel node biopsy (which aims to increase the accuracy and decrease the morbidity associated with axillary surgery) is currently being evaluated in the UK. Breast reconstruction has also improved with development of new implants and techniques using pedicled and free myocutaneous flaps. Many breast surgeons have developed these skills so that they can provide a comprehensive service to breast cancer patients.

This paper presents the results of a multi-method research project investigating the psychological distress associated with waiting for results of diagnostic investigations in a delayed-results breast clinic. A cohort of 126 women completed standardized psychometric instruments to assess anxiety, mood and coping over 3 days. Semi-structured interviews were conducted with 20 respondents. The findings indicate that waiting sustained but did not exacerbate psychological distress. Peri-diagnostic anxiety, depression, uncertainty and confusion were associated with anxiety levels immediately following triple assessment. Women leaving the clinic with low anxiety retained this composure throughout the peri-diagnostic period. Those in the moderate and high anxiety groups recorded sustained anxiety, depression, uncertainty and confusion, with mean scores comparable to and exceeding those reported by psychiatric out-patients. Coping during the waiting period was typically accomplished by emotion-focused strategies. Qualitative data suggested the delayed-results clinic structure may facilitate psychological preparation for test results.

Genetic testing is now feasible for a growing number of cancers. Although the implications for unaffected relatives have been widely described, the impact of the tests on affected individuals are often not recognized. We present and discuss four cases that highlight some of the issues-for example, feelings of guilt and anxiety, intrafamilial conflict, and support needs-that may arise in testing affected individuals. We offer some suggestions to aid in the approach to such testing.

Despite exciting advances in drug treatment, surgery remains the mainstay of breast cancer treatment. Diagnostic techniques have improved so that patients have a diagnosis of cancer before surgery is undertaken, so that they are able to discuss it in an informed manner. There has been an increasing trend towards breast conservation treatment as patients are diagnosed with early breast cancers. Mastectomy, however, is still needed in a number of cases. There have recently been significant developments in the assessment of the axilla with the development of the sentinel node technique. This is a useful diagnostic procedure to avoid the side effects of axillary clearance, but axillary node clearance is still the best treatment for pathological lymph nodes.

Surgical site infection (SSI) is the fourth commonest healthcare-associated infection and complicates at least 5% of open operations. In a randomized clinical trial, antimicrobial-coated sutures were compared with their conventional counterparts, polyglactin and poliglecaprone, for skin closure after breast cancer surgery to assess their role in reducing the rate of SSI.Between November 2008 and February 2011, 150 female patients presenting with breast cancer to a single center were randomized to skin closure with antimicrobial-coated or plain sutures. Postoperatively, SSI was defined using the U.S. Centers for Disease Control and Prevention (CDC) definitions and scored using the ASEPSIS or Southampton systems by trained, blinded observers with close post-discharge surveillance and patient diaries. Surgeons and patients were blinded to the type of suture used.Using CDC criteria, the overall rate of SSI was 18.9% at six weeks. Six patients (4.7%) needed intervention or readmission for SSI. Skin closure with antimicrobial sutures showed a non-statistically significant reduction in the SSI rate, to 15.2%, compared with conventional sutures (22.9%). A uniform tendency for fewer SSIs in the antimicrobial-coated suture group was found using ASEPSIS and Southampton scores, but again, the difference was not statistically significant.The previously reported high rate of SSI related to breast surgery was confirmed. Using statistical modeling and earlier reports, the study was powered to show a difference using ASEPSIS scores, but the modification used in this trial failed to find a difference. Finding a statistically significant difference would have needed two to three times the number of patients recruited. Further evaluation of antimicrobial-coated sutures is merited, particularly if used as part of a care bundle to reduce SSI after breast cancer surgery.

Loss of adhesion is a fundamental step in the metastatic cascade. Desmosomal cadherins, Desmoglein (Dsg) and Desmocollin (Dsc) are a novel group of adhesion molecules. Aims were to demonstrate expression of Dsg2 and E-cadherin in breast cancer cells and assess their role in invasion and motility. Immunofluorescence and Western blotting were used to demonstrate expression of Dsg2 and E-cadherin in 3 breast cancer cell lines (MDA MB 231, MCF7 and BT474). Functional studies included cell-cell aggregation, in vitro invasion and colloidal gold phagokinetic tracking assays. All 3 cell lines expressed Dsg2. MCF7 and BT474 cells were E-cadherin positive, MDA 231 was negative. Cell aggregation was reduced, in vitro invasion and motility were increased in Dsg2 or E-cadherin Mab pre-treated cells. Dsg2 present in breast cancer cells may act as a tumour suppressor molecule.

Background: Metastasis to the breast is rare. Its management differs from that of primary breast cancer, as illustrated by this case of a colonic metastasis to the breast. Case Report: A 78-year-old woman presented with a breast lump 16 months after a palliative colonic resection for an obstructing colon cancer (T4 N0 M1). Core biopsy of the breast lump revealed morphological features identical to the original bowel cancer. In view of her progressive metastatic disease, the breast lump was simply observed. She passed away 4 months later from advanced intra-abdominal carcinomatosis. Discussion: There are 19 cases of colonic metastasis to the breast in the literature. In the literature, colonic metastases to the breast are usually excised. Conclusion: Excision of a colonic metastasis to the breast can be avoided if the patient’s life expectancy is short.

This article reports a study evaluating the sources and availability of career advice available to students in UK medical schools in order to ascertain the need for an enhanced role for careers information in undergraduate curricula.

Background. Intra-operative assessment is not routinely performed in the UK due to poor sensitivity of available methods and overburdened pathology resources. We conducted a prospective clinical feasibility study of the GeneSearch™ Breast Lymph Node (BLN) Assay (Veridex, LLC, Warren, NJ) to confirm its potential usefulness within the UK healthcare system. Methods In the assay 50% of the lymph node was processed to detect the presence of cytokeratin-19 and mammaglobin mRNA. The assay was calibrated to detect metastases >0.2 mm. Assay results were compared to H&E performed on each face of ~2 mm alternating node slabs and 3 additional sections cut at ~150 μm interval from each face of the node slab. Results 124 sentinel lymph nodes were removed from 82 breast cancer patients. The assay correctly identified all 6 patients with sentinel node macrometastases (>2.0 mm), and 2 of 3 patients with sentinel node micrometastases (0.2–2.0 mm). Sentinel lymph nodes in 4 patients were assay positive but histology negative. Two of these four patients had isolated tumor cells seen by histology. The overall concordance with histology was 93.9% (77/82), with sensitivity of 88.9% (8/9, 95% CI 56.5–98%), specificity of 94.6% (69/73, 95% CI 86.7–97.8%), positive predictive value of 66.7% (8/12, 95% CI 39.1–86.2%) and negative predictive value of 98.6% (69/70, 95% CI 92.3–99.7%). The assay was performed in a median time of 32 min (range 26–69 min). Conclusion Intra-operative assessment of sentinel lymph node can be performed rapidly and accurately using the GeneSearch™ BLN Assay.

BACKGROUND: The role of sentinel lymph node biopsy (SLNB) in patients with a core needle-biopsy diagnosis of ductal carcinoma in situ (DCIS) has been intensely debated. Core needle-biopsy has an inherent sampling error leading to histologic underestimation of invasive disease. If SLNB is not performed at the time of the definitive operative procedure, patients found to have an invasive cancer, will require a second operative procedure. The study was designed to determine when the risk of finding invasive disease on final pathology in patients with an initial diagnosis of DCIS was sufficiently high to justify the use of SLNB. METHODS: We identified 587 women with an initial core needle-biopsy diagnosis of DCIS in the prospective Breast Test Wales (BTW) database from 1995 through 2005. A variety of clinical, mammographic and histologic features were identified and correlated with the presence of invasion at excision using univariate and multivariate analyses. RESULTS: Median age of patients at the time of diagnosis was 58 years (range 41 to 83 years). 201 patients (36%) were treated by mastectomy and 354 (64%) by breast conservation surgery. 220 of 587 patients (38%) were found to have invasive disease on final pathology. On univariate analysis, the rate of upstaging was related to the presence of a clinically palpable mass and size of the mass (both p

The skin is a valuable organ for the development and exploitation of gene medicines. Delivering genes to skin is restricted however by the physico-chemical properties of DNA and the stratum corneum (SC) barrier. In this study, we demonstrate the utility of an innovative technology that creates transient microconduits in human skin, allowing DNA delivery and resultant gene expression within the epidermis and dermis layers. The radio frequency (RF)-generated microchannels were of sufficient morphology and depth to permit the epidermal delivery of 100 nm diameter nanoparticles. Model fluorescent nanoparticles were used to confirm the capacity of the channels for augmenting diffusion of macromolecules through the SC. An ex vivo human organ culture model was used to establish the gene expression efficiency of a I²-galactosidase reporter plasmid DNA applied to ViaDermâ„¢ treated skin. Skin treated with ViaDermâ„¢ using 50 I¼m electrode arrays promoted intense levels of gene expression in the viable epidermis. The intensity and extent of gene expression was superior when ViaDermâ„¢ was used following a prior surface application of the DNA formulation. In conclusion, the RF-microchannel generator (ViaDermâ„¢) creates microchannels amenable for delivery of nanoparticles and gene therapy vectors to the viable region of skin.

This study aims to examine relationships between demographic factors and treatment choice for early breast cancer (T2/N

tumour responded very well to the 5-fluorouracil treatment and References shrinkage of the pancreatic tumour was confirmed radiologically 1. Service FJ, McMahon MM, O’Brien PC, Ballard DJ. in just 6 weeks. The reduction in size of the tumour coupled with Functioning insulinoma: incidence, recurrence and long term the slow growing nature of this tumour prompted us to perform survival of patients: a 60 year study. Mayo Clin Proc 1991; 66: a resection. Thus, pre-operative adjuvant chemotherapy plays a 711–9. significant role in downstaging the endocrine pancreatic tumour. 2. Moldrow RE, Connelly RR. Epidemiology of pancreatic Secondly, although a curative resection may not have been achieved endocrine tumours of the pancreas. Analysis of autopsy cases. despite radical excision, the patient remained well after 13 years Dig Dis Sci 1968; 36: 933–42. following the Whipple’s procedure. Indeed her recent CT failed to 3. Bliss RD, Carter PB, Lennard TWJ. Insulinoma: a review of show any evidence of recurrent disease. current management. Surg Oncol 1997; 6: 49–59. In conclusion, chemotherapy has a significant role to play in the 4. Lo CY, Lam KY, Kung AW, Lam KS, Tung PH, Fan ST. management of malignant insulinomas. Although non-functioning Pancreatic insulinomas. A 15 year experience. Arch Surg 1997; malignant insulinomas presenting with obstructive features are rare, 132: 926–30. they may be successfully treated by surgery. If this is not feasible, 5. Grant CS. Surgical management of malignant islet cell tumours. surgical debulking of the primary and metastatic lesions produce World J Surg 1993; 17: 498–503. 6. Van Heerden J. Pancreatic resection for carcinoma of the good palliation and increased survival. Due to the slow nature of pancreas: Whipples versus total pancreatectomy—an their growth it is imperative to follow-up these patients for many institutional perspective. World J Surg 1994; 8: 880. years. 7. Doppman JL, Miller DL, Chang R. Intraarterial calcium stimulation test for detection of insulinomas. World J Surg 1993; 17: 439–43.

Breast pain is a common condition affecting most women at some stage in their reproductive life. Mastalgia is resistant to treatment in 6% of cyclical and 26% non-cyclical patients. Surgery is not widely used to treat this condition and only considered in patients with severe mastalgia resistant to medication. The aims of this study were to audit the efficacy of surgery in severe treatment resistant mastalgia and to assess patient satisfaction following surgery. This is a retrospective review of the medical records of all patients seen in mastalgia clinic in the University Hospital of Wales, Cardiff since 1973. A postal questionnaire was distributed to all patients who had undergone surgery. Results showed that of the 1054 patients seen in mastalgia clinic, 12 (1.2%) had undergone surgery. Surgery included 8 subcutaneous mastectomies with implants (3 bilateral, 5 unilateral), 1 bilateral simple mastectomy and 3 quadrantectomies (1 having a further simple mastectomy). The median duration of symptoms was 6.5 years (range 2-16 years). Five patients (50%) were pain free following surgery, 3 developed capsular contractures and 2 wound infections with dehiscence. Pain persisted in both patients undergoing quadrantectomy. We conclude that surgery for mastalgia should only be considered in a minority of patients. Patients should be informed of possible complications inherent of reconstructive surgery and warned that in 50% cases their pain will not be improved.