BACKGROUND: Germline pathogenic variants mutations) in the BRCA1 and BRCA2 genes cause an increased risk of breast cancer and ovarian cancer. Mainstream cancer genetic testing (MCG) was introduced for breast cancer patients in our unit in 2013. Non-geneticist clinicians have been trained to offer genetic testing during initial treatment planning. We assessed the impact of timely test results on surgical decision-making. METHODS: Women who had undergone mainstream genetic testing for breast cancer between September 2013 and September 2018 were identified from a prospective database. Surgical data were collected retrospectively. RESULTS: 580 eligible women had mainstream genetic testing. For 474 this was their first breast cancer diagnosis. The median age was 46 years (interquartile range (IQR) 38-57). The indications were: age ≤45 years for 233 (49%); triple negative disease for 192 women (40.5%); bilateral breast cancer age <60 for 39 (8%) and other for 72 (14%) women. The median time for test initiation to result was 18 days (IQR 15-21). 302 (64% received results before surgery. 88% of those found to have a BRCA mutation before surgery opted for bilateral mastectomy (compared to 5% with BRCA wild type). An additional 106 patients had a new diagnosis on a background of previous treatment. Of these all with a pathogenic variant chose bilateral mastectomy. CONCLUSION: Timely BRCA gene testing influences surgeons' and patients' choice of surgery. It reassures women with a negative result and allows those with a positive result to take an active decision about the management of their future risk..

INTRODUCTION: The optimal combination of radiotherapy and breast reconstruction has not yet been defined. Post-mastectomy radiotherapy (PMRT) has deleterious effects on breast reconstruction, leading to caution amongst surgeons. Pre-operative radiotherapy (PRT) is a growing area of interest, is demonstrated to be safe, and spares autologous flaps from radiotherapy. This study evaluates the aesthetic outcome of PRT and deep inferior epigastric artery perforator (DIEP) flap reconstruction within the Pre-operative Radiotherapy And Deep Inferior Epigastric artery Perforator (DIEP) flAp (PRADA) cohort. METHODS: PRADA was an observational cohort study designed to evaluate the feasibility and safety of PRT for women undergoing neoadjuvant chemotherapy and DIEP reconstruction. Panel evaluation of 3D surface images (3D-SIs) and patient-reported outcome measures (BREAST-Q) for a subset of women in the study were compared with those of a DIEP-PMRT cohort who had undergone DIEP reconstruction and PMRT. RESULTS: Seventeen out of 33 women from the PRADA study participated in this planned substudy. Twenty-eight women formed the DIEP-PMRT cohort (median follow-up 23 months). The median (inter-quartile range [IQR]) 'satisfaction with breasts' score at 12 months for the PRADA cohort was significantly better than the DIEP-PMRT cohort (77 [72-87] versus 64 [54-71], respectively), p=0.01). Median [IQR] panel evaluation (5-point scale) was also significantly better for the PRADA cohort than for the DIEP-PMRT cohort (4.3 [3.9-4.6] versus 3.6 [2.8-4] p=0.003). CONCLUSIONS: Aesthetic outcome for the PRADA cohort was reported to be 'good' or 'excellent' in 93% of cases using a bespoke panel assessment with robust methodology. Patient satisfaction at one year is encouraging and superior to DIEP-PMRT at 23 months. Switching surgery-radiotherapy sequencing leads to similar breast aesthetic outcomes and warrants further large-scale, multi-centre evaluation in a randomised trial..

BACKGROUND: De-escalation of axillary surgery for lymph node (LN) positive breast cancer is facilitated by marking involved nodes which, when removed with sentinel nodes constitute risk-adapted targeted axillary dissection (TAD). Whether after chemotherapy or for primary surgery, selected patients with biopsy-proven involvement of nodes may be eligible for axillary conservation. Likewise, impalpable recurrence or stage 4 patients with localised axillary disease may benefit. In these contexts, several devices are used to mark biopsied nodes to facilitate their accurate surgical removal. We report our experience using the paramagnetic MAGSEED (Endomag®, Cambridge, UK). METHODS: Local approval (BR2021_149) was obtained to interrogate a prospective database of all axillary markers. The primary endpoint was successful removal of the marked LN. RESULTS: Of 241 markers (in 221 patients) inserted between October 2018 and July 2022, all were retrieved. Of 74 patients who had Magseeds® inserted after completion of NACT (involved nodes initially marked using an UltraCor™Twirl™ marker), the Magseeds® were found outside the node in neighbouring axillary tissue in 18 (24.3%) patients. When Magseeds® were placed at commencement of NACT in 54 patients, in only 1 (1.8%) was the marker found outside the node - a statistically significantly lower rate (Chi2 10.7581 p = 0.001038). For 'primary TAD' patients and those localised for recurrent or stage IV disease, all 93 had the Magseed® found within the biopsied node. CONCLUSION: This series supports our axillary nodal marking technique as safe and reliable. For TAD following NACT, placement at the start of treatment led to a significantly higher localisation rate..

BACKGROUND: Breast Cancer incidence in the UK is estimated to rise to 71,000 per year by 2035. Preventative strategies could significantly reduce this. Preventative therapy reduces women's risk of oestrogen receptor positive breast cancer, but uptake remains low. Having established a preventative therapy clinic as part of a wider breast cancer prevention project, we explored qualitative data to inform future preventative efforts. METHOD: Women aged 30 to 60 who had benign diagnoses at a symptomatic breast clinic or were under mammographic surveillance in the moderate risk family history clinic were invited to participate in the study. Those who expressed an interest and completed an initial questionnaire had their breast cancer risk calculated using the IBIS risk calculator. Those at increased risk were invited to a consultation about preventative therapy. RESULTS: 182 women were identified as increased risk (≥ 17% lifetime or ≥ 3% 10-year risk NICE guidelines: Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer, 20131) of whom 91 women (50%) would not have been identified by family history criteria alone. 96% attended a risk/prevention consultation and all eligible women accepted screening mammography but only 14 (8%) women requested a preventative therapy prescription during the duration of the study. Reluctance to take medication and inconvenient time of life were common reasons for declining preventative therapy. Despite this, the majority were grateful for breast cancer risk and prevention information. CONCLUSIONS: Women at increased risk of breast cancer accept additional screening but are reluctant to take preventative therapy. This suggests that stratified screening methods using risk calculations would have high uptake. Raising awareness of preventative therapy is important and the breast cancer community has yet to find the optimum timing and formula for discussing it and must accept women's informed preferences above artificial targets. REGISTRATION NUMBERS: The PIONEER study was granted Health Research Authority (HRA) ethical approval by the Westminster Ethics Committee. IRAS project ID 265619, ClinicalTrials.gov Identifier: NCT04574063. Recruitment began in September 2020 and was completed in October 2021..

Local chest wall perforator flaps (CWPFs) are a volume replacement technique permitting breast-conserving surgery in patients who otherwise may require a mastectomy. These flaps are based on one or more perforating arteries arising from the lateral chest wall that travel through the soft tissue and into the sub-dermal plexus to perfuse the flap. Examples include the lateral intercostal and lateral thoracic artery perforators (LICAP and LTAP, respectively). Cross-sectional imaging of perforating vessels is not routinely performed, and vessels are mapped pre- and peri-operatively using a hand-held acoustic doppler device. As many breast cancer patients undergo pre-operative MRI scanning for oncological purposes, we investigated the role of MRI in mapping the vascular anatomy to aid with the surgical planning of CWPFs. We collated data retrospectively on a cohort of breast cancer patients who underwent breast MRI as part of routine pre-operative imaging. Axial 3D high-resolution dynamic contrast-enhanced MRI sequences with multiplanar reconstructions were analysed by a consultant radiologist. The presence and calibre of lateral chest wall perforator vessels were assessed. Fifty patients were suitable for inclusion. A consistent pattern of lateral chest wall vasculature was observed. Forty-eight patients (96%) demonstrated a bilateral lateral thoracic artery (LTA) descending inferiorly along the chest wall with two-thirds of these communicating with perforating intercostal vessels. True independent LICAP vessels were identified in six patients. From our observations, lateral CWPFs are dependent on an intricate intercommunication between intercostal vessels and the LTA which in turn supply perforators to the lateral chest wall donor site..

BACKGROUND: Radiotherapy before mastectomy and autologous free-flap breast reconstruction can avoid adverse radiation effects on healthy donor tissues and delays to adjuvant radiotherapy. However, evidence for this treatment sequence is sparse. We aimed to explore the feasibility of preoperative radiotherapy followed by skin-sparing mastectomy and deep inferior epigastric perforator (DIEP) flap reconstruction in patients with breast cancer requiring mastectomy. METHODS: We conducted a prospective, non-randomised, feasibility study at two National Health Service trusts in the UK. Eligible patients were women aged older than 18 years with a laboratory diagnosis of primary breast cancer requiring mastectomy and post-mastectomy radiotherapy, who were suitable for DIEP flap reconstruction. Preoperative radiotherapy started 3-4 weeks after neoadjuvant chemotherapy and was delivered to the breast, plus regional nodes as required, at 40 Gy in 15 fractions (over 3 weeks) or 42·72 Gy in 16 fractions (over 3·2 weeks). Adverse skin radiation toxicity was assessed preoperatively using the Radiation Therapy Oncology Group toxicity grading system. Skin-sparing mastectomy and DIEP flap reconstruction were planned for 2-6 weeks after completion of preoperative radiotherapy. The primary endpoint was the proportion of open breast wounds greater than 1 cm width requiring a dressing at 4 weeks after surgery, assessed in all participants. This study is registered with ClinicalTrials.gov, NCT02771938, and is closed to recruitment. FINDINGS: Between Jan 25, 2016, and Dec 11, 2017, 33 patients were enrolled. At 4 weeks after surgery, four (12·1%, 95% CI 3·4-28·2) of 33 patients had an open breast wound greater than 1 cm. One (3%) patient had confluent moist desquamation (grade 3). There were no serious treatment-related adverse events and no treatment-related deaths. INTERPRETATION: Preoperative radiotherapy followed by skin-sparing mastectomy and immediate DIEP flap reconstruction is feasible and technically safe, with rates of breast open wounds similar to those reported with post-mastectomy radiotherapy. A randomised trial comparing preoperative radiotherapy with post-mastectomy radiotherapy is required to precisely determine and compare surgical, oncological, and breast reconstruction outcomes, including quality of life. FUNDING: Cancer Research UK, National Institute for Health Research..

AIMS: Isotope and blue dye dual localization in sentinel lymph node biopsy (SLNB) gives localization rates of over 98% and is the recommended technique. However blue dye risks a range of adverse reactions. Since 2010, for clinically node negative disease, we have only used blue dye if there is no clear isotope signal at surgery. METHODS: Electronic records of patients who underwent isotope-only SLN localization between July 2010 and April 2012 were examined. Data were collected on localization and oncological outcomes. RESULTS: 426 patients were included. Isotope-only localization rate was 97.4% (415/426). The median follow-up was 63.5 months (IQR: 60.7-70.9). Median age was 57 (IQR: 48-67). Median SLN yield was 2 (range: 1-5). Axillary recurrence rate was 1.4% with median time to recurrence of 39.3 months. In-breast recurrence, distant disease and contralateral breast cancer rates were 2.8%, 7%, and 1.9% respectively and 15 (3.5%) patients died of metastatic breast cancer. CONCLUSION: Isotope-only SLNB has a comparable localization rate to dual isotope/blue dye SLNB and can spare the risk of blue dye adverse reactions. The low axillary recurrence rate, maintained to more than 5 years, confirms that isotope-only SLNB is a feasible and safe alternative to dual blue dye/isotope localization..

Incidence of bilateral risk-reducing mastectomies (RRMs) is increasing. The aim of this study was to compare satisfaction, aesthetic and oncological outcomes in women undergoing RRM with implant-based reconstruction comparing nipple-sparing mastectomy (NSM) with skin-sparing mastectomy (SSM) (sacrificing the nipple +/− nipple reconstruction). Women who had undergone bilateral RRM between 1997 and 2016 were invited. Aesthetic outcome and nipple symmetry were evaluated using standardized anthropometric measurements. The oncological outcome was assessed at last documented follow up. Ninety-three women (186 breasts) participated, 60 (64.5%) had NSM, 33 (35.5%) SSM. Median time between surgery and participation was 98.4 months (IQR: 61.7−133.9). Of the women, 23/33 (69.7%) who had SSM underwent nipple reconstruction. Nipple projection was shorter in the reconstructed SSM group than the maintained NSM group (p < 0.001). There was no significant difference in overall symmetry (p = 0.670), satisfaction regarding nipple preservation (p = 0.257) or overall nipple satisfaction (p = 0.074). There were no diagnoses of breast cancer at a median follow up of 129 months (IQR: 65−160.6). Women who undergo nipple-sparing RRM maintain long-term nipple symmetry. Nipple projection was less maintained after nipple reconstruction. Although satisfaction with the nipples was higher in the NSM group, this did not reach statistical significance. No breast cancers developed after RRM with long-term follow up..

BACKGROUND: Guide-wire localisation remains the most commonly used technique for localisation of impalpable breast lesions in the UK. One alternative is magnetic seed localisation. We aimed to investigate patient and clinician satisfaction in two consecutive cohorts, describe re-excision and positive margin rates, and explore reasons for positive margins and the implications for localisation techniques. METHODS: A single-institution prospective service evaluation of two cohorts of consecutive cases of wire and then Magseed localisation was carried out. Data were collected on patient and clinician satisfaction, clinico-pathological findings, and causes of involved margins. T tests were used to compare continuous variables and Chi-squared test for satisfaction outcomes. RESULTS: 168 consecutive cases used wire-guided localisation (WGL) and 128 subsequent cases used Magseeds. Patients reported less anxiety between localisation and surgery in the Magseed group, and clinicians reported greater ease of use of Magseeds. There were no differences in lesion size, surgical complexity, or re-excision rate between the groups. In a subset of patients receiving standard wide local excision (i.e., excluding mammoplasties), the impact on margin involvement was investigated. There was no significant difference in radiological under-sizing or accuracy of localisation. However, specimen weight and eccentricity of the lesion were statistically significantly lower in the Magseed group. Despite this, re-excision rates were not significantly different (p = 0.4). CONCLUSIONS: This is the first large study of satisfaction with localisation and showed clinician preference for Magseed and a reduction in patient anxiety. It also demonstrated similar positive margin rates despite smaller specimen weights in the Magseed group. Magnetic seed localisation offers an acceptable clinical alternative to guide wire localisation. The impact on local service provision should also be considered..

BACKGROUND: Participation in research can be beneficial for patients and healthcare providers, but may prove demanding at patient, clinician and organizational levels. Patient representatives are supportive of online research to overcome these challenges. The aim of this pilot study was to develop an online recruitment platform and test its feasibility and acceptability while evaluating the accuracy of participant-reported data. METHODS: The online research platform was developed in a 1-day 'hackathon' with a digital design company. Women who underwent implant-based breast reconstruction in 2011-2016 were invited by letter containing the web address (URL) of the study site and their unique study number. Once online, participants learned about the study, consented, entered data on demographics, treatment received and patient-reported outcome measures (BREAST-Q™), and booked an appointment for a single hospital visit for three-dimensional surface imaging (3D-SI). Real-time process evaluation was performed. The primary endpoint was recruitment rate. RESULTS: The recruitment rate was 40 per cent. Of the 100 women, 50 logged on to the platform and 40 completed the process through to 3D-SI. The majority of discontinuations after logging on occurred between consenting and entering demographics (3 women, 6 per cent), and between completing the BREAST-Q and booking an appointment for 3D-SI using the online calendar (3 women, 6 per cent). All women completed the online BREAST-Q™ once started. Participants took a median of 23 minutes to complete the online process. Patient-reported clinical data were accurate in 12 of 13 domains compared with electronic records (95 per cent concordance). Process evaluation demonstrated acceptability. CONCLUSION: The results of this pilot demonstrate the online platform to be acceptable, feasible, and accurate for this population from a single institution. The low-burden design may enable participation from centres with less research support and participants from hard-to-reach groups or dispersed geographical locations, but with online access..

INTRODUCTION: Over half of women with surgically managed breast cancer in the UK undergo breast-conserving treatment (BCT). While photographs are shown prior to reconstructive surgery or complex oncoplastic procedures, standard practice prior to breast conservation is to simply describe the likely aesthetic changes. Patients have expressed the desire for more personalized information about likely appearance after surgery. The hypothesis was that viewing a three-dimensional (3D) simulation improves patients' confidence in knowing their likely aesthetic outcome after surgery. METHODS: A randomized, controlled trial of 117 women planning unilateral BCT was undertaken. The randomization was three-way: standard of care (verbal description alone, control group), viewing two-dimensional (2D) photographs, or viewing a 3D simulation before surgery. The primary endpoint was the comparison between groups' median answer on a visual analogue scale (VAS) for the question administered before surgery: 'How confident are you that you know how your breasts are likely to look after treatment?' RESULTS: The median VAS in the control group was 5.2 (i.q.r. 2.6-7.8); 8.0 (i.q.r. 5.7-8.7) for 2D photography, and 8.9 (i.q.r. 8.2-9.5) for 3D simulation. There was a significant difference between groups (P < 0.010) with post-hoc pairwise comparisons demonstrating a statistically significant difference between 3D simulation and both standard care and viewing 2D photographs (P < 0.010 and P = 0.012, respectively). CONCLUSION: This RCT has demonstrated that women who viewed an individualized 3D simulation of likely aesthetic outcome for BCT were more confident going into surgery than those who received standard care or who were shown 2D photographs of other women. The impact on longer-term satisfaction with outcome remains to be determined.Registration number: NCT03250260 (http://www.clinicaltrials.gov)..

INTRODUCTION: Evaluation of aesthetics after breast reconstruction is challenging. In the absence of an objective measurement, panel assessment is widely adopted. Heterogeneity of scales and poor internal consistency make comparison difficult. Development and validation of an expert panel scale using a Delphi consensus process is described. It was designed specifically for use as the gold standard for development of an objective evaluation tool using 3-Dimensional Surface Imaging (3D-SI). MATERIALS AND METHODS: 20 items relating to aesthetic assessment were identified for consideration in the Delphi consensus process. Items were selected for inclusion in the definitive panel scale by iterative rounds of voting according to importance, consensus discussion, and a final vote. The Delphi-derived scale was tested on a clinical research series for intra- and inter-panellist, and intra-panel reliability, and correlation with Patient Reported Outcome Measures (PROMs). RESULTS: 61 surgeons participated in the Delphi process. Oncoplastic and plastic surgeons were represented. The Delphi-derived scale included symmetry, volume, shape, position of breast mound, nipple position, and a global score. Intra-panellist reliability ranged from poor to almost perfect (wκ<0to0.86), inter-rater reliability was fair (ICC range 0.4-0.5) for individual items and good (ICC0.6) for the global score, intra-panel reliability was moderate to substantial (wκ0.4-0.7), and correlation with PROMs was moderate (r = 0.5p < 0.01). CONCLUSIONS: The Delphi-derived panel evaluation is at least as good as other scales in the literature and has been developed specifically to provide expert evaluation of aesthetics after breast reconstruction. The logistical constraints of panel assessment remain, reinforcing the need to develop an objective evaluation method..

BACKGROUND: Two-thirds of patients with early breast cancer undergo breast-conserving treatment (BCT). Aesthetic outcome is important and has long term implications for psychosocial wellbeing. The aesthetic goal of BCT is symmetry for which there is no gold-standard measure. Panel scoring is the most widely adopted assessment but has well-described limitations. This paper describes a model to objectively report aesthetic outcome using measures derived from 3-dimensional surface images (3D-SI). METHOD: Objective measures and panel assessment were undertaken independently for 3D-SI of women who underwent BCT 1-5 years previously. Univariate analysis was used to test for association between measures and panel score. A forward stepwise multiple linear regression model was fitted to identify 3D measurements that jointly predicted the mean panel score. The fitted model coefficients were used to predict mean panel scores for an independent validation set then compared to the mean observed panel score. RESULTS: Very good intra-panel reliability was observed for the training and validation sets (wκ = 0.87, wκ = 0.84). Six 3D-measures were used in the multivariate model. There was a good correlation between the predicted and mean observed panel score in the training (n = 190) and validation (n = 100) sets (r = 0.68, r = 0.65). The 3D model tended to predict scores towards the median. The model was calibrated which improved the distribution of predicted scores. CONCLUSION: A six-variable objective aesthetic outcome model for BCT has been described and validated. This can predict and could replace panel assessment, facilitating the independent and unbiased evaluation of aesthetic outcome to communicate and compare results, benchmark practice, and raise standards..

BACKGROUND: Use of biological or synthetic mesh might improve outcomes of immediate implant-based breast reconstruction-breast reconstruction with implants or expanders at the time of mastectomy-but there is a lack of high-quality evidence to support the safety or effectiveness of the technique. We aimed to establish the short-term safety of immediate implant-based breast reconstruction performed with and without mesh, to inform the feasibility of undertaking a future randomised clinical trial comparing different breast reconstruction techniques. METHODS: In this prospective, multicentre cohort study, we consecutively recruited women aged 16 years or older who had any type of immediate implant-based breast reconstruction for malignancy or risk reduction, with any technique, at 81 participating breast and plastic surgical units in the UK. Data about patient demographics and operative, oncological, and complication details were collected before and after surgery. Outcomes of interest were implant loss (defined as unplanned removal of the expander or implant), infection requiring treatment with antibiotics or surgery, unplanned return to theatre, and unplanned re-admission to hospital for complications of reconstructive surgery, up to 3 months after reconstruction and assessed by clinical review or patient self-report. Follow-up is complete. The study is registered with the ISRCTN Registry, number ISRCTN37664281. FINDINGS: Between Feb 1, 2014, and June 30, 2016, 2108 patients had 2655 mastectomies with immediate implant-based breast reconstruction at 81 units across the UK. 1650 (78%) patients had planned single-stage reconstructions (including 12 patients who had a different technique per breast). 1376 (65%) patients had reconstruction with biological (1133 [54%]) or synthetic (243 [12%]) mesh, 181 (9%) had non-mesh submuscular or subfascial implants, 440 (21%) had dermal sling implants, 42 (2%) had pre-pectoral implants, and 79 (4%) had other or a combination of implants. 3-month outcome data were available for 2081 (99%) patients. Of these patients, 182 (9%, 95% CI 8-10) experienced implant loss, 372 (18%, 16-20) required re-admission to hospital, and 370 (18%, 16-20) required return to theatre for complications within 3 months of their initial surgery. 522 (25%, 95% CI 23-27) patients required treatment for an infection. The rates of all of these complications are higher than those in the National Quality Standards (<5% for re-operation, re-admission, and implant loss, and <10% for infection). INTERPRETATION: Complications after immediate implant-based breast reconstruction are higher than recommended by national standards. A randomised clinical trial is needed to establish the optimal approach to immediate implant-based breast reconstruction. FUNDING: National Institute for Health Research, Association of Breast Surgery, and British Association of Plastic, Reconstructive and Aesthetic Surgeons..

BACKGROUND: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. METHODS: Consecutive women undergoing mastectomy ± IBR for breast cancer July-December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. RESULTS: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. CONCLUSIONS: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients..

BACKGROUND: The use of nipple-sparing mastectomy (NSM) is increasing, despite unproven oncological safety in the therapeutic setting. The aim of this systematic review was to determine the safety and efficacy of NSM compared with skin-sparing mastectomy (SSM). METHODS: A literature search of all original studies including RCTs, cohort studies and case-control studies comparing women undergoing therapeutic NSM or SSM for breast cancer was undertaken. Primary outcomes were oncological outcomes; secondary outcomes were clinical, aesthetic, patient-reported and quality-of-life outcomes. Data analysis was undertaken to explore the relationship between NSM and SSM, and preselected outcomes. Heterogeneity was assessed using the Cochrane tests. RESULTS: A total of 690 articles were identified, of which 14 were included. There was no statistically significant difference in 5-year disease-free survival and mortality for NSM and SSM groups, where data were available. Local recurrence rates were also similar for NSM and SSM (3·9 versus 3·3 per cent respectively; P = 0·45). NSM had a partial or complete nipple necrosis rate of 15·0 per cent, and a higher complication rate than SSM (22·6 versus 14·0 per cent respectively). The higher overall complication rate was due to the rate of nipple necrosis in the NSM group (15·0 per cent). CONCLUSION: In carefully selected cases, NSM is a viable choice for women with breast cancer who need to have a mastectomy. More research is needed to help further refine which surgical approaches to NSM optimize outcomes..

Purpose: The most significant prognostic factor in early breast cancer is lymph node involvement. This stage between localized and systemic disease is key to understanding breast cancer progression; however, our knowledge of the evolution of lymph node malignant invasion remains limited, as most currently available data are derived from primary tumors.Experimental Design: In 11 patients with treatment-naïve node-positive early breast cancer without clinical evidence of distant metastasis, we investigated lymph node evolution using spatial multiregion sequencing (n = 78 samples) of primary and lymph node deposits and genomic profiling of matched longitudinal circulating tumor DNA (ctDNA).Results: Linear evolution from primary to lymph node was rare (1/11), whereas the majority of cases displayed either early divergence between primary and nodes (4/11) or no detectable divergence (6/11), where both primary and nodal cells belonged to a single recent expansion of a metastatic clone. Divergence of metastatic subclones was driven in part by APOBEC. Longitudinal ctDNA samples from 2 of 7 subjects with evaluable plasma taken perioperatively reflected the two major evolutionary patterns and demonstrate that private mutations can be detected even from early metastatic nodal deposits. Moreover, node removal resulted in disappearance of private lymph node mutations in ctDNA.Conclusions: This study sheds new light on a crucial evolutionary step in the natural history of breast cancer, demonstrating early establishment of axillary lymph node metastasis in a substantial proportion of patients. Clin Cancer Res; 24(19); 4763-70. ©2018 AACR..

Nipple-sparing mastectomy is a valuable addition to the options available for women at high risk of developing breast cancer. In this review, we summarize current knowledge about the high-risk genes, BRCA1, BRCA2 and TP53 and the associated guidelines with regard to risk-reducing surgery. We consider other genetic risks and high-risk lesions. We discuss the literature on bilateral mastectomy for breast cancer risk-reduction, and the results of nipple-sparing mastectomy in particular. Finally, we report on patient satisfaction with these procedures and the impact that nipple-sparing mastectomy may have on women at high-risk of breast cancer..

PURPOSE: Three-dimensional surface imaging (3D-SI) of the breasts enables the measurement of breast volume and shape symmetry. If these measurements were sufficiently accurate and repeatable, they could be used in planning oncological breast surgery and as an objective measure of aesthetic outcome. The aim of this study was to validate the measurements of breast volume and symmetry provided by the Vectra XT imaging system. METHODS: To validate measurements, breast phantom models of true volume between 100 and 1000 cm3 were constructed and varying amounts removed to mimic breast tissue 'resections'. The volumes of the phantoms were measured using 3D-SI by two observers and compared to a gold standard. For intra-observer repeatability and inter-observer reproducibility in vivo, 16 patients who had undergone oncological breast surgery had breast volume and symmetry measured three times by two observers. RESULTS: A mean relative difference of 2.17 and 2.28% for observer 1 and 2 respectively was seen in the phantom measurements compared to the gold standard (n = 45, Bland Altman agreement). Intra-observer variation over ten repeated measurements demonstrated mean coefficients of variation (CV) of 0.58 and 0.49%, respectively. The inter-observer variation demonstrated a mean relative difference of 0.11% between the two observers. In patients, intra-observer variation over three repeated volume measurements for each observer was 3.9 and 3.8% (mean CV); the mean relative difference between observers was 5.78%. For three repeated shape symmetry measurements using RMS projection difference between the two breasts, the intra-observer variations were 8 and 14% (mean CV), the mean relative difference between observers was 0.43 mm for average symmetry values that ranged from about 3.5 to 15.5 mm. CONCLUSION: This first validation of breast volume and shape symmetry measurements using the Vectra XT 3D-SI system suggests that these measurements have the potential to assist in pre-operative planning and also as a measure of aesthetic outcome..

BACKGROUND: The authors investigated aesthetic outcome and patient satisfaction in women who have undergone deep inferior epigastric artery perforator (DIEP) flap reconstruction in the setting of postmastectomy radiotherapy. Patients who underwent DIEP flap reconstruction without postmastectomy radiotherapy were the control group. METHODS: Participants who had undergone DIEP flap reconstruction between September 1, 2009, and September 1, 2014, were recruited, answered the BREAST-Q, and underwent three-dimensional surface-imaging. A panel assessed the aesthetic outcome by reviewing these images. RESULTS: One hundred sixty-seven women participated. Eighty women (48 percent) underwent immediate DIEP flap reconstruction and no postmastectomy radiotherapy; 28 (17 percent) underwent immediate DIEP flap reconstruction with postmastectomy radiotherapy; 38 (23 percent) underwent simple mastectomy, postmastectomy radiotherapy, and DIEP flap reconstruction; and 21 (13 percent) underwent mastectomy with temporizing implant, postmastectomy radiotherapy, and DIEP flap reconstruction. Median satisfaction scores were significantly different among the groups (p < 0.05). Post hoc comparison demonstrated that women who had an immediate DIEP flap reconstruction were significantly less satisfied if they had postmastectomy radiotherapy. In women requiring radiotherapy, those undergoing delayed reconstruction after a simple mastectomy were most satisfied, but there was no significant difference between the immediate DIEP flap and temporizing implant groups. Median panel scores differed among groups, being significantly higher if the immediate reconstruction was not subjected to radiotherapy. There was no significant difference in panel assessment among the three groups of women who had received radiotherapy. CONCLUSIONS: Patients who avoid having their immediate DIEP flap reconstruction irradiated are more satisfied and have better aesthetic outcome than those who undergo postmastectomy radiotherapy. In women requiring radiotherapy and who wish to have an immediate or "delayed-immediate" reconstruction, there were no significant differences in panel or patient satisfaction. Therefore, immediate DIEP flap reconstruction or mastectomy with temporizing implant then DIEP flap surgery are acceptable treatment pathways in the context of post-mastectomy radiotherapy..

INTRODUCTION: Bilateral mammoplasty (BM) can optimise oncological safety and aesthetic outcomes in women with large or ptotic breasts whose tumour to breast volume ratio or tumour location pose a challenge to standard breast-conserving therapy (BCT) and for whom mastectomy (with or without reconstruction) may be the only alternative. METHODS: We undertook a comprehensive analysis of surgical outcomes (complications according to the Clavien Dindo classification), acute radiation morbidity (Radiation Therapy Oncology Group classification), oncological outcomes, and patient satisfaction (BREAST-Q questionnaire) in women who underwent BM for breast cancer (BC) from June 2009-November 2014. RESULTS: 168 women were included. Median age was 55 years (range:33-84) and median tumour size at imaging 35 mm (range:0-170). Median specimen weight was 242 g (range 39-1824). The wise pattern technique was used in 87.5% of procedures. At least one complication occurred in 68 (40.5%) women, mostly Clavien Dindo grade 1. Grade 3 complications were infrequent (8.9%) but occurred mainly on the therapeutic mammoplasty (TM) side (p < 0.05). Complications were associated with higher BMI, specimen weight and longer time to radiotherapy (p < 0.05). Median follow-up was 37 months (range: 13-77). Local recurrence occurred in 3 (1.8%), distant metastases in 5 (3.0%), and 10 (6.0%) women have died. The median score for 'satisfaction with breasts' was 77 (range: 0-100). CONCLUSIONS: This study provides concurrent data on surgical, oncological and patient-reported outcomes. It offers evidence that BM is an effective treatment for breast cancer in large- or ptotic-breasted women..

INTRODUCTION: Oncoplastic breast surgery is used to extend the role of breast-conserving surgery (BCS) to women with an unfavourable tumour to breast volume ratio. However, large-breasted women with a relatively small breast cancer may be offered bilateral reduction mammoplasty (BRM) despite being suitable for standard BCS as the more complex surgery may have advantages in terms of patient satisfaction and reduced adverse effects of radiotherapy. PATIENT AND METHODS: This retrospective study evaluated surgical and patient-reported outcome measures (PROMs) in large-breasted women with early (<3 cm) breast cancer, who have undergone unilateral standard BCS or BRM. RESULTS: This series included 157 women, 87 in the unilateral BCS group and 70 in the BRM group. Median age was 60.2 years (range: 33-83.9). Median follow-up was 36 months (range: 9.8-76). Tumour size, rates of axillary dissection, adjuvant chemotherapy and tumour bed irradiation boost were significantly greater in the BRM group (p < 0.05). The surgical complication rate was not significantly different (43.7% vs. 34.3%, p = 0.253). Re-excision rates were higher in the standard BCS group (p < 0.05). Time to chemotherapy was similar, but time to radiotherapy was longer after BRM surgery (p = 0.025). Despite worse prognostic factors, more complex surgery and more aggressive adjuvant treatment, patients report better satisfaction and physical functioning and fewer adverse effects of radiotherapy after BRM than standard unilateral BCS. This difference was not statistically different in this small study (p > 0.05). CONCLUSION: Limitations of this study mean it can only be regarded as hypothesis-generating. Nonetheless, the trends merit a prospective study to investigate the optimal management of smaller breast cancers in larger-breasted women..

PURPOSE: To establish whether objective measurements of symmetry of volume and shape using three-dimensional surface imaging (3D-SI) can be used as surrogate markers of aesthetic outcome in patients who have undergone breast conserving therapy (BCT). METHODS: Women who had undergone unilateral BCT in the preceding 1-6 years were invited to participate. Participants completed a satisfaction questionnaire (BREAST-Q) and underwent 3D-SI. Volume and surface symmetry were measured on the images. Assessment of aesthetic outcome was undertaken by a panel of clinicians. The Kruskal-Wallis test was used to assess the relationship between volume and shape symmetry measurements with the panel score. Spearman's rho correlations were used to assess the relationship between the measurements and patient satisfaction. RESULTS: 200 women participated. Median volume symmetry was 87% (IQR 78-93) and shape symmetry was 5.9 mm (IQR 4.2-8.0). The participants were grouped according to panel assessment of aesthetic outcome (poor, fair, good, excellent) and the median volume and shape symmetry was calculated for each group. Volume symmetry significantly differed between the groups. Post hoc pairwise comparisons demonstrated that these differences existed between panel scores of fair versus good and good versus excellent. Median shape symmetry also differed according to patient panel groups with four significant pairwise comparisons between poor versus good, poor versus excellent, fair versus good and fair versus excellent. There was a significant but weak correlation of both volume symmetry and surface asymmetry with BREAST-Q scores (correlation coefficients 0.187 and -0.229, respectively). CONCLUSION: Breast volume and shape symmetry are both associated with panel assessment scores and patient satisfaction. The objective volume and shape symmetry measures were strongly associated with panel assessment scores, such that a 3D-SI tool could replace panel assessment as a faster and more objective method of evaluating aesthetic outcomes..

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INTRODUCTION: Ultrasound (US) is the imaging modality of choice for staging the axilla prior to surgery in patients with breast cancer (BC). High pathological complete response rates in the axilla after NACT mean a more conservative approach to surgery can be considered. Radiological re-staging is important in this decision making. After the presentation of results from ACOSOG Z1071 in December 2012, formal ultrasound re-assessment of the axilla after primary therapy was specifically requested in our institution. We report on the accuracy of axillary US (aUS) for identifying residual axillary disease post-NACT. METHODS: Data were collected on patients who had proven axillary disease prior to NACT and underwent axillary lymph node dissection after NACT between January 2013 and December 2015. Post-chemotherapy aUS reports and axillary pathology reports were classified as positive or negative for abnormal lymph nodes and for residual disease (cCR and pCR respectively). RESULTS: The sensitivity and specificity of aUS was 71% and 88% respectively. The negative predictive value (NPV) was 83%. The false negative rate was 29%. CONCLUSIONS: Axillary ultrasound provides clinically useful information post-NACT, which will guide surgical decision-making. Patients with aUS-negative axillae are likely to have a lower false negative rate of SLNB after NACT (Boughey et al.). However, aUS does not replace the need to identify and biopsy the nodes which were proven to be positive prior to NACT..

BACKGROUND: Traditionally axillary surgery has been used to provide staging information and until recently was thought to improve loco-regional control. However, a more minimal approach to the axilla is now being adopted. The aim of this study was to assess long term outcomes of patients with 'low-risk' breast cancers who did not undergo any axillary surgery. 'Low-risk' criteria were: postmenopausal, <20 mm grade 1 or <15 mm grade 2, LVI-ve, ER +ve. METHODS: Women with invasive breast cancer that did not undergo any axillary surgery were identified. Patients were censored when an event or death occurred or at last follow-up at breast clinic or with their General Practitioner. RESULTS: Between 05/01/1995-20/11/2006, 194 patients (199 tumours) were operated upon without axillary surgery. Median follow-up was 10.4 years. 128 patients met low-risk criteria and 71 did not (patient choice = 42, medical fitness = 29). In the 'low risk' cohort there were two axillary recurrences, with a cumulative incidence of 0.8% and 1.9% at 5 and 10 years respectively. DDFS was 99.2% (94.1-99.9%), and 97% (90.0-99%) at 5 and 10 years respectively and DFS was 96.6% (91.1-98.7%) and 91.2% (82.6-95.6%). OS was 90.3% (95% CI: 83.6-94.4) and 75.5% (95% CI: 65.9-82.8) at 5 and 10 years respectively. CONCLUSION: Axillary recurrence and DDFS in this low-risk cohort is favourable. In the modern era of breast cancer management it is possible to define a group of women in whom axillary surgery can be omitted..

PURPOSE: The most recently developed module of the BREAST-Q, a validated patient outcome measure, is for patients who have undergone breast-conserving therapy (BCT) for cancer. This aim of this study was to assess patient satisfaction and quality of life after BCT using BREAST-Q, investigate clinical risk factors for lower satisfaction and explore the relationship between patient satisfaction with the appearance of their breasts and the other domains of the BREAST-Q. METHODS: Women who had undergone unilateral BCT in the preceding 1-6 years were invited to participate at the time of their annual surveillance mammogram. Clinicopathological data were collected from an electronic database. Linear regression was used to evaluate risk factors for lower satisfaction. Spearman's rho correlation coefficients were calculated to evaluate the relationship between domains. RESULTS: 200 women completed the questionnaire. Mean age was 60 years (SD 11.1). Time from surgery was 35.5 months (SD 17.8). Median score for 'Satisfaction with breasts' was 68 (interquartile range 55-80). Lowest scores were for 'sexual wellbeing' (57, IQR 45-66). On multivariate analysis, BMI at the time of surgery (p = 0.002), delayed wound healing (p = 0.001) and axillary surgery (p = 0.003) were independent risk factors for lower satisfaction. There was significant correlation between 'Satisfaction with breasts' and all other BREAST-Q domains. CONCLUSION: High BMI, delayed wound healing and axillary surgery are risk factors for lower patient satisfaction. This first publication reporting the whole dataset for the BREAST-Q BCT will serve as a benchmark for future studies of patient satisfaction following BCT..

INTRODUCTION: Breast cancer has a lifetime incidence of one in eight women. Over the past three decades there has been a move towards breast conservation and a focus on aesthetic outcomes while maintaining oncological safety. For some patients, mastectomy is the preferred option. There is growing interest in the potential use of nipple sparing mastectomy (NSM). However, oncological safety remains unproven, and the benefits and indications have not been clearly identified. The objective of this systematic review will be to determine the safety and efficacy of NSM as compared with skin sparing mastectomy (SSM). METHODS AND ANALYSIS: All original comparative studies including; randomised controlled trials, cohort studies and case-control studies involving women undergoing either NSM or SSM for breast cancer will be included. Outcomes are primary-relating to oncological outcomes and secondary-relating to clinical, aesthetic, patient reported and quality of life outcomes. A comprehensive electronic literature search, designed by a search specialist, will be undertaken. Grey literature searches will also be conducted. Eligibility assessment will occur in two stages; title and abstract screening and then full text assessment. Each step will be conducted by two trained teams acting independently. Data will then be extracted and stored in a database with standardised extraction fields to facilitate easy and consistent data entry. Data analysis will be undertaken to explore the relationship between NSM or SSM and preselected outcomes, heterogeneity will be assessed using the Cochrane tests. ETHICS AND DISSEMINATION: This systematic review requires no ethical approval. It will be published in a peer-reviewed journal. It will also be presented at national and international conferences. Updates of the review will be conducted to inform and guide healthcare practice and policy..

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INTRODUCTION: Doctors who are diagnosed with breast cancer form a small subset of women with unique insight into their disease. The aim of this study was to compare key treatment decisions in medically-qualified doctors with equivalent degree-educated, matched controls diagnosed with early breast cancer. METHODS: Patients diagnosed with breast cancer between 01/01/2006 and 31/12/2011 were included and screened for occupation by 2 independent investigators. Allied health professionals with a medical background (e.g. nurses, physiotherapists) were excluded. Patient controls were matched by age, nodal status and grade. If there were more than 5 possible matches then those patients with the closest tumour size were selected. RESULTS: 5259 of 8623 patients had signed the generic research consent form. 619 of these were either doctors, or had received tertiary level education and could form appropriate controls. After exclusions, 46 medically-qualified doctors and 230 matched control patients were included in the analysis. No statistical differences in age or tumour characteristics were identified between doctors with breast cancer and matched controls. No differences were identified between the two groups in the uptake of mastectomy, chemotherapy, immediate breast reconstruction or post-mastectomy radiotherapy. CONCLUSION: Medically-qualified patients diagnosed with early breast cancer are no more likely to opt for mastectomy, chemotherapy, immediate breast reconstruction or post-mastectomy radiotherapy than non-medically-qualified controls. The level of information generally provided to patients with breast cancer is adequate for a similar decision to be made by control patients with equivalent levels of education, independent of any knowledge of pathology or understanding of the medical system that medically-qualified patients may possess..

Three-dimensional surface imaging (3D-SI) is being marketed as a tool in aesthetic breast surgery. It has recently also been studied in the objective evaluation of cosmetic outcome of oncological procedures. The aim of this review is to summarise the use of 3D-SI in oncoplastic, reconstructive and aesthetic breast surgery. An extensive literature review was undertaken to identify published studies. Two reviewers independently screened all abstracts and selected relevant articles using specific inclusion criteria. Seventy two articles relating to 3D-SI for breast surgery were identified. These covered endpoints such as image acquisition, calculations and data obtainable, comparison of 3D and 2D imaging and clinical research applications of 3D-SI. The literature provides a favourable view of 3D-SI. However, evidence of its superiority over current methods of clinical decision making, surgical planning, communication and evaluation of outcome is required before it can be accepted into mainstream practice..

INTRODUCTION: Action On Plastic Surgery (AOPS) criteria for funding of gynaecomastia surgery are: the patient should be post-pubertal, have a BMI ≤ 25 kg/m(2), endocrine and drug causes and breast cancer should be excluded and the patient should demonstrate psychological distress. We evaluated how NHS funding for gynaecomastia surgery varies between Clinical Commissioning Groups (CCGs) in England and whether there is a "postcode lottery". METHODS: The gynaecomastia surgery policies for 211 CCGs in NHS England were reviewed against the AOPS criteria and grouped according to their funding policies: group 1 (if criteria met, funding approved); group 2, (if criteria met, prior approval required); group 3 (no criteria, individual funding request only) and group 4 (no funding). RESULTS: Policies were available for all CCGs. Fifty-nine (28.0%) CCGs were in group 1, 87 (41.2%) in group 2, 44 (20.9%) in group 3 and 21 (10.0%) in group 4. Of those in groups 1 and 2, five (3.4%) CCGs used all six AOPS criteria. Approximately 70% CCGs with criteria (in groups 1 and 2) stipulated that the patient should be post-pubertal, have a BMI ≤ 25 kg/m(2) and endocrine and drug causes should be excluded. Breast cancer should be excluded in 51.4% and the patient should show psychological distress in 13.7% CCGs. Of those in groups 1 and 2, 118 (80.8%) CCGs specified additional criteria. CONCLUSIONS: CCGs do not use the AOPS criteria uniformly and restrict surgery according to their own criteria. Overall, there is a "postcode lottery" for gynaecomastia surgery within NHS England..

Knowledge of the anatomy of the nipple and breast skin is fundamental to any surgeon practicing conservative mastectomies. In this paper, the relevant clinical anatomy will be described, mainly focusing on the anatomy of the "oncoplastic plane", the ducts and the vasculature. We will also cover more briefly the nerve supply and the arrangement of smooth muscle of the nipple. Finally the lymphatic drainage of the nipple and areola will be described. An appreciation of the relevant anatomy, together with meticulous surgical technique may minimise local recurrence and ischaemic complications..

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BACKGROUND: There is a limited evidence base to guide surgeons on the ideal thickness of skin flaps during mastectomy. Here the literature relevant to optimizing mastectomy skin flap thickness is reviewed, including anatomical studies, oncological considerations, factors affecting viability, and the impact of surgical technique and adjuvant therapies. METHODS: A MEDLINE search was performed using the search terms 'mastectomy' and 'skin flap' or 'flap thickness'. Titles and abstracts from peer-reviewed publications were screened for relevance. RESULTS: A subcutaneous layer of variable thickness that contains minimal breast epithelium lies between the dermis and breast tissue. The thickness of this layer may vary within and between breasts, and does not appear to be associated with obesity or age. The existence of a distinct layer of superficial fascia in the breast remains controversial and may be present in only up to 56 per cent of patients. When present, it may not be visible macroscopically, and can contain islands of breast tissue. As skin flap necrosis occurs in approximately 5 per cent of patients, a balance must be sought between removing all breast tissue at mastectomy and leaving reliably viable skin flaps. CONCLUSION: The variable and unpredictable thickness of the breast subcutaneous layer means that a single specific universal thickness for mastectomy skin flaps cannot be recommended. It may be that the plane between the subdermal fat and breast parenchyma is a reasonable guide for mastectomy flap thickness, but this may not always correspond to a subcutaneous fascial layer..

BACKGROUND: Advanced locoregional therapies continue to advance the treatment of breast cancer. These techniques are geared towards optimizing oncologic and aesthetic outcome as well as decreasing and treating morbidity. We present a selection of specialized locoregional therapies dedicated to the optimization of breast cancer treatment. METHODS: Locoregional therapies for breast cancer are presented to address breast conservation techniques, lipofilling techniques, reconstruction techniques for nipple-sparing mastectomy, re-irradiating the breast, axillary reverse mapping, and vascularized lymph node transfer. RESULTS: We present a synopsis of identified breast locoregional therapies targeted to address optimal oncologic and aesthetic outcome as well as decrease and treat morbidity..

The rate of surgical site infection (SSI) after breast surgery is higher than expected for a 'clean procedure'. There is currently no consensus on the use of antibiotics, and as a result there is variation in use. An infection may compromise cosmesis and delay the start of adjuvant therapy. This research highlight reviews a recent paper by Gulluoglu and colleagues investigating the use of antibiotics in overweight and obese patients undergoing breast cancer surgery and also reviews the current literature on this important topic..

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BACKGROUND: The utility of axillary lymph node dissection (ALND) in the management of breast cancer is currently under close scrutiny. At primary diagnosis the use of sentinel lymph node biopsy (SLNB) has restricted ALND for proven nodal disease, however the management of the axilla at local (in-breast) relapse is less clearly defined with many undergoing routine ALND. This review examines the role of SLNB in the re-operative setting with the objective of developing an axillary management algorithm for use at in-breast local relapse, and restricting ALND to node-positive recurrent cancers. METHODS: We reviewed published reports of SLNB at local relapse in women who had previously undergone axillary surgery either as lymph node biopsy, SLNB, axillary sampling (AS) or axillary lymph node dissection (ALND). RESULTS: There have been no randomised trials. Six reports with 327 cases were identified; of which 61% (199/327) had previous SLNB or ALND with <9 nodes removed. There was an overall successful sentinel lymph node (SLN) localisation at re-operation of 69% (227/327), range of 51-100%. In patients who have previously had limited axillary surgery (<9 nodes removed), the rate of successful SLN localisation was 83% (165/199), range of 68-100% and 142/165 (86%, range 80-100%) were node negative. In these highly selected patients no axillary recurrences were noted in those who had a negative SLN at re-operation after 26-46 months follow up. CONCLUSION: SLNB at in-breast relapse is feasible and safe with successful localisation related to the extent of previous axillary surgery..

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AIMS: Axillary nodal status is the most important prognostic indicator which in turn influences adjuvant therapy and long term outcomes. The aim of this study was to compare total nodal yields from primary axillary lymph node dissection (pALND) with completion ALND after a cancer positive SLNB: either concurrently (cALND) following intra-operative assessment (IOA) of the SLN's or as a delayed procedure (dALND) when the SLN was found to be cancer positive on post-operative histological examination. METHODS: All axillary procedures performed between May 2006 and September 2009 were identified from a prospective database and categorised into four groups: SLNB with no further axillary surgery, pALND, cALND and dALND. Total nodal yield was the sum of SLN/s and ALND yields. RESULTS: Of 1025 axillary procedures, ALND accounted for 332 (32.4%) of which 207 (62.3%) underwent pALND, 43 (12.9%) cALND, and 82 (24.6%) dALND. Median nodal yields were 15.0, 16.0 and 14.5 respectively (p = 0.3). CONCLUSION: Total nodal yields for primary, concurrent and delayed ALND were comparable suggesting completion dALND performed as a second operation does not compromise axillary staging..

Although there is scant evidence to support multidisciplinary meetings in any cancer specialty, they are now regarded as best practice. We believe the oncoplastic multidisciplinary meeting plays a similarly important role, consolidating oncoplastic multidisciplinary working and allowing transparent decision making, standardisation of care and recording of results. This may drive oncoplastic surgery to an evidence-based position from which oncoplastic excellence can be achieved..

BACKGROUND: Although effective local control is the primary goal of surgery for breast cancer, the long-term aesthetic outcome is also important. Nipple-sparing mastectomy aims to address this, but there is no consensus on its clinical application. Evidence relating to oncological safety, surgical technique and early data on aesthetic outcome was reviewed. METHODS: The review was based on a PubMed search using the terms 'nipple-sparing' or 'subcutaneous mastectomy' and 'breast cancer'. RESULTS: Large pathological studies report occult nipple involvement with cancer in 5.6-31 per cent, reflecting variation in inclusion criteria. Recent clinical series with careful patient selection report local recurrence in less than 5 per cent of patients. The incidence of cancer in the retained nipple after risk-reducing mastectomy is less than 1 per cent. Nipple necrosis rates range up to 8 and 16 per cent for total and partial necrosis respectively. Variations in outcome result from differences in extent of resection, placement of incisions and type of breast reconstruction. CONCLUSION: Nipple-sparing mastectomy is an acceptable technique for women undergoing risk-reducing mastectomy. In the therapeutic setting, it may be offered to patients with smaller tumours far from the nipple and favourable pathological features. Women should be counselled about nipple necrosis and the potential for local recurrence..

INTRODUCTION: Immediate breast reconstruction after mastectomy has known psychological and financial advantages but it is difficult to compare the outcome of various methods of reconstruction. Re-operation rates are an objective measure of surgical intervention required to attain and maintain acceptable cosmesis. PATIENTS AND METHODS: A series of 95 patients (110 immediate reconstructions) was analysed for number of re-operations required within 5 years of initial surgery, magnitude of procedures, 'survival' of the reconstruction and effect of radiotherapy. RESULTS: Although more intervention was seen in patients with implant-based reconstruction and the time-course over which autologous and implant-based reconstructions fail is different these did not reach statistical significance. Radiotherapy has a significant effect on failure of implant-based reconstruction. CONCLUSIONS: Long-term, large studies of immediate reconstruction are required to assess adequately the impact of type of reconstruction on re-operation rates. The National Mastectomy and Breast Reconstruction Audit is ideally placed to provide answers to remaining questions about longevity of immediate breast reconstruction and the effect that late failure has on patient satisfaction..

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BACKGROUND: Breast conservation is possible in breast cancer patients whose mammographic lesions are large enough to require multiple localizing wires for excision. METHODS: A retrospective review of 112 patients who underwent multiple-wire and 160 controls who underwent single-wire lumpectomy for breast cancer. Rates of in-breast recurrence, metastasis, and additional imaging and biopsy procedures were calculated. RESULTS: The median follow-up was 24 months. One multiple-wire and 2 single-wire patients developed in-breast recurrences (P = .84). No distant metastases developed among the multiple-wire patients. Additional follow-up imaging was obtained in 29% of multiple-wire and 22% of single-wire cases (P = .1). Seven (6%) of the multiple-wire and 11 (6%) of the single-wire cases underwent biopsy (P = .94). CONCLUSIONS: We found no increased risk of early local recurrence, metastasis, or additional imaging or biopsies in patients requiring multiple-wire localization for lumpectomy. Breast conservation should be considered a safe option even for patients with mammographically extensive lesions..

PURPOSE: Although breast-conserving surgery is a standard approach for patients with breast cancer, mastectomy often becomes necessary. Surgical options now include nipple-sparing mastectomy but its oncological safety is still controversial. This study evaluates frequency and patterns of occult nipple involvement in a large contemporary cohort of patients with the retroareolar margin as possible indicator of nipple involvement. PATIENTS AND METHODS: Three hundred sixteen consecutive mastectomy specimens (232 therapeutic, 84 prophylactic) with grossly unremarkable nipples were evaluated by coronal sections through the entire nipple and subareolar tissue. Extent and location of nipple involvement by carcinoma was assessed with the tissue deep to the skin as potential retroareolar en-face resection margin. RESULTS: Seventy-one percent of nipples from therapeutic mastectomies showed no pathologic abnormality, 21% had ductal carcinoma in situ (DCIS), invasive carcinoma (IC), or lymphovascular invasion (LVI), and 8% lobular neoplasia (lobular carcinoma in situ). Human epidermal growth factor receptor 2 amplification, tumor size, and tumor-nipple distance were associated with nipple involvement by multivariate analysis (P = .0047, .0126, and .0176); histologic grade of both DCIS (P = .002) and IC (P = .03), LVI (P = .03), and lymph node involvement (P = .02) by univariate analysis. Nipple involvement by IC or DCIS was identified in the retroareolar margin with a sensitivity of 0.8 and a negative predictive value of 0.96. None of the 84 prophylactic mastectomies showed nipple involvement by IC or DCIS. CONCLUSION: Nipple-sparing mastectomy may be suitable for selected cases of breast carcinoma with low probability of nipple involvement by carcinoma and prophylactic procedures. A retroareolar en-face margin may be used to test for occult involvement in patients undergoing nipple-sparing mastectomy..

BACKGROUND: This prospective study aimed to build a predictive model using preoperative information to aid selection for nipple-sparing mastectomy. METHODS: Two hundred consecutive skin-sparing mastectomy specimens without overt nipple involvement were evaluated. Demographic, preoperative pathology and imaging information was collected. Nipple specimens (2 x 2 x 2 cm) were sectioned at 3-mm intervals. Haematoxylin and eosin-stained slides were examined by a breast pathologist for involvement by tumour. Logistic regression analyses of 65 therapeutic procedures identified factors associated with occult involvement and created a predictive model. This was tested on specimens from a further 65 therapeutic procedures. RESULTS: Occult nipple involvement was noted in 32 (24.6 per cent) of 130 mastectomy specimens. In the training set, imaging diameter of the lesion and its distance from the nipple predicted nipple involvement on univariable analysis (P = 0.011 and P = 0.014 respectively). The multivariable logistic regression model was validated in the test set. The areas under the receiver-operating characteristic curve were 0.824 and 0.709 for the training and test sets respectively. CONCLUSION: Three-quarters of women undergoing mastectomy did not have occult nipple involvement. A clinical tool including tumour size and distance from the nipple has been developed to improve patient selection for nipple-sparing mastectomy..

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PURPOSE: To investigate the histologic correlations of the innumerable 2-3-mm radiolucencies that project over the breast, as seen on mammograms. MATERIALS AND METHODS: With institutional review board approval and HIPAA compliance, this work involved detailed x-ray imaging of discarded tissue from two mastectomy specimens, together with histologic examination of the skin and subcutaneous fat and evaluation of the skin during reduction mammoplasty surgery in two patients. RESULTS: Comparison of the histologic findings with the findings on x-ray images demonstrated that the lucencies seen by using mammography are cutaneous caves in the underside of the dermis into which insert columns of fat projecting up from the subcutaneous adipose tissue. This finding was confirmed with evaluation of the skin during reduction surgery. CONCLUSION: As far as is known, this is the first description of a complex of anatomic structures that explain radiolucencies evident by using mammography..

Moderate size series have reported successful nipple-sparing mastectomy using a variety of surgical techniques. This study aimed to understand which aspects of these techniques are safe, necessary, and successful. Eight skin-sacrificing mastectomy specimens were used as ex vivo models of nipple-sparing mastectomy. After inking the resection margins of the specimen, the skin ellipse was elevated in the subcutaneous plane using a scalpel. The retroareolar breast tissue was taken as a margin specimen. The nipple was inverted and the nipple core removed. The hollowed-out nipple remnant (which would have remained with the patient in a true nipple-sparing mastectomy) was submitted for confirmatory histopathologic analysis. Precise identification of the duct margin directly beneath the nipple proved difficult once the duct bundle had been divided. Successful retroareolar margin identification was achieved by grasping the duct bundle with atraumatic forceps as soon as it became exposed. A cut made below and above the forceps resulted in a full cross-section of the duct bundle. Nipple core tissue was difficult to excise in one piece and cannot be oriented, thus complete evaluation of the specimen required examination of multiple levels. Histologic artifacts caused by freezing may be present in frozen sections of nipple core and retroareolar margin specimens; the impact of such changes must be considered when developing institutional protocols for this procedure. Evaluation of the hollowed-out nipple revealed that the inverted nipple must be substantially thinned to remove all ducts. Modification of technique resulted in more complete excision of duct tissue. This series of ex vivo procedures provides information that can be used to modify surgical and pathologic techniques for nipple-sparing mastectomy. When performing nipple-sparing mastectomy for breast cancer, these measures may be advisable as complements to careful patient selection..

BACKGROUND: The anatomy of the nipple has become clinically relevant. Diagnostic techniques access the breast through nipple ducts and surgeons offer nipple-sparing mastectomy. There is variation in the number of ducts reported and little is known about the spatial location of ducts, their size, and their relationship to orifices on the surface. METHODS: Nipple specimens were taken from 129 consecutive mastectomies. Each was sectioned coronally into 3 mm blocks and one section was prepared from each block. The number of ducts and cross-sectional areas of nipple and duct 'bundle' were recorded. Three nipples were sectioned at 50 mum intervals and digitally reconstructed in three dimensions. RESULTS: The median number of ducts was 23 (interquartile range 19-28). Reconstructions and summary data from 25 nipples show a central duct bundle narrowing to form a 'waist' as the ducts enter breast parenchyma. A three-dimensional reconstruction focusing on one nipple tip demonstrated 29 ducts arising from 15 orifices. Beneath the skin, most ducts are very narrow, gradually becoming larger deeper within the nipple. CONCLUSIONS: This work demonstrates that many ducts share a few common openings onto the surface of the nipple, explaining the observed discrepancy between number of ducts and of orifices. Neither duct diameter nor position predicts whether a duct system will terminate close to the nipple or pass deeper into the breast. These new insights into nipple anatomy will be of use in considering the reliability of a ductal approach to diagnosis and in planning nipple-sparing mastectomy..

Male breast cancer in general is treated by modified radical mastectomy. Data have emerged supporting the replacement of the axillary lymph node dissection by a sentinel lymph node biopsy in the male patient with breast carcinoma. Local therapy in the breast continues to be primarily mastectomy. The reasons suggested for this include the central location of many of the male breast tumors and the paucity of breast tissue. Our experience with breast conservation over the last decade in male breast carcinoma and a review of the literature is outlined here. Between 1996 and 2006, seven men underwent breast conservation for breast carcinoma and to date with a median follow-up of 67 months, there have been no local recurrences. Breast carcinoma in males can be treated with breast conservation with acceptable local recurrence. Breast-conserving surgery in male breast cancer patients should be considered an option in patients without overt nipple/areolar involvement..

PURPOSE: We present our experience with sentinel lymph node (SLN) biopsy in men with breast cancer and review the literature published to date. Consecutive men with breast cancer undergoing SLN biopsy were identified in our prospectively maintained database. A PubMed search for "male breast cancer" and "sentinel node biopsy" was performed. PATIENTS AND METHODS: Thirty patients underwent 31 SLN biopsy procedures between 1996 and 2006. Twenty-five patients presented with a palpable mass, and 13 underwent surgical biopsy for diagnosis. The sentinel lymph node was successfully identified in 90%; 61% of SLN biopsies were positive and, in 65% of this group, the sentinel node was the only positive node. RESULTS: Combined data from the literature from 110 procedures resulted in an identification rate of 96%, positive sentinel nodes in 45% and the sentinel node as the only positive node in 56%. Only 13 patients underwent completion axillary node dissection after a negative SLN biopsy; none were false negatives. This series extends previous knowledge about SLN biopsy in men with respect to diagnostic biopsy, type of mapping agent, lymphoscintigraphy, and location of injection site. The identification rate mirrors that of large randomized trials of women with breast cancer. CONCLUSION: The high rate of lymph node-positive disease, even in this series of patients with clinically node-negative disease, reflects the later presentation of breast cancer in men..

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Transformation of differentiated thyroid cancer into poorly differentiated carcinoma is rare. This report describes a case in which preoperative fine needle aspiration suggested a squamous cell carcinoma whereas needle core biopsy favoured an undifferentiated carcinoma of probable thyroid origin. Histology of the subsequent total thyroidectomy specimen revealed a biphasic tumour comprising areas of tall cell papillary carcinoma merging with moderately to poorly differentiated squamous cell carcinoma. The immunohistochemical findings are discussed in detail..

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We report that injecting an E1-deleted, non-replicating, human adenovirus type 5 vector into the brain leads to an inflammatory response. Much of this inflammation is induced directly by the virion particles themselves rather than through the expression of new proteins from the vector. The severity of inflammation was found to depend on the strain of inbred rat used: PVG rats have less inflammation than AO rats in response to a vector injection. Twelve hours after injection of adenovirus vectors into the striatum of AO rats, leukocytes were seen marginating to the walls of nearby blood vessels. By two days there was a large increase in major histocompatibility complex class I expression and a heavy infiltration of leukocytes, mainly macrophages and T cells. Retrograde transport of adenovirus to neurons of the substantia nigra was associated with a delayed and less intense inflammation at this distant site. Although AO and PVG rats showed comparable responses in the striatum up to six days, at later times PVG rats had less intense inflammation. In spite of the inflammatory response, vector-driven expression of the marker protein beta-galactosidase and an adenovirus early protein was seen for at least two months following the injection, although expression declined with time. The observation that adenovirus gene transfer leads to an inflammatory response in the brain must be taken into account when planning and interpreting experiments with these vectors. Furthermore, we conclude that using an appropriate strain of rat can diminish some aspects of the inflammation..