BACKGROUND:The purpose of this study was to evaluate the prognostic value of the multigene EndoPredict test in prospectively collected data of patients screened for the randomized, double-blind, phase III UNIRAD trial, which evaluated the addition of everolimus to adjuvant endocrine therapy in high-risk, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer. PATIENTS AND METHODS:Patients were classified into low or high risk according to the EPclin score, consisting of a 12-gene molecular score combined with tumor size and nodal status. Association of the EPclin score with disease-free survival (DFS) and distant metastasis-free survival (DMFS) was evaluated using Kaplan-Meier estimates. The independent prognostic added value of EPclin score was tested in a multivariate Cox model after adjusting on tumor characteristics. RESULTS:EndoPredict test results were available for 768 patients: 663 patients classified as EPclin high risk (EPCH) and 105 patients as EPclin low risk (EPCL). Median follow-up was 70 months (range 1-172 months). For the 429 EPCH randomized patients, there was no significant difference in DFS between treatment arms. The 60-month relapse rate for patients in the EPCL and EPCH groups was 0% and 7%, respectively. Hazard ratio (HR) supposing continuous EPclin score was 1.87 [95% confidence interval (CI) 1.4-2.5, P < 0.0001]. This prognostic effect remained significant when assessed in a Cox model adjusting on tumor size, number of positive nodes and tumor grade (HR 1.52, 95% CI 1.09-2.13, P = 0.0141). The 60-month DMFS for patients in the EPCL and EPCH groups was 100% and 94%, respectively (adjusted HR 8.10, 95% CI 1.1-59.1, P < 0.0001). CONCLUSIONS:The results confirm the value of EPclin score as an independent prognostic parameter in node-positive, hormone receptor-positive, HER2-negative early breast cancer patients receiving standard adjuvant treatment. EPclin score can be used to identify patients at higher risk of recurrence who may warrant additional systemic treatments.

Abstract Aim Breast cancer is the most common cancer worldwide, with incidence and mortality rates significantly worse in the developing world. There is a need to improve general health professional’s knowledge of breast disease. The recent COVID-19 pandemic has led to an increase in use of online resources, and remote teaching has had a significant role in medical education particularly post-pandemic. This project aims to assess available breast disease related online resources for use in the context of medical undergraduate education in low and lower-middle income countries. Method A search for online resources was conducted using generic search engine and specialist databases. In the planning phase, predefined search terms were selected, and exclusion and inclusion criteria were identified. In the search execution phase resources were searched for, and the main target and resources type were recorded. In the screening and information management phase resources identified were assessed for comprehensiveness using the Royal College of Surgeons Breast learning outcomes. Results A total of 33 e-resources were identified that met predefined criteria. This included text-based websites (n = 19), tutorials (n = 8), and video resources (n = 6). The majority of resources were aimed at patients (n = 12). None of the resources identified met all 11 outcomes outlined by the Royal College of Surgeons, however most resources met 10 of the learning objectives (n = 7). Conclusions There was a good selection of available educational resources in the area of breast disease, however further exploration of the suitability and usefulness of e-resources in the setting of low and lower-middle income countries is required.

Enzalutamide (enz), has demonstrated substantial preclinical anti-tumour activity in both triple-negative breast cancer (TNBC) and oestrogen receptor positive (ER+ve) breast cancer (BC). ARB was a short-term preoperative window of opportunity (WOO) study that aimed to assess the anti-tumour effects of enz in ER+ve BC and TNBC. An ER+ve BC cohort included 194 women, randomised 2:1 to enzalutamide + exemestane (enz+exe) (130 pts) or exemestane (exe) alone (64 pts). Patients (pts) were stratified by histological grade, level of ER expression and geographic region. An androgen receptor positive (AR+ve), TNBC cohort included 27 women treated with enz alone. All pts were newly diagnosed, with a tumour size ≥1cm and ECOG PS 0-2. The primary endpoint for the ER+ve cohort was inhibition of tumour-cell proliferation, measured by change in Ki67 expression, determined centrally. For the AR+ve cohort, the primary endpoint was individual anti-proliferative response (≥50% fall in Ki67 expression). Analyses presented are for the per-protocol population. Secondary endpoints included induction of apoptosis (Caspase3) and safety. Biomarker exploratory endpoints analysis is ongoing. Baseline (BL) characteristics were similar between both study arms. The incidence of related AE’s were consistent and as expected for the study drugs. In the ER+ve cohort, geometric mean post-treatment percentage (%) reduction of Ki67 was 56% (95% CI, 47%-63%) for exe alone and 60% (95% CI, 53%-66%) for enz+exe. Ki67-response was 54% for exe alone and 63% for enz+exe (one-sided p-value=0.19). Planned sub analyses showed a significant interaction of response to enz+exe with molecular subtype. Pts with Luminal A (LumA) tumours had a higher Ki67 response with enz+exe compared to exe alone (64% vs 38%, one-sided p-value=0.03). Ki67 response was similar for both treatments for LumB tumours (enz+exe, 63%; exe alone, 71%, one-sided p-value=0.36). In the TNBC AR+ve cohort treated with enz alone, geometric mean post-treatment % reduction of Ki67 was 8% (95% CI, -8%-21%). Ki67-response was 5%. No difference was seen overall in inhibition of Ki67 expression after treatment with enz. However, subgroup analysis did show a possible response in LumA pts.

AIM:To assess whether ultrasound features of breast cancer are associated with breast cancer specific survival (BCSS). MATERIALS AND METHODS:Within a single breast service, data was collected prospectively (April 2010-April 2012) from 319 consecutive women (mean age 63 years) with 335 ultrasound-visible invasive breast cancers. Ultrasound features were evaluated retrospectively from the recorded images according to the Breast Imaging Reporting and Data System (BI-RADS) lexicon by a radiologist blinded to outcomes. Survival and cause of death were ascertained from local and national sources. Kaplan-Meier survival curves were generated, and statistical significance tested using the log-rank test. RESULTS:Mean follow-up in those alive was 80.9 months. Thirty breast cancer deaths and 45 non-breast cancer deaths occurred. Five-year BCSS in the presence of distal acoustic enhancement was 76% compared to 88%, 96%, and 100% for those with distal shadowing, no distal effect or combined effect respectively (p<0.0002). Patients with sonographic skin involvement had 73% 5-year BCSS compared to 92% for no skin involvement (p<0.0001). Focal oedema was associated with 56% 5-year BCSS compared to 89% for those without (p=0.0002). A significant association was demonstrated between ultrasound tumour size and BCSS (p<0.0001). At multivariate analysis, skin changes, distal enhancement, and focal oedema maintained prognostic significance. CONCLUSION:Distal enhancement, focal oedema, and skin involvement have strong associations with breast cancer death. These factors could be taken into account, along with lesion size and other commonly used preoperative prognostic features, when considering management of women with breast cancer.

AIM:To determine if imaging features of lesions with a core biopsy suggestive of a phyllodes tumour can be used to identify which lesions require surgical excision with margins. MATERIALS AND METHODS:Thirty-one lesions were identified from a prospective database of ultrasound visible masses. Demographic, mammographic, and ultrasound features were assessed while blinded to surgical outcome. Features of those lesions requiring a margin and those that did not were compared. Statistical significance was established using the chi-square test and receiver operating characteristic (ROC) curves. RESULTS:Thirteen lesions (42%) required a margin and 18 lesions (58%) did not. Features found significantly more frequently in those requiring a margin were a poorly defined margin on mammography (7/9 [78%] versus 4/13 [31%]; p=0.04) and at ultrasound, an irregular margin (8/13 [62%] versus 3/18 [17%]; p=0.01), micro-lobulations (7/13 [54%] versus 3/18 [17%]; p=0.028), mixed echogenicity (9/13 [69%] versus 1/18 [6%]; p=0.0002), echogenic clefts (6/13 [46%] versus 1/18 [6%]; p=0.007), posterior enhancement (9/11 [82%] versus 6/18 [33%]; p=0.01), large size (p=0.003) and stiffness at shear-wave elastography (p=0.026). All six screen-detected lesions were benign. CONCLUSIONS:There are multiple preoperative features that can be used to guide surgical management of lesions with a preoperative core biopsy result suggestive of a phyllodes tumour.

Abstract Background: Although preclinical data suggest that combining PI3K inhibitors with endocrine therapy may overcome resistance, results from randomized clinical trials have failed to identify a subgroup of patients that derive a substantial benefit. This preoperative window study assessed whether adding the PI3K inhibitor pictilisib can increase the anti-tumor effects of anastrozole in primary breast cancer and aimed to identify the most appropriate patient population for combination therapy. Methods: In this randomized, open-label, phase 2 study, 167 postmenopausal women with newly diagnosed, operable, ER-positive, HER2-negative breast cancers were recruited. Participants were randomly allocated (2:1, favoring the combination) to two-weeks of preoperative treatment with anastrozole 1 mg once daily or the combination of anastrozole 1mg with pictilisib 260 mg once daily. The primary endpoint was inhibition of tumor cell proliferation, as measured by change in Ki-67 protein expression between tumor samples taken before and at the end of treatment. Secondary endpoints include induction of apoptosis (Caspase3) and safety. Comprehensive biomarkers analyses included targeted NGS of a comprehensive cancer panel of >400 genes (Ampliseq Comprehensive Cancer panel), copy number variation analyses, and pre- and post-treatment reverse-phase protein arrays (RPPA) and RNA profiling (NanoString nCounter platform). Results:There was significantly greater geometric mean Ki67 suppression of 82.5% (90% CI, 78.3%-85.8%) for the combination vs 70.7% (61.0%-78.0%) for anastrozole [geometric mean ratio (combination/ anastrozole) 0.60 (0.58-0.85);p=0.01]. Higher baseline Ki67, Luminal B status and/or negative PR status were associated with increased benefit from adding pictilisib. A significant interaction was observed between PIK3CA mutation subtypes [helical domain mutations (HD), kinase domain mutations (KD), wildtype (WT)] and mean Ki67 suppression; the combination/anastrozole geometric mean ratio of Ki67 suppression was 0.48 (0.27-0.84; p=0.02) for patients with HD mutations and 0.63 (0.39–1.0; p=0.05) for patients with PIK3Ca WT, compared to 1.17 (0.57–2.41; p=0.64) for patients with KD mutations. This was largely due to patients with HD mutations showing a particularly poor response to anastrozole alone [mean Ki67 suppression 53.9% (9.5%-76.5%)], that was reversed by the addition of pictilisib [mean Ki-67 suppression 78.1% (71.0%-83.4%)]. On the other hand, patients with KD mutations responded well to anastrozole alone [mean Ki-67 suppression 77.7% (57.0%-88.4%)] and showed no benefit from the addition of pictilisib [mean Ki-67 suppression 73.9% (59.8%-83.0%)]. There was no significant difference in induction of apoptosis between treatment groups. Comprehensive pre- and post-treatment biomarkers analyses will be presented. Conclusions: Adding pictilisib to anastrozole significantly increases the anti-proliferative response to preoperative treatment with anastrozole. A significant interaction was observed between PIK3CA mutation subtypes, with patients with helical domain mutations showing a particularly poor response to anastrozole alone that was reversed by the addition of pictilisib. Citation Format: Schmid P, Pinder S, Wheatley D, Zummit C, Macaskill EJ, Hu J, Price R, Bundred N, Hadad S, Shia A, Sarker S-J, Lim L, Mousa K, O'Brien C, Wilson TR, Lackner MR, Gendreau S, Gazinska P, Korbie D, Trau M, Mainwaring P, Thompson A, Purushotham A. Interaction of PIK3CA mutation subclasses with response to preoperative treatment with the PI3K inhibitor pictilisib in patients with estrogen receptor-positive breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-02.

AIMS: To assess the feasibility and acceptability of large-gauge percutaneous removal of the axillary sentinel lymph node (SLN) using dual gamma probe and ultrasound guidance. MATERIALS AND METHODS: Technetium nanocolloid was administered the day before surgery. On the day of surgery, potential SLNs were identified with gamma probe and ultrasound scanning. A 7 G vacuum-assisted biopsy (VAB) device was inserted percutaneously deep to the target node and the node(s) removed. The gamma probe was used to confirm removal of radiolabelled tissue. At surgery, any residual radiolabelled or blue nodes were removed. Morbidity was assessed via (1) a pain questionnaire immediately after the percutaneous procedure, (2) relevant items from the FACT B+4 questionnaire 7-10 days after surgery, and (3) case note review 1 month after surgery. RESULTS: Twenty-two patients consented and 20 patients underwent the procedure. Radiolabelled nodal tissue was obtained in 18/20 (90%). The mean procedure time was 11 minutes. Four of 18 patients had metastatic disease identified in the VAB excision tissue with 100% sensitivity for axillary metastasis. At axillary surgery, additional intact SLN or fragments were found in 14 patients. No additional metastatic disease was found at surgery. One patient suffered a pneumothorax during instillation of local anaesthetic. The median pain score was 10/100 by visual analogue scale. Immediate post-procedure haematoma was common (14 of 20) and prolonged manual compression frequent. CONCLUSION: VAB removal of sentinel nodes using dual scanning is feasible. Although preliminary sensitivity and specificity levels are encouraging, complications may discourage widespread implementation. (C) 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Abstract This abstract was not presented at the symposium.

AIM: The aim of this study is to establish predictors of invasion in lesions yielding an ultrasound-guided biopsy diagnosis of ductal carcinoma in situ (DCIS).MATERIALS AND METHODS: Patients subjected to ultrasound-guided core biopsy yielding DCIS were studied. At shear-wave elastography (SWE) a threshold of 50 kPa was used for mean elasticity (E-mean) to dichotomise the elasticity data between invasive and non-invasive masses. Data recorded included the mammographic and ultrasound features, the referral source, and grade of DCIS in the biopsy. The chi-square test was used to detect statistical significance.RESULTS: Of 57 lesions, 24 (42%) had invasion at excision. Symptomatic patients and patients with stiff lesions were more likely to have invasion than patients presenting through screening and with soft lesions (58% [14 of 24] versus 30% [10 of 33], p=0.03) and (51% [20 of 39] versus 22% [4 of 18], p=0.04). No other factors showed a relationship with invasion. Combining the two predictors of invasion improved risk stratification with symptomatic and stiff lesions having a risk of invasion of 67% (12 of 18) and soft lesions presenting at screening having only a 17% (2 of 12) risk of invasion (p=0.02).CONCLUSION: Stiffness on SWE and the referral source of the patient are predictors of occult invasion in women with an ultrasound-guided core biopsy diagnosis of DCIS. (C) 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Systematic review of the complications following isolated calf deep vein thrombosisRevisión sistemática de las complicaciones

PURPOSE:Debate continues on what is an adequate margin width to define a clear margin and whether there is a need to excise pectoral fascia or remove skin in breast conserving surgery. This study set out to provide answers to these questions. PATIENTS AND METHODS:1411 patients with invasive breast cancer were treated by breast conserving surgery and post-operative whole breast radiotherapy from January 2000 to December 2005. Distance from each margin to any in situ or invasive cancer was measured and recorded. If full thickness of breast tissue was removed no re excision of anterior and posterior margins was performed even if disease was <1 mm from a margin. Patients ≤50 years of age and those with anterior or posterior margins <1 mm to invasive cancer had a radiation boost. Median follow-up time was 6.4 years. RESULTS:Local in breast tumour relapse (IBTR) occurred in 50 patients. The overall actuarial IBTR rate at 5 years was 2.2%. There was no difference in IBTR when comparing patients with radial margins of 1-5 mm or 5-10 mm. Anterior and posterior margins <1 mm or with ink on tumour cells were not associated with an increase in IBTR. CONCLUSION:There is no justification for radial margins of greater than 1 mm. If the anterior or posterior margin is <1 mm and full thickness of breast tissue has been removed, then re excision of these margins is unnecessary if boost radiotherapy is delivered.

BACKGROUND:Completeness of excision is the most important factor influencing local recurrence after breast-conserving surgery (BCS). The aim of this case-control study was to determine factors influencing incomplete excision in patients undergoing BCS.METHODS:Women with invasive breast cancer treated by BCS between 1 June 2008 and 31 December 2009 were identified from a prospectively collected database in the Edinburgh Breast Unit. The maximum size of the tumour, measured microscopically, was compared with the size estimated before operation by mammography and ultrasound imaging. A multivariable analysis was performed to investigate factors associated with incomplete excision.RESULTS:The cohort comprised 311 women, of whom 193 (62·1 per cent) had a complete (CE group) and 118 (40·7 per cent) an incomplete (IE group) excision. Mammography underestimated tumour size in 75·0 per cent of the IE group compared with 40·7 per cent of the CE group (P < 0·001). Ultrasound imaging underestimated tumour size in 82·5 per cent of the IE group compared with 56·5 per cent of the CE group (P < 0·001). The risk of an incomplete excision was greater when mammography or ultrasonography underestimated pathological size: odds ratio (OR) 4·38 (95 per cent c.i. 2·59 to 7·41; P < 0·001) for mammography, and OR 3·64 (2·03 to 6·54; P < 0·001) for ultrasound imaging. For every 1-mm underestimation of size by mammography and ultrasonography, the relative odds of incomplete excision rose by 10 and 14 per cent respectively.CONCLUSION:Underestimation of tumour size by current imaging techniques is a major factor associated with incomplete excision in women undergoing BCS.

Introduction: This multicentre randomised controlled trial investigated whether a computed tomography (CT) scan of the axilla could more accurately assess whether the axillary lymph nodes were involved with malignancy in patients with newly diagnosed breast cancer and therefore influence surgical decision-making with regard to axillary surgery.Methods: Patients with newly diagnosed breast cancer (via screening and symptomatic routes) at two NHS Trusts in the North East of England were recruited and randomised in equal numbers.Both groups received routine diagnostic and surgical care (usual care).In addition, one group received a CT scan of their axilla on the same side as the breast cancer.Results: The study recruited 297 patients, of whom 291 contributed to findings.CT scan-guided care did not result in a change in the need for a second operation, with about 20% of both groups needing further surgery.Patients within the two groups were similar before treatment, had similar types and grade of cancer, experienced similar pattern complications and reported similar experiences of care.Conclusion: New diagnostic imaging technologies regularly enter NHS centres of excellence as research tools.It is important these are evaluated rigorously before becoming routine care.In patients newly diagnosed with breast cancer, CT-augmented diagnosis of cancer in the axilla was not found to improve surgical outcomes or patient experience.

Background: Sentinel node biopsy as a surgical method of axillary staging for early breast cancer has been widely accepted as an alternative to traditional four-node axillary node sampling, and is the recommended technique by the Association of Breast Surgery in the United Kingdom. In selected units axillary sampling has been compared with either radioisotope sentinel node or blue dye only techniques with comparable node positivity rates. There are no studies directly comparing combined method sentinel node biopsy (SNB) with conventional axillary (four) node sampling (ANS).Methods: Data for all patients undergoing axillary staging by axillary node sample or sentinel node biopsy were collected, including those proceeding to axillary clearance as a second procedure, but excluding those undergoing axillary clearance as a first procedure.Results: From January 2005 to January 2011, 641 axillary staging procedures were performed (SNB n = 231 (36.0%), ANS n = 410 (64.0%)). Baseline tumour characteristics were similar for the two groups except for a higher frequency of breast conservation in the SNB group (95.6 vs. 75.6%; p < 0.0001). The proportion of cases with positive nodes was higher in the SNB group (20.8 vs. 14.4%; p = 0.042). In patients who had presented with symptomatic disease, there was a significantly higher node positivity rate with SNB (30.9%) than with ANS (15.5%; p = 0.002), despite similar baseline characteristics in both groups.Conclusion: Combined method sentinel node biopsy is more sensitive at detecting low volume axillary disease than traditional four-node sample. (C) 2012 Elsevier Ltd. All rights reserved.

AIM: To determine the diagnostic yield of each of three core passes when sampling abnormal lymph nodes in patients presenting with breast cancer.MATERIALS AND METHODS: All patients suspected of having breast cancer had axillary ultrasound as part of initial assessment. Radiologically abnormal nodes (cortical thickness >2.3 mm or round shape) were biopsied with three passes of a 22 mm throw 14 G core biopsy needle and sent for histopathology in separate numbered pots. Data were collected prospectively, and analysis performed on the data of 55 consecutive patients who had positive nodes on at least one core biopsy needle pass.RESULTS: Of 55 patients with a positive node on core biopsy, tumour was noted in all three cores taken in 39 (70.9%). Lymph node metastasis was detected in 45 (81.8%) first core biopsies. With the first two cores taken, positive results were detected in 53 of 55 cases (96.4%). In both cases where tumour was only found on a third core biopsy pass, no lymph node tissue was present in the first two biopsy passes.CONCLUSION: Two well-directed 14 G core biopsy samples from an abnormal axillary node are adequate for diagnosis of breast cancer metastasis. (C) 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Background: Complete tumour excision in breast conserving surgery (BCS) is critical for successful treatment; involved circumferential resection margins are associated with increased disease recurrence. However, the importance of an involved anterior margin is less clear. The purpose of this study was to audit an aggressive approach to involved anterior margins and hence assess whether anterior margin re-excision yields clinical benefit. Material and Methods: A retrospective case note and pathology review was performed for all patients who underwent BCS between 2006 and 2010 through a single cancer centre. An involved margin was defined as Conclusions: Re-excision of involved anterior margins rarely excises residual disease and may be unnecessary. Multidisciplinary teams should consider whether further therapy for an involved anterior margin is required on a patient by patient basis. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-12-04.