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Background: Breast cancer remains the most common cancer in women and a leading cause of death. Elderly people have a higher incidence of breast cancer since it increases with age. Furthermore, the extended life expectancy and advances in imaging techniques have led to an increased number of cases. Guidelines concerning the management of this specific age group are rare, mainly due to underrepresentation of seniors in clinical trials. Moreover, increased frailty, comorbidities, and a poor performance status make it complex to determine the best therapeutic approach. Summary: In this review, we attempt to summarize the current literature and aim to provide specific approaches and recommendations for prompt diagnosis, treatment, and management of breast cancer in the elderly. Key Messages: The establishment of applicable protocols is imperative and efforts are being made in this direction. A careful geriatric assessment and adequate consultation should be the standard of care and patient's preferences should always be considered. © 2021 S. Karger AG, Basel. Copyright: All rights reserved.

During the 1990s a new innovative kind of drama started to show up in Great Britain, known as in-yer-face theatre, originating from young writers who challenged conventional theatrical codes and presented provocative and aggressive material on stage in order to shock audiences and raise public consciousness (Sierz 2001). They were innovative in terms of content and form and established a new theatre language which was more direct, raw and offensive. This study examines a representative play of this genre, Attempts on her Life by Martin Crimp (1997) and two Greek translations of it (1999, 2007). The aim is to investigate how impoliteness and the shock effects are rendered and if the primary aim of in-yer-face theatre is achieved in these two Greek texts. Τhe study elicits data through a questionnaire addressing (a) translation postgraduates and (b) professionals related to the theatre industry. Results show that both groups perceive impoliteness in both stage translations in a similar way: the latest translation (2007) seems to fulfill the goals of in-yer-face theatre, a bit more eloquently. The significance of this study lies in highlighting the educational value of stage translation data: they can shed light on pragmatic phenomena (like impoliteness) cross-culturally which fit the needs of theatre genres for the benefit not only of researchers but also of theatre practitioners. © 2022, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

BACKGROUND/AIM: Soy contains genistein and daidzein isoflavones. Isoflavones are phytoestrogens, with a similarity in structure to human 17-β estradiol hormone. They imitate the action of estrogen on organs by binding and activating estrogen receptors. Numerous studies have examined the relationship between soy consumption and breast cancer but not the amount of consumption itself. We performed a systematic review of the literature in order to determine whether the amount of soy and isoflavones consumed has a positive effect in pre- and post-menopausal women. MATERIALS AND METHODS: Data gathering was performed following PRISMA guidelines. Narrowing down the result set for all relevant data was performed via title, abstract, full-text evaluation and the snowball procedure. The selected articles had all relevant data extracted. Analysis of the data was performed using Cochrane's Review Manager statistical analysis tool in order to draw conclusions regarding the positive effect for the amount of soy and isoflavones consumed. RESULTS: Significant results were found when statistically analyzing data from prospective studies which compared soy isoflavones consumption, breast cancer risk and occurrence. The data were indicative of a clear inverse correlation between the amount of isoflavones consumed and breast cancer occurrence in pre- and post-menopausal women. CONCLUSION: The consumption of soy isoflavones can reduce the risk of breast cancer in pre-menopausal and post-menopausal women. Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Despoina Kalapanida,1 Flora Zagouri,1 Maria Gazouli,2 Andriani Tsiakou,3 Eleni Zografos,2 Constantine Dimitrakakis,4 Spyridon Marinopoulos,4 Aris Giannos,4 Theodoros N Sergentanis,1 Efstathios Kastritis,1 Evangelos Terpos,1 Meletios-Athanassios Dimopoulos11Department of Clinical Therapeutic, Alexandra Hospital, Medical School, University of Athens, Athens, Greece; 2Department of Basic Medical Sciences, Laboratory of Biology, University of Athens School of Medicine and Laboratory of Cell and Gene Therapy, Biomedical Research Foundation of the Academy of Athens, Athens, Greece; 3First Department of Dermatology, Syggros Hospital, University of Athens School of Medicine, Athens, Greece; 4Department of Obstetrics and Gynaecology, Alexandra Hospital, Medical School, University of Athens, Athens, GreeceAim: The purpose of this study is to evaluate the role of MET T1010I and MET rs40239 as potential risk factor and/or prognostic markers in patients with triple-negative breast cancer (TNBC).Methods: 114 samples of DNA from paraffin-embedded breast normal tissues of patients with TNBC and 124 samples of healthy controls were collected and analyzed for MET T1010I and MET rs40239 polymorphisms.Results: MET T1010I CT genotype was associated with increased risk of TNBC in both univariate and multivariate analysis. The status of rs40239 was not associated with a higher risk for TNBC at either the univariate or the multivariate analysis. None of the examined polymorphisms was associated with overall survival at the univariate or multivariate Cox regression analysis (adjusted HR=1.35, 95% CI: 0.31–5.97 for MET T1010I CT/TT vs CC; adjusted HR=1.78, 95% CI: 0.73–4.35 for rs40239 AG/GG vs AA).Conclusion: Our case–control study suggests that MET T1010I seems to be a risk factor for TNBC in the Caucasian Greek population, in contrast with MET rs40239, where no correlation was found.Keywords: SNPS, MET T1010I, MET rs40239, triple-negative breast cancer, biomarker

Background: Pregnancy-associated breast cancer (PABC) defined as breast cancer diagnosed during gestation, lactation or within 1 year after delivery, represents a truly challenging situation with significantly increasing incidence rate. The genomic background of PABC has only recently been addressed while the underlying mechanisms of the disease still remain unknown. This analysis aims to further elucidate the frequency of PABC cases attributable to genetic predisposition and identify specific cancer susceptibility genes characterizing PABC. Methods: A comprehensive 94-cancer gene panel was implemented in a cohort of 20 PABC patients treated in our clinic and descriptive correlation was performed among the results and the patients’ clinicopathological data. Results: In the present study, 35% of PABC patients tested carried pathogenic mutations in two known cancer predisposition genes (BRCA1 and CHEK2). In total, 30% of the patients carried BRCA1 pathogenic variants. An additional 5% carried pathogenic variants in the CHEK2 gene. Variants of unknown/uncertain significance (VUS) in breast cancer susceptibility genes BRCA2, CHEK2 and BRIP1 were also identified in three different PABC patients (15%). Not all patients carrying germline mutations reported known family history of cancer. Conclusions: Genetic testing should be considered as an option for PABC patients since the disease is highly associated with genetic susceptibility among other predisposing factors. Germline mutation identification may further modify PABC management approach and improve the prognostic outcome. © 2021, The Author(s).

Aim: The purpose of this study is to evaluate the role of MET T1010I and MET rs40239 as potential risk factor and/or prognostic markers in patients with triple-negative breast cancer (TNBC). Methods: 114 samples of DNA from paraffin-embedded breast normal tissues of patients with TNBC and 124 samples of healthy controls were collected and analyzed for MET T1010I and MET rs40239 polymorphisms. Results: MET T1010I CT genotype was associated with increased risk of TNBC in both univariate and multivariate analysis. The status of rs40239 was not associated with a higher risk for TNBC at either the univariate or the multivariate analysis. None of the examined polymorphisms was associated with overall survival at the univariate or multivariate Cox regression analysis (adjusted HR=1.35, 95% CI: 0.31–5.97 for MET T1010I CT/TT vs CC; adjusted HR=1.78, 95% CI: 0.73–4.35 for rs40239 AG/GG vs AA). Conclusion: Our case–control study suggests that MET T1010I seems to be a risk factor for TNBC in the Caucasian Greek population, in contrast with MET rs40239, where no correlation was found. © 2019 Kalapanida et al.

Background: The emphasis on aesthetic outcomes and quality of life after breast cancer surgery has motivated breast surgeons to develop oncoplastic breast conserving surgery (OPS). Training programs are still rare in most countries, and there is little standardization, which challenges the scientific evaluation of these techniques. This systematic review aims to assess oncological and cosmetic outcomes of OPS. Methods: After a strict selection process with precise inclusion and exclusion criteria, oncologic and aesthetic outcomes of oncoplastic surgery were searched, using the MEDLINE database up to September 30th, 2017. Available published literature was classified in levels of evidence. After a thorough screening process, only studies with the best level of evidence were included on selection. Systematic reviews and meta-analyses were not included for methodological reasons. Results: Titles and abstracts of 2.854 citations were identified and after screening 15 prospective studies including 1.391 patients were reviewed and scored in detail. Local relapse was found in 2.8% of cases with a wide range of follow-up (from 6 to 74 months). Close margins were retrieved in 11% of cases and positive margins in 9.4% of cases. Mastectomy was implemented in 6.9% of breast cancer patients to whom OPS was performed. Good cosmetic outcomes were detected in 90.2% of patients undergoing OPS, leaving open issues for who should perform cosmetic evaluation and which method should be used. Conclusion: Tumor margins, mastectomy rates, and cosmetic outcomes of OPS have to be further improved by standardizing various aspects of OPS. Research efforts should focus on level I evidence assessing both oncological and aesthetic outcomes of OPS and survival rates. © 2019, The Japanese Breast Cancer Society.

Introduction: Management and optimal follow-up of early breast cancer survivors remain up to this day a challenge due to the lack of well-established guidelines. Multiple medical societies, organizations and working groups have provided recommendations for follow-up but there is no uniform, globally approved algorithm to guide clinical practice. Methods: A systematic review was performed to identify and evaluate discrepancies between available guidelines for the follow-up of breast cancer survivors. Results: Differences in the follow-up schedule, laboratory and imaging investigations were noted. In the clinical practice setting, the situation is complicated further by clinicians who often request unnecessary tests not currently incorporated in any of the existing guidelines. Conclusions: Follow-up of patients with early breast cancer needs to become standardized and prospective clinical trials focusing on optimal follow-up are more than mandatory. © 2019, The Japanese Breast Cancer Society.

Aim: The purpose of this study is to evaluate the role of pre-miR34a rs72631823 as potential risk factor and/or prognostic marker in patients with triple negative breast cancer. Methods: 114 samples of DNA from paraffin embedded breast normal tissues of patients with triple negative breast cancer and 124 samples of healthy controls were collected and analyzed for pre-miR34a rs72631823 polymorphism. Results: Pre-miR34a rs72631823 A allele was associated with increased TNBC risk both in univariate and multivariate analysis. The number of pre-miR34a rs72631823 AA subjects was very small and the association did not reach significance (p = 0.176, Fisher's exact test). The examined polymorphism was not associated with overall survival at the univariate or multivariate Cox regression analysis (adjusted HR = 1.60, 95%CI: 0.64-3.96 for miR34 rs72631823 GA/AA vs. GG). Conclusion: Our case-control study suggests that pre-miR34a rs72631823 A allele is associated with increased triple negative breast cancer risk. © 2018 Kalapanida et al.

Aris Giannos,1 Martin Filipits,2 Flora Zagouri,2,3 Anita Brandstetter,2 Alexandra Tsigginou,1 Maria Sotiropoulou,4 Irene Papaspyrou,4 Theodoros N Sergentanis,5 Theodora Psaltopoulou,5 Alexandros Rodolakis,1 Aris Antsaklis,1 Meletios-Athanasios Dimopoulos,2 Constantine Dimitrakakis1 1Department of Obstetrics and Gynaecology, Alexandra General Hospital, Medical School, University of Athens, Athens, Greece; 2Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; 3Department of Clinical Therapeutics, Alexandra General Hospital, Medical School, University of Athens, Athens, Greece; 4Department ofPathology, Alexandra General Hospital, Athens, Greece; 5Department of Hygiene, Epidemiology and Medical Statistics, Medical School, University of Athens, Athens, Greece Background/aim: In light of the controversial published literature, this study aims to examine the potential prognostic role of AR immunohistochemical expression in triple negative breast cancer (TNBC).Patients and methods: Ninety patients with TNBC were included in this study; the associations between AR expression (Allred score), clinicopathological variables (stage, grade, histological subtype, tumor size, nodal status, age at diagnosis, Ki67 expression, and p53 expression), and overall survival were evaluated.Results: AR expression was not associated with stage, grade, histological subtype, tumor size, nodal status, age at diagnosis, Ki67 expression, and p53 expression. AR immunopositivity was not associated with overall survival either at the univariate or at the multivariate Cox regression analysis (multivariate hazard ratio =0.66, 95% confidence interval: 0.26–1.70, P=0.393).Conclusion: AR expression does not seem to play a prognostic role in TNBC. Keywords: biomarkers, prognosis, AR, triple negative breast cancer

A recurrent large genomic rearrangement (LGR) encompassing exons 23 and 24 of the BRCA1 gene has been identified in breast-ovarian cancer families of Greek origin. Its breakpoints have been determined as c.5406 + 664_*8273del11052 (RefSeq: NM_007294.3) and a diagnostic polymerase chain reaction (PCR) has been set up for rapid screening. In a series of 2,092 high-risk families completely screened for BRCA1 and BRCA2 germline mutations, we have found the deletion in 35 families (1.68%), representing 7.83% of the mutations identified in both genes and 10.3% of the total BRCA1 mutations. In order to characterize this deletion as a founder mutation, haplotype analysis was conducted in 60 carriers from 35 families, using three BRCA1 intragenic microsatellite markers and four markers surrounding the BRCA1 locus. Our results demonstrate a common shared core disease-associated haplotype of 2.89Mb. Our calculations estimate that the deletion has originated from a common ancestor 1450 years ago, which most probably inhabited the Asia Minor area. The particular (LGR) is the third mutation of such type that is proven to have a Greek founder effect in the Greek population, illustrating the necessity for LGRs testing in individuals of Greek descent. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Introduction Giant juvenile fibroadenomas represent only the 0.5% of all fibroadenomas, constituting a rare condition in adolescence. In prepuberty, the presence of this condition is extremely rare. Presentation of case We describe a rare case of a 12- year-old Caucasian girl who presented to our Hospital complaining of a palpable mass with rapid enlargement in her right breast that she had first noticed 3 months ago. Her menarche hadn't occurred yet. Discussion Physical examination showed a giant mass of 15 × 13 cm in the right breast. The patient was further evaluated via ultrasonography showing a sole large lesion of 13 × 12 cm in the right breast. A surgical procedure under general anesthesia was performed. Histopathological findings after the surgical excision were suggestive of giant juvenile fibroadenoma. The patient has a normal breast development over a period of 9 month follow up. Conclusion Giant juvenile fibroadenomas should be included in differential diagnosis of a breast mass in prepubertal girls despite the fact that they are very rare in prepuberty, tend to appear later during adolescence and their prevalence is lower in Caucasians. The remarkable size and the rapid growth of the lesion should not be ruled out in the diagnostic process of an adolescent breast. © 2017

This paper presents results on formal verification of high-speed cryptographic software. We consider speed-record-setting hand-optimized assembly software for Curve25519 elliptic-curve key exchange presented by Bernstein et al. at CHES 2011. Two versions for different microarchitectures are available. We successfully verify the core part of the computation, and reproduce detection of a bug in a previously published edition. An SMT solver supporting array and bit-vector theories is used to establish almost all properties. Remaining properties are verified in a proof assistant with simple rewrite tactics. We also exploit the compositionality of Hoare logic to address the scalability issue. Essential differences between both versions of the software are discussed from a formal-verification perspective.

Pregnancy-associated cancer constitutes an uncommon and difficult to manage clinical situation. It is defined as the cancer diagnosed from the first day of childbearing to 1 year post partum. Coexistence of cancer with pregnancy adds complexity to treatment recommendations, as both the mother and the fetus may be affected. The optimal therapeutic management of pregnant women with cancer diagnosis should take into account, apart from medical factors, a host of other parameters (ethical, psychological, religious, legal, etc). Unfortunately, this situation becomes more complex as more women delay childbearing, and consequently the incidence of cancer during pregnancy is constantly increasing. This manuscript summarises the general principles in managing pregnant patients with cancer and gives detailed instructions in the management of pregnant patients with breast cancer, ovarian cancer, melanoma, lymphoma, lung cancer, soft-tissue sarcoma and cervical cancer. Of note, management of pregnant women with cancer diagnosis should be performed in specialised centres with experience and all cases should be discussed in multidisciplinary meetings composed of multiple specialists (medical oncologists, obstetricians, surgeons, radiologists and paediatricians). © Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Dual-energy contrast-enhanced spectral mammography (CESM) represents a relatively new diagnostic tool adjunct to mammography. The aim of this study was to strengthen the breast imaging-reporting and data system (BIRADS) classification score in order to improve early breast cancer diagnosis. For this reason, we propose a sum score, termed malignancy potential score (MPS), incorporating the standard BIRADS score and our proposed CESM score. From September 2014 to September 2015, 216 females (age range, 26-85 years; mean age 54.6 years) underwent CESM evaluation of mammographic findings that were primarily assessed as BIRADS 2-5. 10 of these patients had bilateral findings; a total of 226 lesions were examined. High-energy image evaluation was based on the intensity of contrast enhancement of the lesion compared with background enhancement, categorized as Type-1, 0, 1 or 2 enhancement. Histopathology reports were compared with imaging assessment. 98 of 226 lesions were malignant and 128 of 226 lesions were benign. The area under the curve was 0.843, 0.888 and 0.917 for mammographic BIRADS score, CESM score and MPS, respectively, with p-value , 0.05. The sensitivity, specificity and accuracy rates were 91.83, 80.47 and 85.40%, respectively, when a best MPS cut-off point of 4 was used. The malignancy potential score (MPS) has higher diagnostic performance than digital mammography or CESM alone. MPS empowers the credibility of the digital mammography BIRADS score and our proposed type of enhancement in dual-energy CESM and is a diagnostic tool that increases the accuracy rate in early breast cancer diagnosis.

Objectives This prospective study was designed to investigate the effect of testosterone, delivered by subcutaneous implants, on the female voice. Methods Ten women who had opted for testosterone therapy were recruited for voice analysis. Voices were recorded prior to treatment and at 3 months, 6 months, and 12 months while on testosterone therapy. Acoustic samples were collected with subjects reading a sentence, reading a paragraph, and participating in a conversation. Significant changes in the voice over time were investigated using a repeated-measures analysis of variance with the fundamental frequency (F-0) as a response variable. Demographic variables associated with characteristics of the voice were assessed. Results There were no significant differences in average F-0 related to smoking history, menopausal status, weight, or body mass index. There was no difference in average fundamental speaking frequency (sentence, paragraph, conversation) between the pre-treatment group and any post-treatment group at 3 and 12 months. There was an increase in sentence speech F-0 at 6 months. Two of three patients with lower than expected F-0 at baseline improved on testosterone therapy. Conclusion Therapeutic levels of testosterone, delivered by subcutaneous implant, had no adverse affect on the female voice including lowering or deepening of the voice.

Supervised learning deals with the inference of a distribution over an output or label space $\CY$ conditioned on points in an observation space $\CX$, given a training dataset $D$ of pairs in $\CX \times \CY$. However, in a lot of applications of interest, acquisition of large amounts of observations is easy, while the process of generating labels is time-consuming or costly. One way to deal with this problem is {\em active} learning, where points to be labelled are selected with the aim of creating a model with better performance than that of an model trained on an equal number of randomly sampled points. In this paper, we instead propose to deal with the labelling cost directly: The learning goal is defined as the minimisation of a cost which is a function of the expected model performance and the total cost of the labels used. This allows the development of general strategies and specific algorithms for (a) optimal stopping, where the expected cost dictates whether label acquisition should continue (b) empirical evaluation, where the cost is used as a performance metric for a given combination of inference, stopping and sampling methods. Though the main focus of the paper is optimal stopping, we also aim to provide the background for further developments and discussion in the related field of active learning., Comment: 17 pages, 4 figures. Corrected some errors and changed the flow of the text

Several approximate policy iteration schemes without value functions, which focus on policy representation using classifiers and address policy learning as a supervised learning problem, have been proposed recently. Finding good policies with such methods requires not only an appropriate classifier, but also reliable examples of best actions, covering the state space sufficiently. Up to this time, little work has been done on appropriate covering schemes and on methods for reducing the sample complexity of such methods, especially in continuous state spaces. This paper focuses on the simplest possible covering scheme (a discretized grid over the state space) and performs a sample-complexity comparison between the simplest (and previously commonly used) rollout sampling allocation strategy, which allocates samples equally at each state under consideration, and an almost as simple method, which allocates samples only as needed and requires significantly fewer samples., Comment: 14 pages, presented at EWRL'08

Testosterone (T) is the most abundant biologically active hormone in women. Androgen receptors (AR) are located throughout the body including the breast where T decreases tissue proliferation. However, T can be aromatized to estradiol (E2), which increases proliferation and hence, breast cancer (BCA) risk. Increased aromatase expression and an imbalance in the ratio of stimulatory estrogens to protective androgens impacts breast homeostasis. Recent clinical data supports a role for T in BCA prevention. Women with symptoms of hormone deficiency treated with pharmacological doses of T alone or in combination with anastrozole (A), delivered by subcutaneous implants, had a reduced incidence of BCA. In addition, T combined with A effectively treated symptoms of hormone deficiency in BCA survivors and was not associated with recurrent disease. Most notably, T+A implants placed in breast tissue surrounding malignant tumors significantly reduced BCA tumor size, further supporting T direct antiproliferative, protective and therapeutic effect. (C) 2015 The Authors. Published by Elsevier Ireland Ltd. All rights reserved.

Introduction: Minor breast concerns in childhood and adolescence are common and lead to increased anxiety among young patients and their families, particularly due to high correlation with breast cancer. However, most breast services aim at managing adults and triaging patients with breast cancer, whereas adolescent medicine specialists or pediatricians are usually not appropriately trained to identify and treat breast pathology. Methods: We reviewed hospital records of all patients attending a pediatric and adolescent gynecology or breast clinic of a tertiary referral hospital, with a breast related symptom, between January 2009 and December 2011. We collected information regarding age at presentation, age at menarche, diagnosis, management and outcome. Results: We identified 81 patients of which 11 presented with an abnormal nipple or areolar secretion, 33 had a palpable lump, 20 had mastitis, and 16 had unequal breast development. One patient presented with virginal breast hypertrophy. Three out of 11 of the patients with an abnormal secretion had a cyst identified on ultrasonography. Out of the palpable lumps 12 were fibroadenomas, 3 were phyllodes tumors, and 14 were cystic in nature. The phyllodes tumors and half of the fibroadenomas were removed. The remaining fibroadenomas remain under regular ultrasonographic follow-up. All cases of mastitis were treated conservatively and resolved with broad spectrum antibiotic treatment. Conclusion: In our series, no malignancies were identified. Although 8 patients required surgical treatment, the majority of cases were treated conservatively. © 2015 North American Society for Pediatric and Adolescent Gynecology.

Background/aim: In light of the controversial published literature, this study aims to examine the potential prognostic role of AR immunohistochemical expression in triple negative breast cancer (TNBC). Patients and methods: Ninety patients with TNBC were included in this study; the associations between AR expression (Allred score), clinicopathological variables (stage, grade, histological subtype, tumor size, nodal status, age at diagnosis, Ki67 expression, and p53 expression), and overall survival were evaluated. Results: AR expression was not associated with stage, grade, histological subtype, tumor size, nodal status, age at diagnosis, Ki67 expression, and p53 expression. AR immunopositivity was not associated with overall survival either at the univariate or at the multivariate Cox regression analysis (multivariate hazard ratio =0.66, 95% confidence interval: 0.26–1.70, P=0.393). Conclusion: AR expression does not seem to play a prognostic role in TNBC. © 2015 Giannos et al.

In recent years, the use of elastography in addition to sonography has become a routine clinical tool for the characterization of breast masses. Studies have investigated the improvement of specificity in differentiating benign from malignant breast masses. Therefore, additional use of elastography could help reduce the number of unnecessary biopsies in benign breast lesions especially in category IV lesions of the ultrasound breast imaging reporting data system. Ultrasound elastography is a cheap, readily available, useful, quick, noninvasive method, but it needs specific training as well as acknowledging technical and pathological factors, which may influence it. Both strain and acoustic radiation force impulse (ARFI) methods have been evaluated in breast lesions. Whereas strain elastography results in qualitative imaging of tissue stiffness due to induced compression, ARFI elastography displays quantitative and qualitative information of tissue displacement. A standardized imaging protocol is essential for an adequate and effective examination, also helping reduce the dependence from operators. Furthermore, knowledge of pitfalls that can be encountered when ultrasound elastography is performed may help avoid erroneous image interpretation. In this article, we describe a practical examination protocol for both strain and ARFI elastography and demonstrate the elastographic imaging findings in benign and malignant breast lesions. Short video clips displaying the technique are included as supplementary material. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

An ever growing number of medical organizations, societies, working groups and governmental agencies issue algorithms i.e. guidelines, of decision making flowcharts in diagnosis and treatment in a variety of diseases. In the field of evidence-based diagnosis and treatment of breast cancer, a large number of guidelines are available both from medical associations and national health departments. Among the most appreciated and utilized comprehensive guides is the European Society for Medical Oncology (ESMO) Breast Cancer Guidelines and from the other side of the Atlantic the National Comprehensive Cancer Network (NCCN) Guidelines in Breast Cancer. Although there is much concordance between the guidelines from these two organizations, it is intriguing to locate their discrepancies also. The aim of this report is to present a number of different points between ESMO and NCCN in the whole spectrum of breast cancer management, from prevention and diagnosis to treatment and follow up. This systematic review was performed in accordance with the PRISMA guidelines using a predefined search strategy and summarizes in detail, the differences between ESMO and NCCN guidelines regarding genetic risk evaluation and screening, surgery, chemotherapy, endocrine treatment, targeted biological agents, radiotherapy, pregnancy and fertility and follow-up. © 2015 Elsevier Ltd.

Various avours of a new research field on (socio-)physical or personal analytics have emerged, with the goal of deriving semantically-rich insights from people's low-level physical sensing combined with their (online) social interactions. In this paper, we argue for more comprehensive data sources, including environmental (e.g. weather, infrastructure) and application-specific data, to better capture the interactions between users and their context, in addition to those among users. To illustrate our proposed concept of synergistic user context analytics, we first provide some example use cases. Then, we present our ongoing work towards a synergistic analytics platform: a testbed, based on mobile crowdsensing and the Internet of Things (IoT), a data model for representing the different sources of data and their connections, and a prediction engine for analyzing the data and producing insights.

Background: Dose-dense sequential chemotherapy including anthracyclines and taxanes has been established in the adjuvant setting of high-risk operable breast cancer. However, the preferable taxane and optimal schedule of administration in a dose-dense regimen have not been defined yet.Methods: From July 2005 to November 2008, 1001 patients (990 eligible) were randomized to receive, every 2 weeks, 3 cycles of epirubicin 110 mg/m2 followed by 3 cycles of paclitaxel 200 mg/m2 followed by 3 cycles of intensified CMF (Arm A; 333 patients), or 3 cycles of epirubicin followed by 3 cycles of CMF, as in Arm A, followed 3 weeks later by 9 weekly cycles of docetaxel 35 mg/m2 (Arm B; 331), or 9 weekly cycles of paclitaxel 80 mg/m2 (Arm C; 326). Trastuzumab was administered for one year to HER2-positive patients post-radiation.Results: At a median follow-up of 60.5 months, the 3-year disease-free survival (DFS) rate was 86%, 90% and 88%, for Arms A, B and C, respectively, while the 3-year overall survival (OS) rate was 96% in all arms. No differences were found in DFS or OS between the combined B and C Arms versus Arm A (DFS: HR = 0.81, 95% CI: 0.59-1.11, P = 0.20; OS: HR = 0.84, 95% CI: 0.55-1.30, P = 0.43). Among the 255 patients who received trastuzumab, 189 patients (74%) completed 1 year of treatment uneventfully. In all arms, the most frequently reported severe adverse events were neutropenia (30% vs. 27% vs. 26%) and leucopenia (12% vs. 13% vs. 12%), while febrile neutropenia occurred in fifty-one patients (6% vs. 4% vs. 5%). Patients in Arm A experienced more often severe pain (P = 0.002), neurological complications (P = 0.004) and allergic reactions (P = 0.004), while patients in Arm B suffered more often from severe skin reactions (P = 0.020).Conclusions: No significant differences in survival between the regimens were found in the present phase III trial. Taxane scheduling influenced the type of severe toxicities. HER2-positive patients demonstrated comparable 3-year DFS and OS rates with those reported in other similar studies.Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12610000151033. © 2014 Fountzilas et al.; licensee BioMed Central Ltd.

Background: Dose-dense sequential chemotherapy including anthracyclines and taxanes has been established in the adjuvant setting of high-risk operable breast cancer. However, the preferable taxane and optimal schedule of administration in a dose-dense regimen have not been defined yet.Methods: From July 2005 to November 2008, 1001 patients (990 eligible) were randomized to receive, every 2 weeks, 3 cycles of epirubicin 110 mg/m2 followed by 3 cycles of paclitaxel 200 mg/m2 followed by 3 cycles of intensified CMF (Arm A; 333 patients), or 3 cycles of epirubicin followed by 3 cycles of CMF, as in Arm A, followed 3 weeks later by 9 weekly cycles of docetaxel 35 mg/m2 (Arm B; 331), or 9 weekly cycles of paclitaxel 80 mg/m2 (Arm C; 326). Trastuzumab was administered for one year to HER2-positive patients post-radiation.Results: At a median follow-up of 60.5 months, the 3-year disease-free survival (DFS) rate was 86%, 90% and 88%, for Arms A, B and C, respectively, while the 3-year overall survival (OS) rate was 96% in all arms. No differences were found in DFS or OS between the combined B and C Arms versus Arm A (DFS: HR = 0.81, 95% CI: 0.59-1.11, P = 0.20; OS: HR = 0.84, 95% CI: 0.55-1.30, P = 0.43). Among the 255 patients who received trastuzumab, 189 patients (74%) completed 1 year of treatment uneventfully. In all arms, the most frequently reported severe adverse events were neutropenia (30% vs. 27% vs. 26%) and leucopenia (12% vs. 13% vs. 12%), while febrile neutropenia occurred in fifty-one patients (6% vs. 4% vs. 5%). Patients in Arm A experienced more often severe pain (P = 0.002), neurological complications (P = 0.004) and allergic reactions (P = 0.004), while patients in Arm B suffered more often from severe skin reactions (P = 0.020).Conclusions: No significant differences in survival between the regimens were found in the present phase III trial. Taxane scheduling influenced the type of severe toxicities. HER2-positive patients demonstrated comparable 3-year DFS and OS rates with those reported in other similar studies.Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12610000151033. © 2014 Fountzilas et al.; licensee BioMed Central Ltd. 14 1

Landmark studies have established taxanes in the treatment of patients with breast cancer; however, recommendations regarding their administration during pregnancy are controversial. The present systematic review aims to synthesize all available data that stem exclusively from breast cancer case series to evaluate the efficacy and safety of taxanes during pregnancy. Overall, 16 studies (50 pregnancies) were eligible for the systematic review according to prisma guidelines. The mean age of patients with breast cancer at pregnancy was 34.6 years. The gestational age (GA) at chemotherapy administration varied from 12 to 36 weeks. The mean GA at delivery was 35.9 weeks. The mean weight of babies at delivery was 2380 g. In 76.7% of cases, a completely healthy neonate was born; in the remaining cases, a neonate who was dystrophic and premature, one with mild hydrocephalus, one with signs of bacterial sepsis, one with hyperbilirubinemia, one with apnea of prematurity, respiratory distress syndrome and gastroesophageal reflux, one with meconium-stained fluid, and another neonate with neutropenia and pyloric stenosis were reported. Ninety percent of children were completely healthy, with a median follow-up of 16 months; in the remaining cases, one child with recurrent otitis media, one with immunoglobulin A deficiency and mild constipation, and another child with delayed speech were reported. In conclusion, available data suggest that taxanes may potentially play a promising role in the optimal therapeutic strategy of patients with breast cancer diagnosed during pregnancy. © 2013 Elsevier Inc.

Background: The mesenchymal-epithelial transition (MET) pathway is frequently altered in tumours. The purpose of our study was to determine the prognostic value of tumour MET expression levels in patients with triple-negative breast cancer (TNBC), in order to strengthen the rationale for targeted therapy of TNBC using MET inhibitors. Methods: We determined expression of MET in formalin-fixed paraffin-embedded surgical specimens of TNBC by immunohistochemistry. Recurrence-free and overall survival was analysed with Cox models adjusted for clinical and pathological factors.Results:Immunostaining for MET was classified as high in 89 of 170 (52%) tumours. MET expression was more frequently observed in G3 carcinomas (P=0.02) but was not significantly associated to any of the other clinical or pathological parameters. High MET expression predicted shorter survival of the patients. Multivariate Cox proportional hazards regression analyses identified MET to be an independent prognostic factor for recurrence (adjusted hazard ratio (HR) for recurrence 3.43; 95% confidence interval (CI) 1.65-7.12; P=0.001) and death (adjusted HR for death 3.74; 95% CI 1.65-8.46; P=0.002). Conclusion: These results provide further evidence that the MET pathway could be exploited as a target for TNBC. © 2013 Cancer Research UK. All rights reserved.

This case control study aims to investigate the role of MMP-2 -1306C > T polymorphism as a potential risk factor and possible prognostic marker for breast cancer in a South European population. 113 consecutive incident cases of histologically confirmed ductal breast cancer and 124 healthy controls were recruited. MMP-2 -1306C > T polymorphism was genotyped; multivariate logistic regression as well as Cox regression analysis were performed. MMP-2 -1306C > T status was not associated with breast cancer risk either at the total sample or at the subanalyses on premenopausal and postmenopausal women. At the survival analysis, a trend towards a favorable association between MMP-2 -1306C > T allele and disease-free survival as well as overall survival was observed. Regarding subanalyses on ER-negative and ER-positive cases, the favorable association implicating MMP-2 -1306C > T allele was particularly evident among ER-positive cases; no significant associations emerged among ER-negative cases. MMP-2 -1306C > T polymorphism does not seem to be a risk factor for breast cancer in South European population; however, a trend towards a favorable association with survival has been observed. © 2013 Springer Science+Business Media Dordrecht.

Pregnancy-associated breast cancer (PABC) is defined as breast cancer occurring anytime during gestation, lactation or within one year after delivery. The optimal management of pregnant women with breast cancer is challenging and not well established; the main concern is the effect of the drugs on the developing fetus and long-term complications after in utero exposure to anti-cancer drugs. Surgical resection is the mainstay of treatment for early breast cancer diagnosed during pregnancy. Modified radical mastectomy is standard of care in first trimester, whereas breast-conserving surgery (lumpectomy with lymph node dissection) can be performed preferably in the second and third trimester. Of note, breast-conserving surgery is not contraindicated per se during the first trimester, but owing to the potential impact of delaying radiotherapy. Radiation therapy is not favored during pregnancy. Moreover, tamoxifen is contraindicated during pregnancy; the agent has been associated with birth defects in up to 20% of exposures. Chemotherapy is generally contraindicated during the first trimester because of the possible damage to organogenesis. Anthracyclines-based regimens are the most widely used is breast cancer treatment and were been shown to be associated with favourable safety profile when administered during pregnancy. As for taxanes, more limited data is available. The use of trastuzumab is contraindicated during pregnancy, given the apparent risk of oligo- and/or anhydramnios as well as the unknown long-term sequelae on the fetus. It is obvious that, diagnosis of breast cancer during pregnancy adds complexity to cancer treatment recommendations. In all cases, a multidisciplinary therapeutic approach among obstetricians, gynaecologists, surgical oncologists, radiation oncologists, medical oncologists, pediatricians and hematologists is clearly warranted © Pioneer Bioscience Publishing Company.

OBJECTIVE: To evaluate breast cancer characteristics in women aged 25 years and younger. METHODS: This was a retrospective, nested, within-cases matched study. The study design was based on a two-phase protocol. In the first phase, stage, grade, histologic subtype, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status were compared between 28 patients (aged 25 years and younger) and 685 older premenopausal women (aged older than 25 years) with breast cancer. The second phase aimed to determine whether young patients exhibited worse prognosis when compared with older premenopausal women. RESULTS: Young patients presented at a more advanced stage (P=.012) and exhibited a higher grade (P=.018). No significant differences were noted regarding histologic subtype, estrogen receptor, and progesterone receptor status. Genetic testing for BRCA1 and BRCA2 mutations was performed in 12 of 28 young patients and mutations were found in 25% of them. Moreover, young women presented poorer overall survival (hazard ratio [HR] 4.30, 95% confidence interval [CI] 1.09-17.03) than their older counterparts, matched by histologic subtype, stage, and grade; a similar pattern was noted regarding relapse-free survival (HR 8.28, 95% CI 2.24-30.60). CONCLUSION: Breast cancer diagnosis in women aged 25 years and younger is uncommon; however, these patients present at a more advanced stage, with a higher grade, and exhibit poorer survival. © 2013 by The American College of Obstetricians and Gynecologists.

Although testosterone therapy is being increasingly prescribed for men, there remain many questions and concerns about testosterone (T) and in particular, T therapy in women. A literature search was performed to elucidate the origin of, and scientific basis behind many of the concerns and assumptions about T and T therapy in women. This paper refutes 10 common myths and misconceptions, and provides evidence to support what is physiologically plausible and scientifically evident: T is the most abundant biologically active female hormone, T is essential for physical and mental health in women, T is not masculinizing, T does not cause hoarseness, T increases scalp hair growth, T is cardiac protective, parenteral T does not adversely affect the liver or increase clotting factors, T is mood stabilizing and does not increase aggression, T is breast protective, and the safety of T therapy in women is under research and being established. Abandoning myths, misconceptions and unfounded concerns about T and T therapy in women will enable physicians to provide evidenced based recommendations and appropriate therapy. © 2012 Elsevier Ireland Ltd.