Christos Markopoulos

National and Kapodistrian University of Athens | uoa · Department of Surgery

This book is a revision companion for the UEMS breast exam. The contents extract and distil the key messages and facts of the exam-linked textbook, published in 2017, giving self-test opportunities at the last chapter. Each chapter starts by listing the key facts at the start. The chapters have been edited by the exam board in collaboration with mo...

The clinical significance of regional nodal status in breast cancer has been well established in breast cancer patients. More specifically, axillary nodal status is a strong prognosticator, next to primary tumor size and grade. Hence, axillary staging remains the standard of care for all breast cancers amenable to curative treatment. Initially, axi...

Background: Hereditary cancer predisposition syndromes are responsible for approximately 5–10% of all diagnosed cancer cases. In order to identify individuals at risk in a cost-efficient manner, family members of individuals carrying pathogenic alterations are tested only for the specific variant that was identified in their carrier relative. The p...

Background/aim: Germline copy number variation (CNV) is a type of genetic variant that predisposes significantly to inherited cancers. Today, next-generation sequencing (NGS) technologies have contributed to multi gene panel analysis in clinical practice. Materials and methods: A total of 2,163 patients were screened for cancer susceptibility, u...

533 Background: Gene-expression profiling tests (e.g. Oncotype, Mammaprint, Prosignia, Breast Cancer Index and EndoPredict) are widely used in the care of patients with early-stage hormone positive breast cancer (node negative or 1-3 lymph nodes). However, these tests are resource intensive, and few studies have compared their value with either fre...

509 Background: Individual risk assessment of distant recurrence (DR) is particularly relevant for early-stage HR+ breast cancer patients, as they face a prolonged risk of recurrence even after adjuvant endocrine therapy. Previously, we have shown that the Breast Cancer Index (BCI) and BCIN+ risk groups are significantly prognostic for risk of over...

Background: Women with HR+ breast cancer experience a persistent risk of distant recurrence (DR) even after completion of 5 years of adjuvant endocrine therapy, with more than 50% of DR occurring after 5 years (late DR). The prognostic genomic signatures currently being used in the clinic were not developed or optimized specifically for late DR. We...

AIM: The majority of invasive lobular carcinomas (ILC) of the breast are luminal A tumors of good prognosis, having a low or intermediate OncotypeDX Recurrence Score (RS). They are usually treated with hormonal therapy only and some have doubted the relevance of the RS for patients with ILC. However, in a number of ILC cases a high RS can be found,...

AIM: Most patients tested by a 44-gene panel for hereditary cancer (HerediGene), even though they had a strong family history, have a negative result or a finding in a low-risk gene. This creates a question about the risk for these individuals to develop breast cancer. The Polygenic Risk Score is a tool used to identify and calculate the lifetime r...

Cancer patients’ quality of life (QoL) and distress are affected by dispositional factors such as attachment anxiety or avoidance. In this review, we aimed to provide a thorough overview of the relationship between attachment dimensions and QoL and distress among early-stage breast cancer patients. Following PRISMA guidelines, we conducted a system...

Background: Dose-dense sequential chemotherapy with anthracyclines and taxanes achieved an 18% reduction of recurrence risk in early breast cancer (BC). The optimal chemotherapy schedule and interval between cycles remain under investigation. Methods: Overall, 990 patients were randomised to receive either three cycles of epirubicin (E, 110 mg/m...

Novel HER2-directed antibody-drug conjugates (ADC) have demonstrated efficacy in HER2-low expressing breast cancers, which are currently defined as those with IHC scores of 1+ or 2+ with a negative ISH assay. However, current HER2 testing methods are designed to identify HER2 amplified tumors with “high” expression levels. The true definition of “H...

Introduction Decision making in surgical oncology of the breast has increased its complexity over the last twenty years. This Delphi survey investigates the opinion of an expert panel about the decision making process in surgical procedures on the breast for oncological purposes. Methods Twenty-seven experts were invited to partake into a Delphi S...

Background: Dose-dense sequential chemotherapy based on anthracyclines and taxanes has achieved an 18% reduction of recurrence risk in the adjuvant setting of early breast cancer (BC). However, the optimal chemotherapy schedule and the preferable interval between cycles are still under investigation. Methods: A total of 990 eligible BC patients wer...

Background: Breast cancer is the most frequently diagnosed cancer in women and about 10% of breast cancer cases are hereditary. BRCA1 and BRCA2 are the genes most frequently associated with Hereditary Breast Cancer, although there are numerous other genes, such as PALB2, CHEK2 and ATM, that require to be considered as well. Germline Copy Number Var...

Background/aim: The use of multi-gene panels for germline testing in breast cancer enables the estimation of cancer risk and guides risk-reducing management options. The aim of this study was to present data that demonstrate the different levels of actionability for multi-gene panels used in genetic testing of breast cancer patients and their fami...

The clinical management of invasive breast cancer has changed during the last decade with the use of molecular-based multigene assays (MGAs).They are increasingly used to gain additional prognostic and predictive information and guide adjuvant treatment decisions. Since 2004, several MGAs have become available but, four of them are the most widely...

Sentinel lymph node biopsy (SLNB) remains the gold standard for regional axillary staging in early, clinically and radiologically node-negative breast cancer. The technique of SLNB has been refined since its initial conception, and currently SLNB is a milestone of breast cancer surgical management. Cumulative evidence from randomized trials suggest...

Multiparametric assays for risk stratification are widely used in the management of both node negative and node positive hormone receptor positive invasive breast cancer. Recent data from multiple sources suggests that different tests may provide different risk estimates at the individual patient level. The TEAM pathology study consists of 3284 pos...

Introduction The main hormonal treatment of estrogen sensitive breast cancer includes the use of selective estrogen receptor modulators, aromatase inhibitors and GnRH-Analogs. It has been observed that administering aromatase inhibitor to breast cancer patients not only impairs their glucose metabolism but it can even cause frank diabetes mellitus....

Background Tumor-infiltrating lymphocytes (TILs) and their subsets contribute to breast cancer prognosis. We investigated the prognostic impact of CD3+, CD8+ and FOXP3+ TILs in patients with early intermediate/high-risk breast cancer treated with adjuvant anthracycline-based chemotherapy within two randomized trials conducted by our Group.Methods W...

PURPOSE Most distant recurrences (DRs) in women with hormone receptor–positive breast cancer occur after 5 years from diagnosis. The Clinical Treatment Score post-5 years (CTS5) estimates DRs after 5 years of adjuvant endocrine therapy (AET). The aim of this study was to externally validate the CTS5 as a prognostic/predictive tool. METHODS The CTS...

e12534 Background: The purpose of this analysis is to evaluate how many patients previously treated according to OncotypeDX Recurrence Score (RS) could have been spared of Chemotherapy if the TAILORx RS data had been taken into account in the clinical treatment decisions. Methods: A series of 182 patients, 34-74 years of age with early breast cance...

Ductal cancer in situ (DCIS) is mainly a screen-detected disease and although the risk for breast cancer is age-dependent, most screening programs do not include women over the age of 75 years. Older women are usually excluded from clinical trials and treatment practices are largely based on observational studies or extrapolation of trial results f...

The Breast Surgery theoretical and practical knowledge curriculum comprehensively describes the knowledge and skills expected of a fully trained surgeon practicing in the European Union and European Economic Area (EEA). It forms part of a range of factors that contribute to the delivery of high quality cancer care. It has been developed by a panel...

Executive summary The Breast Surgery theoretical and practical knowledge curriculum comprehensively describes the knowledge and skills expected of a fully trained breast surgeon practicing in the European Union and European Economic Area (EEA). It forms part of a range of factors that contribute to the delivery of high quality cancer care. It has b...

Background: EUSOMA undertook the commitment of defining the requirements for a specialist breast centre, which has become the reference document for the implementation of breast centres. Summary: The EUSOMA requirements for a specialist breast centre give clear indications regarding the requisite caseload, dedicated team composition (core and no...

Background The application of the Next Generation Sequencing (NGS) technology has facilitated multigene panel testing for hereditary breast cancer (BC) in clinical practice. We performed a retrospective analysis of individuals referred for testing in our lab aiming to investigate the contribution of included genes and evaluate current genetic testi...

Multigene assays (MGAs) guide treatment in early-stage breast cancer (ESBC) enabling selective and effective use of adjuvant chemotherapy (CT). Support for all MGAs had previously been derived from retrospectively-analyzed, prospective studies. Only 2 ESBC MGAs, the 70-gene signature (MammaPrint®) and the 21-gene Recurrence Score (RS) assay (Oncoty...

The primary treatment modality for breast cancer is surgery, which is a craft specialty requiring lengthy, high-quality training to achieve competency. This is especially true in an era of complex multidisciplinary oncology regimes and oncoplastic and reconstructive surgeries. Globally, training in breast surgery is highly variable in length, conte...

Caregivers delivering care to breast cancer patients wish to provide the highest quality breast care possible. Due to the complexity of the care pathway, this care should be delivered by a multidisciplinary team working in a breast cancer unit/centre. This book was written by experts from different disciplines and presents ideas for developing a br...

Background: Hereditary cancer predisposition syndromes are responsible for approximately 5-10% of all diagnosed cancer cases. In the past, single-gene analysis of specific high risk genes was used for the determination of the genetic cause of cancer heritability in certain families. The application of Next Generation Sequencing (NGS) technology ha...

BACKGOUND: Hereditary cancer predisposition syndromes are believed to be responsible for approximately 5-10% of all diagnosed cancer cases. In the past, single genes analysis of certain high risk genes was used for the determination of the genetic cause of cancer heritability in certain families. The selection of genes was mainly based on the famil...

Introduction: Vascularized tissue transfers based on perforator vessels have been proven to be reliable and versatile reconstructive procedures. In upper chest, such surgical procedures provide efficient post tumor extirpation or trauma defect reconstruction as well as improved aesthetic and quality of life outcomes. In this study the anatomic char...

Biomarkers lie at the heart of precision medicine. Surprisingly, while rapid genomic profiling is becoming ubiquitous, the development of biomarkers usually involves the application of bespoke techniques that cannot be directly applied to other datasets. There is an urgent need for a systematic methodology to create biologically-interpretable molec...

Several studies support an important role of angiogenesis in breast cancer growth and metastasis. The main objectives of the study were to investigate the immunohistochemical expression of vascular endothelial growth factor (VEGF) family ligands (VEGF-A and VEGF-C) and receptors (VEGFR1, VEGFR2 and VEGFR3) in breast cancer and their associations wi...

Hazard ratios (95% CIs) estimated from univariate Cox regression for selected clinicopathological parameters. (PDF)

Descriptive statistics for the five angiogenesis-related proteins (calculated as the percentage of tumor stained cells). (PDF)

Associations between the angiogenesis-related proteins (using 5-years ROC curve cut-offs) and selected clinicopathological parameters. Data presented as N (%). p-values of the chi-square test are shown. (PDF)

Associations among the angiogenesis-related proteins (using 5-years ROC curve cut-offs). Data presented as N (%). p-values of the chi-square test are shown. (PDF)

Aim: Due to increasing life expectancy, patients with breast cancer remain at risk of dying due to breast cancer over a long time. This study aims to assess the impact of age on breast cancer mortality and other cause mortality 10 years after diagnosis. Methods: Postmenopausal patients with hormone-receptor positive breast cancer were included i...

Background: Aromatase inhibitors improve disease-free survival compared with tamoxifen in postmenopausal women with hormone receptor-positive breast cancer. The Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial compared exemestane monotherapy with sequential therapy of tamoxifen followed by exemestane. The trial failed to show a statist...

Biomarkers lie at the heart of precision medicine, biodiversity monitoring, agricultural pathogen detection, amongst others. Surprisingly, while rapid genomic profiling is becoming ubiquitous, the development of biomarkers almost always involves the application of bespoke techniques that cannot be directly applied to other datasets. There is an urg...

Histological grade remains an independent predictor of outcome for invasive breast cancer. The internationally accepted standard grading system is the Elston and Ellis grading system based on a local hospital (Nottingham) cohort treated between 1951-1973. Histological grade, with nodal status, tumour size and receptor measurements (ER, PgR, HER2) g...

Multiparametric assays for risk are increasingly used in the management of node-negative and node-positive hormone receptor-positive invasive breast cancer. Data from multiple sources suggests different tests may provide different risk estimates at the individual patient level¹. Analysis from the TEAM pathology study (Bayani and Yao et al npjBreast...

Large-scale sequencing initiatives have revealed a wealth of common and novel variants as well as copy-number aberrations, across different malignancies. This growing list of variants/aberrations can sometimes be matched to specific therapeutics. Such “actionable mutations/changes” hold promise for personalized treatment in the future, with treatme...

Hormone receptor positive breast cancer remains an ongoing therapeutic challenge. Despite optimal anti-endocrine therapies, most breast cancer deaths follow a diagnosis of early luminal cancer. Data describing molecular events in breast cancer has yet to be translated into actionable information to inform medical management and benefit patients. To...

This textbook provides a comprehensive overview of the state of the art knowledge of breast cancer management for the modern breast surgeon. It covers all aspects of multidisciplinary care including primary breast and axillary surgery, reconstruction and oncoplastic techniques, external beam radiotherapy and newer techniques such as tomotherapy, in...

Breast surgery is associated with specific complications which, despite not being life-threatening, can compromise quality of life, increase costs and delay the administration of adjuvant treatment. They are related to the division of blood vessels, nerves and lymphatics, infection, seroma and scar tissue formation. Breast surgery-specific complica...

The clinical management of invasive breast cancer has changed dramatically in the last decade with the increasing use of multigene assays (MGAs) for guiding adjuvant treatment decisions. MGAs differ in terms of the technological platform used, the specific genes assessed and the patient populations in which they were developed and validated. This c...

The European Board of Surgery Qualification (EBSQ) Examination in Breast Surgery is organised by the UEMS-EBS Division of Breast Surgery and consists of two parts: Part A (written part) and Part B (oral part) (► https://www.uemssurg.org/divisions/breast-surgery/ebsq-examination). A candidate has to «pass» both parts in order to be qualified for the...

BACKGROUND: Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with...

Many women with hormone receptor-positive early breast cancer can be managed effectively with endocrine therapies alone. However, additional systemic chemotherapy treatment is necessary for others. The clinical challenges in managing high-risk women are to identify existing and novel druggable targets, and to identify those who would benefit from t...

In primary breast cancer, sentinel lymph node biopsy has been established as the gold standard for regional axillary staging. A robust body of randomized data support its accuracy and safety in patients with early, clinically node negative disease. However, the role of SLNB remains debatable in various patient subgroups, and recent advances in hist...

Germline mutations in the BRCA1 and BRCA2 genes are associated with hereditary predisposition to breast and ovarian cancer. Sensitive and accurate detection of BRCA1 and BRCA2 mutations is crucial for personalized clinical management of individuals affected by breast or ovarian cancer, and for the identification of at-risk healthy relatives. We per...

Background: Prevention of bone metastases is a major issue for breast cancer patients, as it would improve quality of life in a population where long survival is anticipated. Patients and methods: Early breast cancer patients, who had been treated with anthracycline-based chemotherapy within two randomized trials, were included in the study. We...

Background After 5 years of median follow-up, the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial reported no difference in disease-free survival between exemestane monotherapy and a sequential scheme of tamoxifen followed by exemestane in postmenopausal patients with early-stage, hormone receptor-positive breast cancer. As recurrence risk...