Clinical Oncology

[Practical use of meta-analyses in predicting disease risk, outcome, and therapy response in breast cancer]

MENYHÁRT Otília1,2, GYŐRFFY Balázs1,2

FEBRUARY 20, 2019

Clinical Oncology - 2019;6(01)

[Breast cancer is globally the most frequent malignant disease in women with increasing incidence. Meta-analyses using data from a large set of patients combining genetic and standard clinicopathological features provide valuable models in predicting disease risk, outcome and therapy response. With the advent of molecular technologies, the amount of available data generated for each tumor and each patient is growing exponentially. The increased data availability allows the development of new innovative systems enabling to discover more effective prognostic and predictive biomarkers. The goal of this review is to summarize meta-analyses that utilize data from countless patients to provide breast cancer risk prediction (Gail-model, Claus-model, BRCApro, IBIS, BOADICEA), and prediction of prognosis and expected therapy response (PREDICT, Magee). In the last part of the review we introduce online analytical tools (KMplot, ROCplot) developed to examine, rank and validate new prognostic and predictive biomarker candidates.]


  1. Semmelweis Egyetem, II. Sz. Gyermekgyógyászati Klinika, Budapest
  2. MTA TTK, Lendület Onkológiai Biomarker Kutatócsoport, Budapest



Further articles in this publication

Clinical Oncology

[Practical use of meta-analyses in predicting disease risk, outcome, and therapy response in breast cancer]

KAHÁN Zsuzsanna, TARI Gergely, ENYEDI Márton, HARACSKA Lajos

[Germinal BRCA status infl uences patient care both in early and advanced/metastatic breast cancer. Ideally, the patient should make the decision on the type of surgery or the avoidance of radiotherapy being aware of the BRCA status; based on the most recent clinical studies, this knowledge may infl uence the type of chemotherapy in the neoadjuvant, adjuvant, or metastatic setting or may raise the use of emerging targeted therapies. DNA-targeting cytostatic agents, mostly platinum agents and PARP inhibitors that act by inducing synthetic lethality, provide specifi c therapies in BRCA-mutant cases. The optimum place and sequence of these specifi c agents in treatment, however, are not known yet. International guidelines promote BRCA testing for the specifi cation of treatment strategy in all HER2-negative advanced/metastatic breast cancer cases (NCCN) or at least in all cases when, based on certain predictors, the presence of mutations is likely (ESMO). Recently, the methods employed for BRCA testing have improved immensely and are widely available through the services of various providers. For the identifi cation of the mutation, sequencing of the whole genes is needed, which can be achieved faster and more cost-effi ciently using next-generation sequencing (NGS) platforms compared to previous methods. It is the responsibility of the physician to consider the possibility of BRCA mutations and to raise the issue of BRCA testing to the patient if the family history, the age, previous malignant disease(s) of the patient, or the cancer features are suggestive of genetic risk.]

Clinical Oncology

[The role of the microbiome in the etiology and treatment of neoplastic diseases]

SCHWAB Richárd, BACSUR Emese, TORDAI Attila, PETÁK István

[Experimental data on the role of the microbiome in the onset and progression of infl ammatory diseases and cancer have been accumulated for years. An important milestone in this respect was the discovery that APC mutant mice in sterile conditions do not develop colon cancer of the FAP type. The direct role of the Enterobacteriaceae and Fusobacteriaceae bacterial families were also shown in the pathomechanism of the same experimental model. The toxic effect of chemotherapy on the gut fl ora has been well documented, but it may very well be that this putative side effect is part of the effi cacy, primarily in the case of adjuvant chemotherapy. The fi rst reproducible methods of microbiome molecular diagnostics are already available today. In addition to standard large clinical studies, we can increasingly rely on evidence of molecular pathomechanism and „real-world” clinical experience in the clinical interpretation of the microbiome. The overview summarizes the results of the fi eld research and its translation possibilities in terms of routine clinical practice.]

Clinical Oncology

[Molecular subtypes and the evolution of treatment decisions in metastatic colorectal cancer]

RODRIGO Dienstmann, RAMON Salazar, JOSEP Tabernero

[Colorectal cancer (CRC) has clinically-relevant molecular heterogeneity at multiple levels: genomics, epigenomics, transcriptomics and microenvironment features. Genomic events acquired during carcinogenesis remain drivers of cancer progression in the metastatic setting. For example, KRAS and NRAS mutations defi ne a population refractory to EGFR monoclonal antibodies, BRAFV600E mutations associate with poor outcome under standard therapies and response to targeted inhibitors in combinations, while HER2 amplifi cations confer unique sensitivity to double HER2 blockade. Multiple rare gene alterations driving resistance to EGFR monoclonal antibodies have been described with signifi cant overlap in primary and acquired mechanisms, in line with a clonal selection process. In this context, sequential analysis of circulating tumor DNA has the potential to guide drug development in a treatment refractory setting. Rare kinase fusion events and complex alterations in genes involved in DNA damage repair have been described, with emerging evidence for targetability. On the other hand, transcriptomic subtypes and pathway activation signatures have also shown prognostic and potential predictive value in metastatic CRC. These markers refl ect stromal and immune microenvironment interactions with cancer cells. For example, the microsatellite instable (MSI) or POLE ultramutant CRC population is particularly sensitive to immune checkpoint inhibitors, while tumors with a mesenchymal phenotype are characterized by activation of immunosuppressive molecules that mandate stratifi ed development of novel immunotherapy combinations. In this manuscript we review the expanding landscape of targetable oncogenic alterations and signatures in metastatic CRC and discuss the clinical implementation of novel molecular diagnostic tests.]

Clinical Oncology

[P53 – the suppressor]


[Our basic nature requere cells quantity and quality to perform differenciate activity. p53 has the responsibility for quick out those cells who carries molecular failures in DNA avoiding transfer mutations into doughter cells. If the DNA-repair insuffi cient p53s with on apoptosis. Whe p53 is mutated the phenotypes are different in a wide range due to the heterogenity of the DNA damages, and also the expression pattern of a suppressor protein. With the increasing amout the damaged DNA the genomic instability elevates D the risk to development of tumors. It is linict mutated gene could be a promosing tr, 10t for therapy. So far the attempts have little value for the clinic.]

Clinical Oncology

[The role of artifi cial intelligence in precision medicine]

MESKÓ Bertalan

[The essence of practicing medicine has been obtaining as much data about the patient’s health or disease as possible and making decisions based on that. Physicians have had to rely on their experience, judgement, and problem-solving skills while using rudimentary tools and limited resources. With the cultural transformation called digital health, disruptive technologies have started to make advanced methods available not only to medical professionals but also to their patients. These technologies such as genomics, biotechnology, wearable sensors, or artifi cial intelligence (AI) are gradually leading to three major directions. They have been (1) making patients the point-of-care; (2) created a vast amount of data that require advanced analytics; and (3) made the foundation of precision medicine. Instead of developing treatments for populations and making the same medical decisions based on a few similar physical characteristics among patients, medicine has shifted toward prevention, personalization, and precision. In this shift and cultural transformation, AI is the key technology that can bring this opportunity to everyday practice.]

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Related contents

Lege Artis Medicinae

[Complex pathological diagnosis of breast cancer and the patient care based on it over the past 20 years]


[The diagnosis of breast cancer has become more complex in the past 20 years. Intraoperative diagnosis has been mostly replaced by multidisciplinary preoperative/ nonoperative diagnostics. Surgical treatment can be planned in advance for the breast as well as for the axilla. In many cases, routinely performed radical surgery has been replaced by selectively applied, less radical, conservative operations (sectoral or wide local excisions, sentinel lymph node biopsy) that are suitable for smaller tumours mostly detected by screening. In addition to prognostic markers listed in the pathology reports (lymph node status, tumour size, vascular invasion, status of resection margins), an increasing emphasis has been placed on predictive markers (estrogen receptors, progesterone receptors, HER-2, basal and proliferation markers) that allow molecular typing of breast carcinomas and that mostly influence systemic treatment. Tools to predict the efficiency of treatment have become increasingly available, and these might also help in planning neoadjuvant therapies, a modality which has also been introduced in the past 20 years. The present article gives a brief, subjective, thematic insight into some of these changes, selected on the basis of their relation to the pathological diagnosis of breast carcinoma.]

Clinical Oncology

[Clinical role of multigenic prognostic tests in breast cancer therapy]


[Current clinical practice for breast cancer originates in “evidence based medicine”. In this, each tumor receives a therapy optimal for a given patient population - which might not be optimal for each individual patient. Multigenic tests determining expression of a set of genes can provide additional support in this decision process. Two such tests (MammaPrint and Prosigna) have already received FDA clearance. A number of additional test are commercially available (IHC4, Oncotype DX, EndoPredict, BCI). A common property of these assays is their utility in estrogen receptor positive early breast cancer. The main clinical problem answered by them is the necessity of adjuvant chemotherapy. To date, no reliable algorithm has been identifi ed capable to pinpoint the most effective chemotherapy combination for a given patient. Furthermore, there is no trustworthy test for triple negative breast cancer. The assays utilize different technologies (immunohistochemistry, gene chips, RT-PCR) and a discrepant list of genes - these result in discordance of the predictions for the individual patient. Despite these shortcomings, multigenic tests quickly gained foothold in breast cancer therapy decision process. Their utility is supported by the cost reduction for the health care providers by lowering the number of patients eligible for chemotherapy.]

Hungarian Radiology

[Results of breast cancer screening and clinical mammography at the Kenezy Breast Center, Debrecen between 2002-2003]


[INTRODUCTION - Breast cancer screening has been started in January 1. 2002. in Hungary in the course of the National Health Program. Breast cancer is the main cause of death among women’s malignant tomors, and the aim of the project is to reduce this mortality. The chance of survival is highly increased by the early detection of the disease. Kenezy Breast Center was connected to this project. PATIENTS AND METHODES - Females between 45-65 years without symptoms participated in the project. Paralel to this women with symptoms, sometimes with palplable masses were clinically examined. Screening mammography films were read by two radiologists and the complementary examinations of the breast and the axillary lymph nodes - ultrasonography, guided biopsy (FNAB, core biopsy) - were performed always by the same doctor. Results of the two projects were compared. RESULTS - The incidence of malignant breast cancer was 4‰ in the screening and 1,5% in the clinical group. 46.5% of the malignant breast cancers revealed by the clinical examinations was diagnosed in the group of women between the age of 45 to 65 years. This is the age when most women are involved in the screening program. 7.3% of the tumors was diagnosed in the 40- 44 year age-group and 11.3% among women aging 66-77 years. The rate of malignant tumors smaller than 1.5 cm was 49.1% according to screening records and 36% in the clinical trial. In both groups, tumor size of 1.5 cm proved to be a critical limit regarding to the development of metastases, mainly in the axillary region. Above this size, metastases were more frequent. CONCLUSIONS - Both breast screening program and clinical exams are of great significance. Based on the data obtained during two years, authors found that women below the age of 40 and above the age of 65 should also be involved in the screening program. Detection of breast tumor is possible at an early stage by screening. In the case of small tumors (smaller than 1.5 cm) the development of axillary metastases is less likely than in the case of larger ones. The lack of metastases in the axillary lymph nodes offers better prognosis according to the published scientific data, which reinforces the importance and necessity of the screening programs.]

Lege Artis Medicinae

[Changing tendencies in retinal surgery]


[Retinal detachment, a disease caused by pathologic alteration of the vitreoretinal relationship, may decrease vision to blindness without treatment. Although some of the patients with retinal detachment become blind for the time being, last two decades produced significant improvement both in diagnosis and treatment. As a result of new surgical techniques we can perform successful surgery even in cases that were earlier inoperable. Recent methods are significantly less traumatic to the eye than they were 20 years ago. Dramatically reduced bedrest before and after surgery, regional or even topical anaesthesia instead of general anaesthesia, short term hospitalisation or one day surgery, short term restriction of physical activity after surgery are the most important consequences of the new wave of retinal detachment repair. According to recent recommendations of the prophylactic treatment of peripheral retinal lesions we treat only horse tears with sudden retinal complaints.]

Clinical Neuroscience

[Relationship between the efficacy of atypical antipsychotics and polymorphism of dopamine D3 receptor in schizophrenia]

SZEKERES György, JUHÁSZ Anna, KÉRI Szabolcs, RIMANÓCZY Ágnes, SZENDI István, SZABÓ Zoltán, JANKA Zoltán

[Object - Numerous relevant variants of dopamine receptors have been identified in schizophrenia. The Ser9Gly gene polymorphism of dopamine D3 receptor is known as a susceptibility factor for the disease. In addition, it has a role in the modification of therapeutic effect of antipsychotics. In this naturalistic study the authors investigated the relationship between this polymorphism and the therapeutic response to atypical antipsychotics. Method - 75 patients with schizophrenia according to DSM-IV and 45 healthy controlls were recruited. The patients were divided to responder and nonresponder subgroups, cut-off: >20 point improvement in Global Assessment of Functioning. By polymerase chain reaction the genotype of dopamine D3 receptor of every participant was determined. Results - The Ser9Ser genotype of dopamine D3 receptor was more frequent in the nonresponder subgroup (64%, p=0.0018). The Ser9 allele was overrepresented among nonresponder patients (82%, p=0.0172). Conclusion - Based on our results, the worse therapeutic response to atypical antipsychotics is associated with Ser9 variant of dopamine D3 receptor.]