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

[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

[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.]

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

[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.]

All articles in the issue

Related contents


[Forgotten agent: raloxifene]


[The largest group of the patients with osteoporosis is postmenopausal women characterized by a state of menopausal hormone deficiency which is results in accelerated bone loss. This increased bone resorption significantly elevates the risk of bone fractures including the most common type, i.e. vertebral fractures. In addition to the increased risk of fractures, estrogen deficiency affects other organs, thus, increasing the incidence of cardiovascular diseases, cancers, mood disorders and the symptoms of menopausal syndrome in women after menopause. In postmenopausal osteoporosis, the primary objective is to maintain the existing bone mass, a priority for the prevention and treatment of bone fractures. Hormone deficiency may be prevented by the administration of estrogen but the treatment may have adverse effects such as increased risk of endometrial cancer. An etiological therapy is desirable where the compound used for treatment exerts effects similar to that of estrogen to prevent postmenopausal bone loss as well as reduces the risk of cardiovascular disease without the stimulation of reproductive tissues.]

Clinical Neuroscience

[Prognostic significance of invasion in glioblastoma]


[Glioblastoma is the most common malignant CNS tumor, its surgical removal is hindered by the tumors invasive nature, while current anti-tumor therapies show limited effectiveness – mean overall survival is 16-24 months. Some patients show minimal response towards standard oncotherapy, however there are no routinely available prognostic and predictive markers in clinical practice to identify the background of mentioned differences in prognosis. This research aims to identify the prognostic significance of invasion-related extracellular (ECM) components. Patient groups with different prognoses were created (OS: group A <16 months, group B > 16 months), and internationally recognized prognostic markers (IDH1 mutation and MGMT promoter hyper-methylation) were tested in the flash-frozen tumor samples. Furthermore, the mRNA levels of 46 invasion-related ECM molecules were measured. Clinical data of the patients who have been operated on at the University of Debrecen Clinical Center Department of Neurosurgery and treated at the Department of Clinical Oncology showed no significant differences except for survival data (OS and PFS), and reoperation rate. All samples were IDH wild type. MGMT promoter hypermethylation rate showed significant differences (28.6% vs 68.8%). The expressional pattern of the invasion-related ECM molecules, i.e. the invasion spectrum also showed major differences, integrin β2, cadherin-12, FLT4/VEGFR-3 and versican molecules having signficantly different mRNA levels. The accuracy of the inivasion spectrum was tested by statistical classifier, 83.3% of the samples was sorted correctly, PPV was 0.93. The difference found in the reoperation rate when comparing different prognostic groups aligns with literature data. MGMG promoter region methylation data in Hungarian samples has not been published yet, and further confirming current knowledge urges the implementation of MGMT promoter analysis in clinical practice. Studying the invasion spectrum provides extra information on tumors, as a prognostic marker it helps recognizing more aggressive tumors, and calls attention to the necessity of using anti-invasive agents in GBM therapies in the future.]

Lege Artis Medicinae

[The clinical importance of HER2 expression in breast cancer]

KAHÁN Zsuzsanna

[HER2 (neu/c-erbB-2) is a member of the EGF receptor family. It is activated without binding a specific ligand that leads to malignant transformation and tumor progression. Overexpression of HER2 is detected in approximately one quarter of human breast cancers. Immunohistochemistry and in situ hybridization (FISH) are the most widely used techniques in studying HER2 expression. HER2 positivity indicates worse outcome in node positive breast cancer and increasing number of studies show unfavourable prognosis in node negative cases as well. Recent data indicate that the knowledge of HER2 status may promote therapeutic decision. The generally applied cyclophosphamide- methotrexate-5-fluorouracil (CMF) polychemotherapy seems to provide no benefit in HER2 positive cases in contrast with HER2 negative breast cancer patients. Interestingly, doseintensive doxorubicin based chemotherapy gives better results in HER2 positive than in HER2 negative tumors. Determination of HER2 expression has great importance before therapeutic application of the humanized antibody trastuzumab (Herceptin). HER2 overexpression usually correlates well with estrogen and progesterone receptor negativity and hormone-resistance, therefore hormonal therapy is not justified for these patients. Some experimental and clinical data indicate that in case of simultaneous HER2 and ER positivity tamoxifen worsens treatment results which may be prevented by the coadministration of tamoxifen and trastuzumab. Emerging experimental and clinical data about HER2 has led to a new stage of individual treatment of breast cancer patients. The knowledge of HER2 status promotes antitumor intervention based on molecular characteristics of breast cancers. Therefore, reliable HER2 tests are needed in the everyday practice.]

Hungarian Radiology

[Results of non-operative pathological breast diagnostics - One year experience at the Bács-Kiskun County Teaching Hospital]


[INTRODUCTION - Non-operative cytological and histopathological assessment of breast lesions are part of the triple (physical, imaging and pathologic) diagnostic approach and allow a more precise planning of surgical procedures. Both methods have advantages and disadvantages; currently, core biopsy is believed to be more efficient in reaching the diagnostic target. PATIENTS AND METHODS - Breast specimens with a histological diagnosis at the Department of Pathology of the Bács-Kiskun County Teaching Hospital were analysed for their preoperative pathology, using the conventional C1-5 and B1-5 diagnostic categories. RESULTS - 295 cytology and 130 core needle biopsy cases were analysed. The rate of non diagnostic (C1 and B1) material was higher for cytology (0.18 versus 0.08 in general; 0.09 versus 0.01 for malignant cases). The rate of cases with an uncertain diagnostic category (C3 and C4 or B3 and B4) was also higher for the cytology specimens (0.24 versus 0.07). False-negative and false-positive cases were rare, but still more frequent among cytology specimens. CONCLUSION - Core needle biopsy performs better than fine needle aspiration cytology in the establishment of a nonoperative diagnosis at our institution. Despite these results, cytology continues to be the first diagnostic choice, because of its relatively low costs.]

Lege Artis Medicinae

[Diagnostic algorythm and treatment of bilateral malignant histiocytoma in everyday medical practice?]

VANYA Melinda, SZILI Károly, KELLERMAN Péter, KISS János, KAISER László, LAJOS György

[OBJECTIVE - We report the rare case of a 47-year-old man with malignant fibrous histiocytoma, developing in the right tibia. CASE REPORT - We report a case of a 47 year-old man with chronic pain in his right leg. Magnetic resonance imaging and biopsy was performed. His pathological result was malignant fibrous histiocytoma. CONCLUSIONS - The management of malignant fibrous histiocytoma contains the combination of surgical procedure, chemotherapy and radiotherapy. The diagnosis and the total removal of the tumour is very difficult. ]