Predictive markers in breast cancer

04/2021 MUDr. Zuzana Bielčiková, Ph.D.
Prognostic and predictive markers are the way to the treatment personalization. Prediction of prognosis is important for stratifying the disease according to the risk of relapse and is a prerequisite for escalation or de-escalation of treatment. In the case of early hormone-sensitive (HR+) breast cancer, multigene assays (MGA) in particular fulfil this role. There are also hopes for the prognostic significance of proliferation activity of the disease (Ki 67) in response to neoadjuvant hormonal therapy. For aggressive subtypes (human epidermal growth factor receptor 2 - positive [HER2+] and triple negative breast cancer [TNBC]), main prognostic markers are the achievement of pathological complete remission and the presence of tumor infiltrating lymphocytes, programmed death ligand 1 (PD L1) also stayed in this category. The only and already established predictive markers of therapy response in early breast cancer remain the estrogen receptor (ER) and HER2. We're slightly better at predicting of therapy response in metastatic breast cancer; to ER and HER2 we can add PD L1 in metastatic TNBC, a mutation in the PIK3CA gene in HR+ cancer, and the presence of mutations in BRCA genes as predictors for inhibitors of PARP Prediction of therapeutic effect is also a prerequisite for improving patient survival and for reducing the toxicity of non-target treatment.

Inhibitors of the cycline‑dependent kinases 4/6 in the treatment of patients with breast cancer

04/2021 MUDr. Marta Krásenská
Hormone receptor positive breast cancers are characterized by the presence of receptors for estrogen and/or progesterone and represent up to 75 %. Endocrine therapy is effective in neoadjuvant and adjuvant setting and remains the basic treatment modality for advanced disease. Up to half of patients with metastatic disease develop resistance to endocrine therapy. In order to modify the development of resistance to endocrine therapy, inhibitors of the cyclin-dependent kinases 4/6 have been developed. Palbociclib, ribociclib and abemaciclib have shown statistically and clinically significant efficacy in many III phase clinical trials. Consistently, they almost double progression free survival, increase the overall response rates, and prolong patient survival. In combination with an aromatase inhibitor and fulvestrant, they have become the new standard for first and second line treatment of hormone receptor positive metastatic breast cancer.

Triple negative breast cancer

04/2021 MUDr. Michaela Miškovičová, Ph.D.
Triple negative breast cancer (TNBC) represents a heterogeneous group of breast cancers, histologically, molecularly biologically and immunologically. A common molecular feature is that they do not express alpha estrogen, progesterone, and HER2 receptors.1 They appear to be the most aggressive subtype of breast cancer and are usually associated with a serious prognosis and increased mortality worldwide. Their extremely high proliferation and tendency to hematogenous metastasis are typical.2 The severity of this disease is primarily observed in younger women but can occur in all age groups. Epidemiologically, they represent about 15-20 % of newly diagnosed breast cancers.3 Young patients often suffer from worse clinical outcomes, such as early relapse and the appearance of visceral metastases. Current clinical treatment of TNBC is generally challenging, with chemoresistance and recurrent tumor recurrence being common barriers.4
We have seen little therapeutic progress in recent decades, and chemotherapy remains the standard of care. Although the incorporation of targeting agents such as poly (ADP ribose polymerase (PARP) inhibitors and immune checkpoint inhibitors in clinical practice appears promising, TNBC responses to these therapies still vary widely. However, despite enriched chemosensitivity and immunogenicity, most patients with TNBC do not achieve satisfactory clinical responses. The lack of specific effective therapeutic targets is one of the key factors preventing a significant improvement in the effect of targeted treatment.5 Incorporating immunomolecular targets into combination and improving standard chemotherapy, especially in the early stages of the disease, may be key to unlocking the promising future of management of TNBC.4

Radiotherapy in the treatment of breast cancer

04/2021 MUDr. Tomáš Svoboda, Ph.D.; Bc. Daniela Čechová
Radiotherapy is one of the most basic methods of anticancer treatment, including breast cancer. It is used in a number of situations in terms of use, it is most often a standard part of adjuvant treatment, but it can be used at any time with a palliative intention, both in the area of primary tumor and metastatic disease in virtually any location. The method is undergoing huge development. Thanks to the use of modern diagnostic methods, planning has been significantly refined, fractionation regimes are undergoing development, and with much better instrumentation, much stricter limits can be applied to protect the surrounding organs. Radiation oncologists are able to respond to a wide range of situations, such as reconstructive procedures, adjustments of target volumes based on a comparison of risks against benefits, but also to replace previously common radical surgical procedures. Breast saving surgery and removal of only the sentinel node, in most cases supplemented by radiation therapy, represent a completely comparable alternative while maintaining the mental state, body integrity and quality of life of patients. On the contrary, studies based on the administration of systemic therapy in combination with radiotherapy with the omission of surgical treatment are currently underway. The results will certainly be interesting, but a relatively long follow up time will be needed to sufficiently compare the different approaches.

PI3K/Akt/mTOR signaling pathway and breast cancer – from molecular targets to clinical aspects

04/2021 Doc. MUDr. Jana Dvořáčková, Ph.D., MIAC; Mgr. Barbora Kubová; Mgr. Jarmila Šimová; RNDr. Magdalena Uvírová, Ph.D.
Breast cancer is one of the most common malignancies in women. The PI3K/Akt/mTOR signaling pathway plays an important role in several cellular processes involved in proliferation, metabolism, cell growth, and survival. Alterations in this signaling pathway have been found in a variety of tumors, including breast cancer. Constitutive activation of the PI3K/Akt/mTOR signaling pathway plays a key role in tumor pathogenesis and resistance to conventional therapy. In connection with the newly approved treatment with PI3K inhibitors, the determination of PIK3CA mutation status as a predictive marker is also gaining in importance.


04/2021 MUDr. Aleš Langer; MUDr. Hana Študentová, Ph.D.
Niraparib is younger member of PARP inhibitors family. Some PARP inhibitors are used in treatment of ovarian carcinoma routinely. This carcinoma is the most lethal of all Gynecological carcinomas. Incidence of this cancer is slightly decreasing, but it is still one of the most common cancers leading to death in women worldwide. The ovarian carcinomas are often diagnosed in an advanced clinical stage 3 or 4. Ovarian cancer is usually sensitive to platinum and taxane based chemotherapy, but treatment resistance and relapses develop throughout the disease course. Niraparib works as a maintenance therapy in a recurrent ovarian carcinoma. Niraparib provides the best results in BRCA1/2 mutated patients.

Molecular classification of endometrial cancers

04/2021 Doc. MUDr. Jiří Presl, Ph.D.; RNDr. Tomáš Vaněček, Ph.D.; prof. MUDr. Michal Michal; prof. MUDr. Jiří Bouda, Ph.D.; MUDr. Jan Kosťun, Ph.D.; MUDr. Pavel Vlasák; MUDr. Petr Straník
The basis for the diagnosis of endometrial carcinoma is histopathological morphology. Since 1983 we used Bokhman classic division of endometrial cancer on two relatively wide groups of tumors different in pathogenesis. This classification meets the didactic purpose, provides easy orientation for epidemiological data, but is not suitable for patient stratification. This division is carried out wide overlap of clinical, pathological and molecular tumor features. The Cancer Genome Atlas (TCGA) project classifies endometrial tumors into four groups based on molecular genetic features. Integration of the histopathological findings along with molecular classification appears to be the best approach for evaluating each individual tumor.

Cervical cancer screening and the role of HPV

04/2021 Doc. MUDr. Tomáš Fait, Ph.D
Human papillomaviruses (HPV) are the most important causative factor in the development of cervical cancer, but also other malignant and benign lesions of the female and male genitalia and partly other areas of the transition of the squamous and cylindrical epithelium. Preventing the acquisition of this infection is, in turn, the primary prevention of all of these lesions. The basis of secondary prevention, which is currently created only for the most common of the lesions cervical cancer is the early detection of cellular changes or detection of HPV infection, or a combination of both.

The role of brachytherapy in the treatment of locally advanced cervical cancer

04/2021 MUDr. Radovan Vojtíšek, Ph.D.
Brachytherapy is indicated for the treatment of all locally advanced cervical cancers. Conventional planning based on two orthogonal X rays does not take into account the response to external beam radiotherapy (EBRT) and is thus not consistent with the current individual tumor extent. The concept, which takes into account the change in tumor size and the topography of organs at risk at the end of initial EBRT, is image guided adaptive brachytherapy (IGABT). It also allows the dose from brachytherapy to be increased to the newly defined target volumes according to the risk of recurrence. Image guided adaptive brachytherapy has a positive effect on locoregional control and on the reduction of late postradiation toxicity. The gold standard in IGABT planning of cervical tumors is the use of magnetic resonance imaging. Current treatment recommendations are based on repeated evaluation of the tumor by clinical examination and imaging methods, optimally by magnetic resonance imaging, with subsequent adaptation of dose prescription and target volumes according to response and risk of recurrence.

Long‑term effect of panitumumab therapy in a patient with primarily generalized colorectal cancer – case report

04/2021 MUDr. Anna Nohejlová Medková
Colorectal cancer is one of the most common tumors in the Czech Republic. For metastatic patients with the wild type RAS gene, the therapy with monoclonal antibodies targeting epidermal growth factor receptor (EGFR) is available. Most patients develop skin toxicity with this therapy, which has a major impact on their quality of life; so prevention of side effects and testing of RAS genes leads to an improved management of patients with metastatic colorectal cancer. I describe a case of a patient who underwent the therapy with panitumumab and his multiple liver metastases have disappeared.