Libor Staněk, Petra Tesařová
Dagmar Brančíková, Markéta Protivánková
Anna Rubešová, Michaela Čadková Svejkovská, Zita Dubová
New recommendations for testing of hereditary breast and ovarian carcinomas in routine clinical practice
The breast carcinoma belongs to the most frequently occurred malignant tumours by females. 90 up to 95 % of tumours emerge coincidentally. 5 up to 10% of tumours belong to hereditary tumours. The most common cause of the hereditary tumours is the mutation of the gene BRCA1/2. The following article deals with indication for the genetic test and medical care about those affected female patients.
Triple negative breast carcinoma accounts for approximately 15-20 % of all breast carcinoma and is characterized by loss of expression of a-estrogen, progesterone and HER2 receptors, predominantly low differentiation, mostly in the basal form of the subgroup. They are more common in younger women and are associated with the occurrence of hereditary or sporadic forms of breast cancer caused by a pathogenic mutation in the BRCA1 and BRCA2 gene or another genetic disorder leading to HR-deficient tumors.
Hereditary cause, inherited mutation in BRCA1 or BRCA2 genes, is responsible for 3-5% of unselected breast cancer cases and 15-20% of ovarian cancer cases. The carriers of these mutations have many times increased risk of breast, ovarian cancer, but also the risks of other solid tumors. Preventive care should be offered through comprehensive oncology and gynecology centers. Women carriers of mutations should be seen from age of 25 by oncologist every 6 month with ultrasound and MRI of breasts, from 30-65 with mammography and MRI, followed by ultrasound and mammography itself. Prophylactic bilateral mastectomy decreases the risk of breast cancer from 85% of lifetime risk to only 1-5%. Prophylactic oophorectomy is necessary for the reduction of risk of ovarian cancer, since no preventive care is effective for early detection of ovarian cancer. Explaining all these preventive procedures, their importance for cancer risk reduction, is important part of specialized preventive care.
A new drug using a unique mechanism of action - an intervention in DNA repair - is being introduced into the treatment of ovarian cancer. Olaparib is a drug of the so-called PARP inhibitor group. Interference with the mechanism of DNA repair is particularly effective in BRCA1/2 gene mutation carriers, in whom one of reparation ways is primarily faulty by a germ-line or somatic mutation. Olaparib in the treatment of platinum-sensitive recurrent ovarian cancer in BRCA1/2 mutation carries leads to prolonged progression-free survival and increased overall survival.
Treatment of locally advanced breast cancer with HER2/neu amplification is systemic and consists of chemotherapy and receptor blockade. The neoadjuvant procedure is designed to rapidly reduce tumor mass and operability, despite the misgivings of several studies, the complete remission remains pathological (pCR) is a reliable substitute Time to progression or overall survival. In this paper we present a summary of some experience with chemotherapy regimens and HER2/neu blockers and their potential combinations. The most promising 3-year data from trial NeoSphere show a promising trend to improve progression free survival for the combination of docetaxel/trastuzumab/pertuzumab that increased pCR from 29% to 46%. In all neoadjuvant studies, the group of patients with a hormone-positive disease had less benefit from anti-HER2 blockade and chemotherapy, but this procedure has yet to be verified as the best.
Hormonal treatment in patients with disseminated, hormonal dependent breast cancer is a clearly preferred treatment alternative. It should be considered in all patients, regardless of the extent and location of the disease. Only in the case of a rapidly progressive and aggressive disease with signs of a visceral crisis is chemotherapy an option, because the onset of chemotherapy is faster than the onset of the hormone treatment. Currently, the possibilities of hormonal therapy of advanced breast cancer are changing - due to the combination of hormone therapy with cyclin-dependent kinase 4/6 inhibitors (CDK4/6), there has been a marked improvement in the effectiveness of therapy. Improvement in treatment occurred in all subgroups of patients who received CDK4/6 inhibitors. Until now, no predictor has been identified. Palbociclib, ribociclib, and abemaciclib were evaluated in clinical trials. This article summarizes the effectiveness and tolerance of these preparations.
Winning smile of Monaleesa – ribociclib in the first line of palliative treatment of hormone dependent breast cancer
A new group of targeted drugs is coming to the fore of clinical practice in endocrine dependent metastatic breast cancer. At this point CDK4/6 inhibitors are introduced whereas given in combination with aromatase inhibitors. The most recently published data from MONALLESA-2 study with letrozol and ribociclib show very high efectivity and good toxicity profile of this combination. The median PFS in ribociclib arm was not reached in this study until now. It seems to us that this regimen has a big chance to become a new treatment standard in the first line setting soon as it is proved already in the most important treatment guidelines worldwide.
Breast cancer is highly heterogeneous and its different types are differently susceptible to therapy. Some types are hard to manage and some are practically incurable. It is therefore important to find new target sites that would not be subject to mutations and that would be utilised for targeted therapy of neoplastic diseases with limited toxicity of normal tissues. Therefore, we designed and tested a novel anti-cancer agent derived from tamoxifen, which is targeted to mitochondria. Contrary to tamoxifen, the new agent is efficient against hard-to-treat types of breast cancer. We are currently preparing phase 1 clinical trial of our new agent.
An immuno-therapy directed at the inhibition of PD-L1 (programmed death-ligand 1) protein ligand in patients with non-small cell lung cancer in the second or third line of treatment is reported, according to the results of the POPLAR and OAK studies. The atezolizumab treatment product showed an improvement in survival compared to docetaxel in all subgroups of patients with the exception of tumors with epidermal growth factor receptor and anaplastic lymphoma kinase positivity. Efficacy was greatest in tumors with high expression of PD-L1 and large lymphocytic infiltration of the tumor but was found even in low or inconclusive expression. The drug was very well tolerated and is another hope for patients with metastatic and locally advanced non-small cell lung carcinoma.
Optimal procedures in systemic treatment of gastrointestinal stromal tumors: current procedures, novelties, treatment perspectives
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of gastrointestinal tract. Oncogenic activating mutations in the receptor tyrosine kinases KIT (78 %) and PDGFRA (platelet-derived growth factor receptor alpha; 5-8 %) play a crucial role in the molecular pathogenesis of GIST. Better treatment strategies and targeted therapies have improved survival rates for patients with GIST significantly. Imatinib, the receptor tyrosine kinase inhibitor, has revolutionized the therapeutic landscape for GIST patients and remains the mainstay first-line clinical option for both unresectable and advanced GISTs, as well as for adjuvant treatment after resection of high risk GIST. Sunitinib is indicated as second-line therapy. Regorafenib has been approved as third-line treatment of patients who progressed on or are intolerant to prior imatinib and sunitinib. Early identification of patients with suboptimal response to therapy is an important issue of a personalized treatment of patients with GIST.
Pancreatic cancer is a highly aggressive malignancy with poor treatment results at all stages. At the time of diagnosis, metastatic spread or locally advanced disease is present in most patients. Despite low efficacy, gemcitabine monotherapy has been used in palliative treatment of advanced disease for many years. In recent years therapeutic options have expanded significantly. In palliative treatment of the first line, FOLFIRINOX and nab-paclitaxel/ gemcitabine regimens have been introduced into clinical routine, which increased the overall survival by 4-5 months. Other possibilities prolongation of survival is the second line treatment with nanoliposomal irinotecan in combination with 5-fluorouracil and leucovorin in patients pretreated with gemcitabine regimen. Interesting results brings the studies aimed at influencing the extracellular matrix of tumor cells.
The activating epidermal growth factor receptor mutation is present in almost 50% of patients with advanced non-small cell lung cancer, who are of Asian ethnicity1 compared with only 12% in the Caucasian population.2 These molecular alterations predict sensitivity to first and second generation epidermal growth factor receptor tyrosine kinase inhibitors such as erlotinib, gefitinib, afatinib. Response rate and progression-free survival with epidermal growth factor receptor tyrosine kinase inhibitors are superior to standard first-line platinum doublet chemotherapy, making them the standard of care.
Psychosocial care provided to people with cancer improves quality of their lives and reduces treatment costs. A survey, the first of its kind in the Czech Republic, was conducted to identify the needs of these patients and the importance of their needs. In order to explore the needs we have created a questionnaire, which was completed by 253 respondents. Responses showed that patients with cancer have a special need for a good relationship with health care professionals, psychological support and information regarding what state support they are entitled to during and after the disease. In all these areas, care of cancer patients can be improved.