Background. By 2020, breast cancer (BC) has become the most frequent malignancy in the world. The most common type of BC is HR+/HER2-negative cancer,2540% of which harbors PIK3CA mutations that affect the catalytic subunit of the PI3K protein. PIK3CA alterations are actionable, as such neoplasms can be treated with a combination of fulvestrant and the PI3K inhibitor alpelisib. As PIK3CA mutations have an extremely versatile effect on the characteristics of a tumor cell, numerous associations of PIK3CA mutations and various clinico-pathological characteristics of BC can be traced. Aim. Our aim was to clarify the information on the frequency and spectrum of PIK3CA mutations in Russian patients with HR+/HER2- advanced BC, and to study the association of PIK3CA mutations with clinical and pathological parameters of BC. Materials and methods. Tissue samples from 694 patients with HR+/HER2- advanced BC (mixed population of primary metastatic and relapsed tumors) who received any line of anti-cancer treatment in Dec 2020 to June 2021 in Russian Federation were analyzed by high-resolution melting, allele-specific PCR, digital droplet PCR and Sanger sequencing (exons 7,9, and 20 of the PIK3CA gene). Mutation rates in different BC subgroups were compared using the Fishers exact test. The age at diagnosis in patients with different PIK3CA status was compared using the MannWhitney U-test. The relationship between the PIK3CA status and the degree of tumor differentiation was compared using the CochraneArmitage test for trends. Luminal A and B BC expression subtypes were distinguished with surrogate IHC markers according to St.-Gallen recommendations (2013). Results. Mutations were identified in 220/694 (32%) BC patients. The three most frequent missense substitutions in the PIK3CA gene (p.E542K, p.E545K, and p.H1047R) accounted for 190/220 (86%) mutations. Associations of PIK3CA mutations with luminal A subtype of BC, low proliferation index, small size of the primary tumor, and absence of signs of hereditary cancer were revealed. Associations of mutations in the kinase domain of PIK3CA (p.H1047R) with late recurrence of locally advanced BC and with non-Slavic ethnic origin of patients were found. Conclusion. PIK3CA mutation rate of 32% confirms high prevalence of mutation in Russian population, with some differences reflecting the ethnic origin of patients.
An obvious trend of the last decade in head and neck squamous cell carcinoma pathogenesis evaluation is awareness of the impact of immune response disorders on disease manifestation. The review presents an analysis of the differences in the type and degree of immunosuppression, as well as treatment response in head and neck squamous cell carcinoma patients in accordance with influencing carcinogenic factor, gender, age of the patient and concomitant diseases. An increase in CD8+ T-lymphocytes and a decrease of memory T-cells has been evaluated in smoking and alcohol abusing patients with head and neck squamous cell carcinoma, and a smaller number of CD8+ T-lymphocytes were detected in the tumor microenvironment compared to non-smoking and non-drinking patients. Studies have shown that the improved prognosis of patients with human papillomavirus (Hpv) – associated head and neck squamous cell carcinoma is largely due to the presence of antibodies against Hpv E6 and E7, E7-specific CD8+T lymphocytes in periphe ral blood and a high level of tumor-infiltrating T lymphocytes. The issue of gender differences in the type of immune response is widely discussed. It has been shown that the use of immune response checkpoint inhibitors is more effective in improving survival rates in men, and the use of these drugs in combination with chemotherapy is more effective in women. In addition, in elderly cancer patients, numerous age-associated T-lymphocyte’s function changes were revealed, including a decrease in the number of naive T-lymphocytes due to age-related involution of the thymus and an in crease in the relative number of memory cells and effector cells. Thus, it is clear that immunosuppression type, as well as treatment response, differ depending on the influencing factor, gender, age of the patient, as well as comorbidities.
Deficient DNA mismatch repair (dMMR) is a rare molecular disorder found in 20-30 % of endometrial tumors. Laboratory identification of dMMR/microsatellite instability (MSI) has a high diagnostic value, since these impairments are considered as biomarkers of endometrial adenocarcinoma. They help to identify patients at high risk of Lynch syndrome, evaluate the disease prognosis, and estimate the efficacy of immune checkpoint inhibitors and their combinations. This review details current concepts of MSI diagnostics and discusses its predictive value in patients with endometrial cancer. It also describes a new diagnostic algorithm for the detection of dMMR and MSI.
Hepatocellular carcinoma (HCC) is a public health problem worldwide and is one of the most common and lethal cancers worldwide, the sixth among the most common cancers and the second mortal cancer worldwide. Viral hepatitis is the main risk factor. Growing evidence suggests that the metabolic syndrome, which includes hyperlipidemia, dyslipidemia, and hypertension, increases the risk of developing HCC. Epidemic of obesity, the proportion of HCC with non-alcoholic fatty liver disease (NAFLD) in the Russian population is 17.4 %. In clinical practice, it is often difficult to identify the leading etiological factor. In a patient with concomitant viral hepatitis, HCC may be associated with alcohol abuse or metabolic disorders. In clinical trials, investigators evaluate the most likely etiology of HCC, and studies analyze subgroup: HBV, HCV, and non-viral etiologies, which include a variety of liver diseases: alcoholic liver disease, NAFLD, autoimmune hepatitis, and others. Differences in the effectiveness of systemic therapy depend on the main etiological factor has been published recently. Pivotal studies of combinations of immuno-oncological drugs have shown mixed results in efficacy. For the combination of atezolizumab with bevacizumab and pembrolizumab with lenvatinib, there was no difference in OS in non-viral subgroups, although the difference was significant for the combination of durvalumab with tremelimumab compared with TKIs from the control group. A multivariate analysis of patient characteristics showed that lenvatinib is an independent prognostic factor for OS, reducing the risk of death by 35 % compared with atezolizumab in combination with bevacizumab in patients with non-viral HCC etiology in the A. Casadei-Gardini study. The same has been proven for the NASH/NAFLD subgroup. Currently, it is difficult to conduct prospective clinical trials to assess the efficacy and safety of treatment depending on the etiology, it is important to focus on data from real-world evidence in order to have guidelines for making decisions regarding the treatment of non-viral HCC.
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