Despite the unprecedented success in using immune checkpoint inhibitors in the treatment of lung cancer, melanoma, hypermutable tumors of various localization, etc., a significant proportion of patients receiving these drugs do not respond to treatment. Predictive markers routinely used in the selection of patients for immunotherapy, in particular, the level of expression of PD -L1 and the presence of microsatellite instability, have certain limitations. Over the past decade, many other biomarkers designed to predict response to immunotherapy have been proposed, namely: tymor mutation burden, composition of lymphocytic infiltrate; allelic composition of the major histocompatibility complex; relationship between the numbers of different formed elements of blood as well as between its biochemical parameters; microflora of the digestive tract, etc. These markers can directly or indirectly reflect the immunogenicity of the tumor itself, as well as the state of systemic and intratumoral immune response. The predictive power and reliability of these markers are extremely different. When preparing this review, we conducted a literature search for recent studies regarding predictors of efficacy for immune checkpoint inhibitors published in the journals included in the databases, such as Pubmed, Web of Science, and Scopus.

Because of the high risk of brain metastases from HER2-positive breast cancer, the study of the anticancer activity of drugs used to treat brain tumors, in particular lomustine, is of great importance. In the FVB/N Her-2 transgenic mice bearing HER2-positive breast cancer (BC HER2+), a single oral administration of lomustine at a dose of 50 mg/kg resulted in a significant tumor growth inhibition (up to 96 %, p<0.0001). The tumor growth index (TGI) expressed as a ratio between the areas under the kinetic curves of tumor growth in the study and control groups and amounted to 33 % (p<0.001) indicated the high activity of lomustine. However, the effect of lomustine on intramuscularly transplanted Ehrlich tumor was insignificant (tumor growth inhibition and tumor growth index were <39 % and 68 %, respectively). Lomustine administered orally at a single dose of 50 mg/kg 24 hours after intracranial transplantation of BC HER2+ increased the median survival time up to 30 days in FVB/N mice compared to 21 days in the control group mice (p<0.001). The high therapeutic effect of lomustine in HER2-positive breast cancer mice is likely can be explained by the biological characteristics of this tumor; therefore clinical trials of lomustine for HER2-positive tumors are needed.

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Breast cancer (BC) is not a typical manifestation of Lynch syndrome. The existence and extent of excessive breast cancer risk in carriers of pathogenic mutations in the Lynch syndrome-associated genes (MLH1, MSH2, MSH6, PMS2) remains an open question. In addition, it is known that some of the breast neoplasms in patients with this syndrome are causally linked to the hereditary mutation, and some arise completely independently of the hereditary defect in the gene of the DNA mismatch repair system. In the case of accidental detection of such germline mutations in breast cancer patients, a thorough differential diagnosis between these categories of tumors is required, and the result of it is actionable, requiring changes in the management. This is a report of a case of breast cancer that arose in a carrier of a pathogenic mutation in the PMS2 gene, which was an accidental finding. The description of molecular genetic diagnostics is given: the microsatellite markers assessment and the detection of «loss of heterozygosity» allowed to classify the neoplasm in a category of cases that developed without any causal link to the patient's Lynch syndrome.