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The narrative review addresses the evidence that physical activity can improve the results of prevention and treatment and of the conditions that feature increased risks of their development with aging. The main attention is paid to cancer and problems arising because of physical activity limitations associated with COVID-19 pandemic. To promote physical activity, which is known to reduce the risks of COVID-19 complications and of cancer, it is important to help patients and physicians in understanding the reasons why physical activity can be beneficial, more than the pharmacological means thought to reproduce some of its effects, in cancer prevention and treatment upon all differences between the locations of tumors and the pathways of carcinogenesis. Therefore, the physiological and molecular mechanisms behind the usefulness of physical activity in oncology are discussed. Based on this discussion, data on quantitative relationships between oncological risks, physical activity, and the use of its alleged pharmacological mimetics are addressed. © 2021 Izdatel'stvo Meditsina. All rights reserved.

The review presents the data on the specifics of mechanism of action, classification, and clinical manifestations of neurotoxicity effect. The most significant features of specific side effects when using taxanes in different treatment regimens, including cumulative doses, are considered. The proven methods of treatment and prevention of neuropathy caused by anticancer drugs are discussed.

Relevance: early breast cancer is detected in more than 60% of cases. Maintaining the quality of life of patients with early breast cancer at the highest possible level is a priority, along with the treatment of patients. Under a complex antitumor treatment as well as after its completion, more than 60% of patients with early breast cancer report the occurrence of functional disorders.An important aspect is to improve the effectiveness of the rehabilitation process of patients with early breast cancer taking into account scientifically-based and proven recommendations.Objective: to evaluate the event-free survival rate (EFS) of patients with EBC undergoing rehabilitation within a biopsychosocial approach.Materials and methods: 228 patients with breast cancer who received complex treatment from 2015 to 2019 were included in the study. The prospective part of the study included 114 patients with early breast cancer undergoing rehabilitation measures within the biopsychosocial approach. The control group which was selected retrospectively, using the method of "pairwise selection", included 114 patients with early breast cancer comparable in age, stage of the disease, volume of surgical treatment and menopausal status, undergoing physical and psychological rehabilitation prescribed by a doctor. Patients in both groups were stratified depending on preoperative chemotherapy. EFS was calculated over a 2-year follow-up period. Events that were censored were a disease progression, the appearance of metastases, the occurrence of another cancer, a new concomitant disease, an exacerbation of the concomitant pathology and death.Results: Rehabilitation measures within the biopsychosocial model improve the indicators of EFS in the group of patients with EBC: EFS was 18.3 months against 14.5 months in the control group (HR=0.91, 95% CI [0.83; 0.99]; p=0.0034). In a multi-factor analysis the key factors affecting EFS were neoadjuvant chemotherapy (HR=0.79, 95% CI [0.69; 0.94]; p=0.0025), age (HR=0.87, 95% CI [0.71;1.09]; p=0.0027) and menopausal status (HR=0.85, 95% CI [0.84; 0.95]; p=0.0022) (table 1). Conclusions: Rehabilitation measures within the biopsychosocial model improve the indicators of EFS in the group of patients with early breast cancer, the key factors affecting EFS were neoadjuvant chemotherapy, age and menopausal status. Table 1 Multi-factor analysis of event-free survival of patients with early breast cancer in the group of biopsychosocial model of rehabilitation versus control group.CharacteristicNumber of patientsHR (95% CI)Preoperative chemotherapyyes1520,84 (0,77; 1,1)no760,79 (0,69; 0,94)Menopauseyes1300,84 (0,77; 1,04)no980,85 (0,84; 0,95)Age group25-44610,87 (0,71; 1,09)45-601030,89 (0,74; 1,1)61-75641,01 (0,82; 1,24)EventDisease progression281,11 (0,86; 1,26)Exacerbation of the concomitant pathology160,83 (0,74; 0,96) Citation Format: Valeria Kluge, Tatiana Semiglazova, Petr Krivorotko, Elena Melnikova, Vladislav Semiglazov, Kristina Kondrateva, Svetlana Nazarova, Margarita Tynkasova, Bahtiyar Adhamov, Roman Pesotsky, Konstantin Zernov, Valentina Chulkova, Boris Kasparov, Denis Kovlen, Vladimir Semiglazov, Alexey Belyaev. Biopsychosocial approach in the rehabilitation of patients with early breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-62.

Background Previous studies on neoadjuvant therapy for BRCA1-driven ovarian cancer (OC) demonstrated higher efficacy of mitomycin C plus cisplatin combination as compared to standard drug schemes. These data call for evaluation of the utility of this regimen for the treatment of recurrent BRCA1-associated OC. Methods The study included 12 BRCA1 germ-line mutation carriers, whose disease relapsed after one (n = 4) or two (n = 8) lines of chemotherapy. The patients received cisplatin 100 mg/m2 and mitomycin C 10 mg/m2, given every four weeks, for 6 (n = 10), 8 (n = 1) or 5 (n = 1) cycles. Retrospective data on conventional treatment of OC relapses in BRCA1 heterozygotes (n = 47) served as a control. Results Grade 3–4 toxicities were observed in 4/12 (33%) cases. There were 6 complete responses (CR), 4 partial responses (PR) and 2 instances of stable disease (SD). Comparison of patients receiving mitomycin C plus cisplatin (n = 4) or conventional therapy (n = 44) at first relapse demonstrated marginal improvement of the progression-free survival (PFS) (16.6 months vs. 10.2 months, P = .067). Use of mitomycin C plus cisplatin (n = 8) for the treatment of second relapse resulted in significant prolongation of PFS as compared to standard regimens (n = 31) (14.8 months vs. 4.8 months, P = .002). Conclusions Mitomycin C plus cisplatin shows promising activity in recurrent BRCA1-driven ovarian cancer.

Introduction: The effects of chemotherapy are known to depend on the time of administration. Circadian rhythms are disturbed in tumors and in tumor bearers. Agents involved in controlling the circadian rhythms (chronobiotics) potentially can modify the outcomes of chemotherapeutics administered at different times of the day. Pineal hormone melatonin (MT) is a prototypic chronobiotic. Objective: The aim of the study was to investigate if MT can affect efficacy or toxicity of chemotherapy drugs administered at the extreme time points of the working day of hospital personnel. Methods: Cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) and adriamycin and docetaxel (AT) cytotoxic drug combinations were administered on day 0 at 11:00 a.m. or at 5:00 p.m. (UTC+03:00) to 6-month-old female HER2/neu transgenic FVB/N mice bearing mammary adenocarcinomas. Some mice were additionally provided with MT in drinking water (20 mg/L) at night 1 week before or 3 weeks after treatment or during both periods. Tumor node sizes, body weight, and blood cell counts were determined right before treatment and on days 2, 7, 14, and 21. Results: Significant decrease in the mean tumor node volume was found by days 14 and 21 upon all CAF and AT treatment schedules, except in animals treated with AT at 5:00 p.m. without supplementation with MT. In the latter case, mean tumor node volume on day 21 was the same as in the control. Supplementation of AT administered at 5:00 p.m. with MT improved the tumor response. CAF and AT regimens supplemented with MT also augmented the number of tumor nodes that did not increase by more than 20% by day 21 as compared to CAF or AT alone, respectively. This effect was significant in groups treated with AT at 5:00 p.m. and consistent upon other schedules. On day 7, leukopenia and anemia were registered in groups treated with CAF regimen; however, blood cell counts normalized by day 14. Both CAF and AT were associated with drop in the body weight registered on day 7. Supplementation with MT did not affect changes of the body weight and blood counts. Conclusions: MT supplementation to cytotoxic drugs can improve antitumor response, especially if it is blunted because of an inappropriate time of administration.

Relevance: The strategy of finding evidence on the use of rehabilitation technologies in patients with lung cancer is based on scientometric analysis. Methods: For the period from 1991 to 2018. Using PICO (T) technology in electronic databases (PEDro, PubMed, Elibrary, Cochrane Library), full-text analysis of 249682 studies was performed. MeSH bibliographic descriptors: «lung cancer», «rehabilitation», «physical therapy». Studies were evaluated on a PEDro scale, which includes 10 parameters of the level of evidence: randomization, endpoint evaluation, blinding, etc. Results: The verified distribution profile of research on the quality of evidence showed that 55.9% of studies had a quality level of 4 to 8 on the PEDro scale. One study had a quality level of 9 points (0.8%). The bulk of research (69%) is devoted to the study of the effectiveness of exercise. Evaluation of the effectiveness of respiratory gymnastics, traditional health practices (Tai Chi, gypsy, yoga, etc.) are devoted to 7.5% of the studies. 6.5% of works are devoted to studying the effectiveness of acupuncture. Analysis of the effectiveness of non-invasive ventilation technology (mainly CPAP), the effects of artificially modified air (aerosol therapy, aerophytotherapy), and therapeutic physical factors of mechanical nature (massage, vibrotherapy) is devoted to 10.8% of studies. The use of technologies of physical rehabilitation measures using electromagnetic factors is devoted to 3.2%. In 2% of the studies, an assessment of the effectiveness of respiratory gymnastics was presented, and in a number of works, such technologies of physical rehabilitation, which are gaining popularity in the rehabilitation of patients with lung cancer, have been studied as kinesio-taping and audio-visual relaxation (1% each). Conclusion: Clinical recommendations developed on the basis of the obtained results will form the basis of a new, evidence-based stage in the development of the rehabilitation of patients with lung cancer in Russia.

PALB2 is а high-penetrance gene for hereditary breast cancer (BC). Our study aimed to investigate the spectrum of PALB2 mutations in Russian cancer patients. PALB2 sequencing revealed pathogenic variants in 3/190 (1.6%) young-onset and/or familial and/or bilateral BC cases but none in 96 ovarian cancer (OC) or 172 pancreatic cancer patients. Subsequently, seven recurrent PALB2 pathogenic alleles were selected from this and previous Slavic studies and tested in an extended patient series. PALB2 pathogenic variants were detected in 5/585 (0.9%) "high-risk" BC, 10/1508 (0.7%) consecutive BC and 5/1802 (0.3%) OC cases. Haplotyping suggested that subjects with Slavic alleles c.509-510delGA (n = 10) and c.172-175delTTGT (n = 4) as well as carriers of Finnish c.1592delT mutation (n = 4) originated from a single founder each, while PALB2 p.R414X allele (n = 4) had at least two independent founders. Somatic loss of heterozygosity (LOH) was revealed in 5/10 chemonaive BCs and in 0/2 BC samples obtained after neoadjuvant therapy. Multigene sequencing identified somatic PALB2 inactivating point mutation in one out of two tumors without PALB2 LOH but in none of four BCs with PALB2 LOH. Genomic instability, as determined by NGS, was observed in four out of five tumors with biallelic PALB2 inactivation but not in the BC sample with the preserved wild-type PALB2 allele. PALB2 germ-line mutations contribute to a small fraction of cancer cases in Russia. The majority although not all PALB2-driven BCs have somatic inactivation of the remaining PALB2 allele and therefore potential sensitivity to platinum compounds and PARP inhibitors.

The spectrum of BRCA1 and BRCA2 mutations in Slavic countries is characterized by a high prevalence of founder alleles. We analyzed a large data set of Russian breast cancer (BC) and ovarian cancer (OC) patients, who were subjected to founder mutation tests or full-length BRCA1 and BRCA2 analysis. The most commonly applied test, which included four founder mutations (BRCA1: 5382insC, 4153delA, 185delAG; BRCA2: 6174delT), identified BRCA1 or BRCA2 heterozygosity in 399/8533 (4.7%) consecutive BC patients, 230/2317 (9.9%) OC patients, and 30/118 (25.4%) women with a combination of BC and OC. The addition of another four recurrent BRCA1 mutations to the test (BRCA1 C61G, 2080delA, 3819del5, 3875del4) resulted in evident increase in the number of identified mutation carriers (BC: 16/993 (1.6%); OC: 34/1289 (2.6%); BC + OC: 2/39 (5.1%)). Full-length sequencing of the entire BRCA1 and BRCA2 coding region was applied to 785 women, very most of whom demonstrated clinical signs of BRCA-driven disease, but turned out negative for all described above founder alleles. This analysis revealed additional BRCA1 or BRCA2 mutation carriers in 54/282 (19.1%) BC, 50/472 (10.6%) OC, and 13/31 (42%) BC + OC patients. The analysis of frequencies of founder and “rare” BRCA1 and BRCA2 pathogenic alleles across various clinical subgroups (BC vs. OC vs. BC + OC; family history positive vs. negative; young vs. late-onset; none vs. single vs. multiple clinical indicators of BRCA1- or BRCA2-associated disease) revealed that comprehensive BRCA1 and BRCA2 analysis increased more than twice the number of identified mutation carriers in all categories of the examined women. Full-length BRCA1 and BRCA2 sequencing is strongly advised to Slavic subjects, who have medical indications for BRCA1 and BRCA2 testing but are negative for recurrent BRCA1 and BRCA2 mutations.

ObjectivesCisplatin and mitomycin C exert high activity towards BRCA1-deficient cells. This study aimed to evaluate the efficacy of a combination of these drugs in hereditary BRCA1-associated ovarian cancer (OC).MethodsTwelve OC patients, who could not be treated by primary debulking surgery owing to extensive tumor spread, were given neoadjuvant cisplatin (100 mg/m2) and mitomycin C (10 mg/m2) every 4 weeks for 3 (n = 9), 2 (n = 2), or 4 (n = 1) cycles.ResultsThe decrease of tumor burden and complete surgical cytoreduction were achieved in all patients. Pathologic complete response, defined as the absence of tumor cells in surgically removed tissues, was observed in 2 (17%) of 12 cases. Retrospective analysis of 62 OC in BRCA1 mutation carriers subjected to conventional neoadjuvant chemotherapy schemes revealed 36 objective tumor responses (58%) and 37 instances (60%) of complete cytoreductive surgery; however, none of these patients demonstrated pathologic complete response.ConclusionsThe combination of cisplatin plus mitomycin C showed promising results in BRCA1-driven OC and therefore deserves further clinical evaluation.

The conference "Results and prospects of development of new polyphenolic drugs for cancer patients" took place at the N.N. Petrov National Medical Research Center of Oncology (PNMRCO) on May 31, 2017, and gathered researchers involved in development and evaluation of medicinal products based on the novel lignin-derived soluble polyphenolic polymer BP-Cx-1. BP-Cx-1 is the platform for a portfolio of innovative pharmacological products such as BP-C1, BP-C2 and BP-C3.

Large genomic rearrangements (LGRs) constitute a significant share of pathogenic BRCA1 mutations. Multiplex ligation-dependent probe amplification (MLPA) is a leading method for LGR detection; however, it is entirely based on the use of commercial kits, includes relatively time-consuming hybridization step, and is not convenient for large-scale screening of recurrent LGRs. We developed and validated the droplet digital PCR (ddPCR) assay, which covers the entire coding region of BRCA1 gene and is capable to precisely quantitate the copy number for each exon. 141 breast cancer (BC) patients, who demonstrated evident clinical features of hereditary BC but turned out to be negative for founder BRCA1/2 mutations, were subjected to the LGR analysis. Four patients with LGR were identified, with three cases of exon 8 deletion and one women carrying the deletion of exons 5–7. Excellent concordance with MLPA test was observed. Exon 8 copy number was tested in additional 720 BC and 184 ovarian cancer (OC) high-risk patients, and another four cases with the deletion were revealed; MLPA re-analysis demonstrated that exon 8 loss was a part of a larger genetic alteration in two cases, while the remaining two patients had isolated defect of exon 8. Long-range PCR and next generation sequencing of DNA samples carrying exon 8 deletion revealed two types of recurrent LGRs. Droplet digital PCR is a reliable tool for the detection of large genomic rearrangements.