[Tumor infiltrating lymphocytes (TILs) in triple negative breast cancer]. / Infil'triruyushchie opukhol' limfotsity (TILs) pri trizhdy negativnom rake molochnoi zhelezy.

BACKGROUND: Tumor infiltrating lymphocytes (TILs) are a promising inexpensive prognostic and predictive biomarker in breast cancer. High levels of TILs are associated with improved survival and higher probability to achieve pathological complete response in triple-negative breast cancer (TNBC). OBJECTIVE: To assess the level of TILs in TNBC samples and analyze the association between the level of TILs and the main pathological parameters, to identify their impact on long-term results. MATERIAL AND METHODS: The study included information on 140 patients with I-III stage TNBC and estrogen receptors <10%. Tumor tissue samples at baseline biopsies were evaluated the histological type, HER2 expression, estrogen expression levels, Ki-67 and TILs. The pathological response was evaluated according to the ypTNM, Miller-Payne, and RCB classifications. RESULTS: The average level of TILs in biopsy specimens before NACT was 29.3±23.1%. Low levels of TILs (<10%) were defined in 21% of cases, intermediate levels (≥10% to ≤40%) in 55% of cases, and high levels (>40%) in 24% of cases. Using the two-tiered system, low TILs (≤40%) were defined in 76% and high TILs (>40%) in 24% of cases. The level of TILs was correlated with histological grade (R=0.187; p=0.027) and estrogen receptor expression level (R=0.211; p=0.012). There were no significant differences depending on the level of TILs and other pathological parameters. Three-year event-free survival (EFS) in patients with high TILs levels was 95% versus 65% in the low TILs group (p=0.037). CONCLUSION: Stromal TILs are an important prognostic biomarker in TNBC. Using a cutoff of 40%, high TILs are significantly associated with longer EFS.

[Comprehensive analysis of the efficacy of personalized rehabilitation programs in patients with breast cancer]. / Kompleksnyi analiz effektivnosti personalizirovannykh programm reabilitatsii bol'nykh rakom molochnoi zhelezy.

The concept of the personalized rehabilitation is based on the principle of applying physical and rehabilitative medicine techniques depending on the factors that mostly influence on rehabilitation efficacy in a particular patient - determinant of effectiveness. Current achievements in the diagnosis and treatment of breast cancer (BC) significantly increased overall patients' life expectancy, updating rehabilitative treatment stage, which is often unmet. OBJECTIVE: To perform the comprehensive analysis of the efficacy of personalized rehabilitation programs in patients with BC. MATERIAL AND METHODS: The combined comparative multi-centre randomised trial of rehabilitation program efficacy in patients with breast cancer was done. The study included 219 patients aged from 30 to 45 years (median 39.4 year), who were divided into 2 groups. The rehabilitation by programs, that included current personalized rehabilitative techniques (RT) with proved efficiency, based on scientometrical analysis of evidential research was performed in the first group patients. In the second group aftercare was done according to the standard programs. The comprehensive evaluation of treatment efficacy was conducted in several stages: 1) performance analysis of rehabilitative programs; 2) verification of the effectiveness' determinant of rehabilitation; 3) factor analysis to assess the mechanisms of therapeutic effects in experimental groups; 4) comparative analysis of alternative strategies for selecting rehabilitation programs. RESULTS: The use of rehabilitative programs, based on recommended RT, changes the rehabilitation structure, significantly increasing its efficacy by 17%. Furthermore, the percentage of high-efficiency usage of this type programs increases by 17% compared with standard programs. The main determinants, affecting the efficacy of rehabilitation programs, based on selected RT, are anamnestic data, parameters of exercise tolerance and physical activity and ultrasound parameters of upper limb blood flow. The therapeutic effects of personalized rehabilitation programs are realized by correction of clinical rates, increasing exercise tolerance and physical activity, as well as psychophysiological parameters. CONCLUSION: The use of the evaluation system of anamnestic, clinical, functional and psychophysiological features of patient (the effectiveness' determinant) in realization of personalized rehabilitation programs for women with BC, allows to predict and manage the efficacy of RT applying.

[The role of comprehensive geriatric assessment in the treatment of cancer patients in elderly and senile age.]

Modern approaches to the organization of diagnosis and treatment of elderly and senile patients with malignant tumors allow to maintain the necessary level of health, improve the quality of life and increase life expectancy. Assessment of geriatric status in Oncology allows: to predict complications during the complex treatment, including drug treatment; to modify treatment to reduce the risk factors of adverse outcomes; to select patients for specialized treatment using standard schemes. So, timely assessment of geriatric syndromes and their correction can expand the indications for specialized treatment of elderly and senile patients.

Diagnosis and treatment of phylloides tumors of the breast.

Phylloides tumors (PT) are a rare and the least studied pathology of the breast. Data on physical examination and imaging methods of diagnostics in most cases do not allow accurate diagnosing at the preoperative stage as there are no clear characteristics that allow differentiating benign from malignant variants of PT or other benign breast diseases. Surgery is the main treatment of PT. Chemotherapy and radiation therapy of malignant variants of PT in the adjuvant setting do not significantly improve survival rates. In recurrent or metastatic forms of PT these methods can be effective in some cases. Currently there are identified molecular signaling pathways that play an important role in the pathogenesis of PT. Thus there are prerequisites for the study of the effectiveness of targeted therapies for this pathology.

[Hyperthermic intraperitoneal chemotherapy combined with cytoreductive procedure in patients with peritoneal pseudomyxoma].

AIM: To study the results of intraperitoneal chemoperfusion combined with cytoreductive procedure in patients with peritoneal pseudomyxoma. MATERIAL AND METHODS: For the period 2006--2015 seven patients with peritoneal pseudomyxoma underwent aggressive treatment using hyperthermic intraperitoneal chemoperfusion combined with cytoreductive procedure at the Department of General Oncology of N.N. Petrov Research Institute of Oncology. RESULTS: Two patients had postoperative complications. One of them died after 12 days postoperatively. Features of postoperative complications were predominantly determined by volume of cytoreduction. Advanced tumoral process caused death in 2 patients additionally. Other patients are still alive during 4--28 months after surgery. CONCLUSION: Hyperthermic intraperitoneal chemoperfusion combined with cytoreductive procedure is advisable for peritoneal pseudomyxoma to improve survival. Optimal cytoreduction should be developed in researches with large number of patients to decrease incidence of complications.

[BREAST-CONSERVING SURGERY AFTER NEOADJUVANT THERAPY FOR BREAST CANCER].

In the randomized phase 2 study there was evaluated the efficacy of neoadjuvant endocrine treatment (anastrozole, exemestane) in comparison with chemotherapy (doxorubicin plus paclitaxel). Preoperative endocrine therapy was well tolerated. There was a trend towards higher overall rates of objective response and breast conserving surgery (BCS) among patients with tumors expressing high levels of ER (luminal A) in endocrine therapy group compared with chemotherapy group (43% vs 24%; p = 0,054). In HER2-positive breast cancer patients the addition of trastuzumab to neoadjuvant chemotherapy improved the overall and pathological complete response. Trastuzumab made possible an increasing number of breast conserving surgery (23% vs 13%; p = 0,022). No patient treated with trastuzumab and with chemotherapy had a local recurrence after BCS.

[Adjuvant chemotherapy for breast cancer: search for new ways of planning].

A decision regarding adjuvant chemotherapy in early (operable) breast cancer in the past was made entirely on the basis of clinical and pathological features. However with the growing awareness of tumor biology and the possibility of the genomic analysis to determine the molecular subtypes of breast cancer it is getting real to identify patients whose tumors are resistant to chemotherapy or vice versa benefit from its addition. Despite the fact that genomic analysis allows some patients avoiding chemotherapy (especially patients with localized breast cancer), such studies do not indicate the most appropriate chemotherapy regimens. Therefore treatment decisions should be based on a combination of biological features of the tumor, its stage and signs that characterize the patient such as age and tolerance to the side effects of therapy.

[The effectiveness of ultrasound and sonoelastography in the diagnosis of palpable and non-palpable breast lesions].

The purpose of this study was to analyze the causes of false results in the ultrasound (US) and sonoelastography (SEG) examination of non-palpable and palpable lesions of the breast. The efficacy of diagnosis of non-palpable and palpable lesions by US and SEG was compared. 211 women with histologically confirmed focal breast lesions (146 non-palpable and 65 palpable) were included in the group. Women had a mean age of 52.0 +/- 13.6 years. The diameter of non-palpable lesions was less than 2 cm. Local mastopathy and medullar carcinoma were the reason of false results in most US. SEG allowed differentiating of these lesions. We found that SEG increased the specificity of diagnostics of non-palpable breast lesions by 19%.

[Clinical and morphological features and treatment for lobular breast cancer].

The study presents data on the treatment of lobular breast cancer. On the basis of the studied morphological and molecular-biological characteristics there were substantiated types of treatment that improved the survival of patients with invasive lobular carcinoma. It was showed the efficacy of systemic treatment for lobular breast cancer and also studied long-term outcomes of lobular breast cancer depending on the morphological and biological features.

[HER2-positive breast cancer: standard and double targeted therapy].

Neoadjuvant systemic therapy is frequently used option for the systemic treatment for breast cancer. Inclusion in the regimen of targeted drugs as trastuzumab (Herceptin) and pertuzumab significantly improves outcomes in HER2-positive breast cancer patients. A certain part of HER2-positive patients can be cured by using only targeted drugs without chemotherapy.

[Markers of effectiveness of preoperative taxane-based chemotherapy for locally advanced breast cancer].

The absolute sensitivity signs of breast cancer to the drug have not yet been developed. Data from clinical trials on the study of experimental laboratory predictive markers of chemosensitivity: TOP2alpha (topoisomerase 2-alpha), beta-tubulin (subunit of dimeric protein tubulin), and BRCA1 (breast cancer 1) are contradictory and not numerous. Analysis of the results by the end of the clinical trial will allow examining the correlation between the effectiveness of preoperative taxane-chemotherapy and the level of experimental and standard molecular markets that is important for development of algorithm of treatment tactics for patients with locally advanced breast cancer.

[Sonoelastography in the diagnosis of breast tumors smaller than 2 cm].

This is an analysis of the use of sonoelastography as part of complex instrumental diagnostic procedure (mammography, gray-scale and Doppler ultrasonography) for small breast tumors. A total of 126 patients with breast lesions below 20 mm in diameter were divided into two groups depending on lesion size. The first group consisted of women with 5-10 mm lesions (21 patients with carcinoma and 20 patients with benign tumors), the second group was characterized by 11-20 mm lesions (69 carcinoma patients and 16 patients with benign lesions). According to analysis results the diagnostic complex of gray-scale ultrasonography and sonoelastography is most sensitive, the sensitivity is higher in the second group (89.1% and 97.7% respectively). The complex ultrasonography procedure yielded better overall results than mammography in both patients' groups.

[Use of Taxotere in neoadjuvant therapy of breast cancer].

Wide-range research in the efficacy of neoadjuvant therapy of breast cancer has been conducted worldwide for over two decades. Promising end results have been reported on completion of clinical and pathomorpologic response. It has become a standard practice in managing relatively operable and inoperable breast cancer. However, preoperative chemotherapy in operable disease is still a subject of discussion. For many years anthracycline-based treatment has remained a therapy of choice in the neoadjuvant setting. Higher efficacy of its combined use with taxotere and anthracycline was demonstrated. It was followed by higher rates of complete pathomorphologic response and survival. Besides, regimens using taxotere and target therapies are being investigated. Tentative results suggest that better survival may be achieved due to decreased toxicity profiles.

[The risk of local recurrence after breast-conserving surgery for breast cancer].

Recently, the rates of early stage breast cancers involving breast-conserving therapy have increased due to use of mammography screening. Morever, a patient's desire to keep the breast is now considered to be a factor which determines the surgery tactics. However, there has been so far no consensus on optimal extent of surgery capable of preventing local recurrence. In order to precisely estimate such risk it is essential to take into account factors such as tumor size, surgical margin status and age. Besides, correlations between certain subtypes of breast cancer and various associated risks of local recurrence are to be established. Another important factor is to devise the necessary subsequent radiotherapy.

[The role of nanotechnology in creating novel antitumor agents].

Nanobiotechnology, defined as an arm of a nano-system is a rapidly developing area of medicine. Nanomaterials ranging from 1 to 1000 nm in size offer unique advantages of interaction with biological systems on the molecular level. Nanobiotechnologies can be used in definition, diagnosis and treatment of cancer thus leading to the new development of a new discipline--nanooncology. The potential of nanoparticles to be used in in-vivo tumor visualization, biomolecular profiling of tumor growth factors and targeted drug delivery is being studied. These methods stemming from nanotechnology may soon find a broad application in oncology.

[Role of palliative surgery in complex treatment for disseminated breast cancer].

An assessment was undertaken of survival and prognosis in 30 patients with primary disseminated breast tumors which disintegrated following palliative mastectomy carried out for sanitary purposes. That resulted in significant improvement in general condition, higher hemoglobulin and lowered intoxication which in turn made medication and radiotherapy possible: chemotherapy (4-6 cycles) followed by hormonal therapy (22-73.3%), hormonal therapy (8-26.7%), and radiotherapy for surgical scar (16-53.3%). All patients were followed up for 18 months (median--3.8 years). Tumor progression at different stages was detected in 12 (40%); local recurrences--8 out of them (26.7%). By the time of investigation, 9 (20%) out of 30, had died of tumor progression while 21 (80%) continued their treatment at the Institute's Clinic. Mean survival was 21.5 +/-2.2 months (median--19 (8-60+)). Our method proved effective due to high survival (median--18 months) and significant improvement in quality of life. However, visceral metastases (p = 0.02) and tumor growth duration (p = 0.05) were of prognostic significance. Such characteristics as presence or absence of estrogen and progesterone receptors of tumor, histological pattern, and anemia appeared insignificant, as far as prognosis was concerned. Function chi2 difference was highly significant (Cox) (p = 0.00013).