[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.

[Michael Lazarevich Gershanovich--one of the founders of cancer chemotherapy in Russia].

Michael Lazarevich Gershanovich was born 90 years ago. He has made a significant contribution to foundation and development of chemotherapy for malignant tumors. Doctor of Medical Sciences, Professor, Laureate of the State Prize of the Russian Federation, Honored Scientist of the Russian Federation, Academician of the Russian Academy of Natural Sciences, a member of the Editorial Board of the Journal "Problems in Oncology" ("Voprosy Onkologii), member of the World Club of Petersburgians, a retired lieutenant-colonel Michael Lazarevich, until his last day (16.12.2013), was the head of the Department of Medical Oncology of the N.N.Petrov Research Institute of Oncology, St. Petersburg.

[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.

[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.

[Effectiveness and toxicity of MOPP, ABVD, BEACOPP chemotherapy in first-diagnosed Hodgkin lymphoma with a poor prognosis].

In a retrospective study during the primary mode MOPP to primary patients LH II/IVAB stages with a poor prognosis rate of CR, 5--and 10-year DFS, OS was 69%, 71% and 68%, 74% and 64%, ABVD--76%, 78%, 83% and 68%, BEACOPP-baseline--73%, 97%, 85% and 82%, respectively. When the program ran BEACOPP-baseline it was revealed higher rates of DFS compared with ABVD and MOPP. Higher OS rates were observed in the primary patients treated with BEACOPP-baseline compared with MOPP (p = 0.04). In terms of DFS and OS MOPP regimen did not differ from ABVD. Program ABVD and BEACOPP-baseline had no differences in terms of OS. The frequency of primary refractory forms of LH did not depend on the conducted regimens of PCT. Significantly less recurrences occurred during the regimen of BEACOPP-baseline compared to MOPP and ABVD. BEACOPP-baseline was accompanied by a more pronounced reversible hematologic toxicity. Against the background of the program BEACOPP-baseline, neutropenia of III-IV degree was detected in 32%, ABVD--16%, MOPP--13%.

[Combined use of 99mTc-MIBI scintigraphy and ultrasonography (US) in the diagnosis of axillary lymphatic metastasis in patients with breast cancer].

We aimed to evaluate different imaging strategies for diagnosis of axillary LNMs in patients with primary breast cancer (BC). 168 consecutive patients with primary BC were included in the study. Functional imaging by scintigraphy (AxSc) with 99mTc-MIBI was performed in static and tomography modes 15 min after i/v injection. Focal areas of tracer accumulation in axial region were considered as sings of LNMs. Ultrasound (US) examination of axillary region was performed on 7.5 kH scanner. Nodes with diameter more than 1 cm were considered abnormal. All patients were operated with axial LN dissection and subsequent histological evaluation. Scintigraphic signs of LNMs revealed in 65 patients: 48--true positive, 17--false positive. Among 103 women with normal AxSc results 27 had LNMs and 76--uninvolved nodes. Sensitivity (Sen), Specificity (Sp) and Accuracy (Ac) of AxSc were as follows: 64%, 82% and 74%. Sonography diagnosed LNMs in 74 women: 56 were metastatic on histology while other 18--uninvolved. On the contrary, 19 of 94 US normal sized nodes were metastatic on histology. US had following values when used for diagnosis of axillary LNMs: Sen--75%, Sp--81%, Ac--78%. When LNMs were diagnosed as the combination of concordantly abnormal US and AxSc examinations Sp reached 95%, Sen dropped down to 56% and Ac--to 77%. Another model was based on the assumption that LNMs must be diagnosed in all patients with abnormal US or AxSc examinations. According to this strategy Sen reached 83%, Sp--68% and Ac--74%. Thus, we found comparative accuracy of US and AxSc in diagnosis of axillary LNMs in patients with primary BC. Combination of both modalities can significantly improve sensitivity (83%) or specificity (95%) of final conclusion which is determined by established diagnostic strategy and criteria's that are used for BC diagnosis.

[Combined effect of gemcitabine and lomustine in mice with intracranial transplanted lymphosarcoma LIO-1].

SHR mice with intracranial transplanted lymphosarcoma LIO-1 received a single intraperitoneal gemcitabine injection in maximal tolerated dose of 25 mg/kg or single maximal tolerated oral dose of lomustine, 50 mg/kg. Compared to control group gemcitabine injection increased the mice lifespan 1.4-fold (p < 0,01) and oral lomustine 1.6-fold (p < 0,01). The median lifespan of the mice receiving both gemcitabine and lomustine in maximal dose underwent a significant 3.3-fold increase (p < 0,01) compared to controls (2.4-fold compared to gemcitabine and 2.1-fold compared to lomustine group). Combined therapy didn't cause an increase of toxicity.

[Primary refractory and relapsed Hodgkin lymphoma with unfavorable prognosis].

In this retrospective clinical study 100 patients with primary unfavorable prognosis stage II Hodgkin lymphoma (HL) (n = 50) or stage IV HL (n = 50). The ABVD chemotherapy allowed to achieve remission in 90% of cases with 5-year relapse-free survival (RFS) and overall survival (OS) of 64% and 92%, the basic BEACOPP regimen lead to the same 90% remission rate with 74% DFS and 94% OS. These results for ABVD and basic BEACOPP regimens are characterized by similar statistic values (p = 1.0; p = 0.6; p = 0.9), although the use basic BEACOPP lead to statically valid decrease of grade III-IV toxicity (p = 0.005). The occurrence of primary refractory HL was slightly higher in basic BEACOPP group (18% versus 10% in ABVD group), although this difference had no statistical value (p = 0.3) and was probably due to higher number of patients with > 1 extranodal localizations. The occurrence of primary refractory HL correlated to disease stage: 6% in stage II and 22% in stage IV (p = 0.04). HL relapse frequency in ABVD and BEACOPP groups was similar (12% and 8%), there was no statistically valid difference (p = 0.5). In ABVD and basic BEACOPP recipients with stage II/IV HL the primary refractory disease rate was 15%, relapse rate was 10%. Five-year OS in primary refractory and relapsed patients was lower, than in general patient population (64% and 70% compared to 80%), although the difference had no statistical significance (p = 0.6, p = 0.7).

[Primary-refractory forms of Hodgkin's lymphoma].

Retrospective analysis defined risk factors of primary-refractory course of Hodgkin's lymphoma as well as adverse prognostic factors, efficacy of I and II therapy lines in patients with primary-refractory forms of Hodgkin's lymphoma. By means of discriminant analysis risk factors were as follows: massive tumor lesion, chemotherapy as compared to chemoradiotherapy in the I line, intoxication symptoms, IPS > or = 3, LDH level more than 1,5xULN, late beginning of specialized treatment (over 12 months from initial symptoms of disease), damage of 5 and more areas of lymph nodes, age more than 45 years, increase of ESR higher than 30 mm/h in Stage B and 50 MM/H in Stage A, Stage IV of disease, leukocyte rate higher than 15 x 10(9)/l, presence of more than one extranodal lesion. As a result there were revealed 4 prognostic factors unfavorably influencing on survival rates in primary-refractory forms of Hodgkin's lymphoma with originally Stages II/IV with poor prognosis. The worst 5-year survival rates were found in the presence of 3 and 4 adverse prognostic factors. These circumstances should be taken into consideration choosing optimal treatment and predicting of success of the proposed treatment.

[Methodologic aspects of radionuclide diagnosis of breast cancer with 99mTc-MIBI].

The aim was to study the diagnostic possibilities of breast scintigraphy with help of domestic RFP tehnetril labeled 99mTc. Breast scintigraphy was performed in 132 women at age between 32 and 68 years. Visualization of both breasts in planned mode was performed in the lateral and anterior projections in 10-15 minutes after intravenous injection of 740-860 MBq of 99mTc-tehnetril. After this, a study was conducted in the mode emission computed tomography. Morphological verification of changes in the breast was performed in all cases. Sensitivity, specificity and overall accuracy of planar breast scintigraphy was 96% (105/112), 94% (245/252) and 95% respectively. Upon planar study of 132 breasts suspicious on cancer presence breast scintigraphy showed not high specificity 68% (7/21), sensitivity reached 94% (105/112), overall accuracy--90%. SPECT did not show visible benefits: sensitivity-92% (100/112), specificity--75% (5/21), and overall accuracy--89%. Usage of a semi-quantitative accrual rate of RFP in tumor allowed distinguishing four groups of patients with different, to breast scintigraphy data, likelihood of breast cancer (from 2-10% to 96%). As a result current methods of breast scintigraphy provide high sensitivity (88-96%) and accuracy in breast cancer detecting of any size as far as the use of additional diagnostic criteria, semi-quantitative ratio RFP accumulation in tumor in particular, can significantly increase (up 94%), specificity of diagnostic conclusions.

[Investigation of gemcitabine plus lomustine treatment in mice with transplantable lymphosarcoma LIO-1].

Efficiency of gemcitabine plus lomustine treatment of transplantable lymphosarcoma LIO-1 in mice was significantly higher than that of monotherapy. According to the area under the kinetic curve for tumor growth, antitumor action, for single maximum tolerable dose of gemcitabine 25 mg/kg body, rose 4.6 times (p < or = 0.001), for lomustine 50 mg/kg body,--2.9 times (p < or = 0.01). The combination involved moderately increased toxicity. Lethality rate for gemcitabine+lomustine, 50 mg/kg body each, was as low as one and a half times as compared with gemcitabine therapy alone, 50 mg/kg body, (30 and 20%, respectively). The antitumor action of the combination (50 mg/kg body), was 32 times that of gemcitabine 50 mg/kg body (p < or = 0.001) and lomustine 50 mg/kg body--30 times (p < or = 0.001).

[Synergism of antitumor activity of gemcitabine and dioxadet in mice with ascitic Ehrlich's tumor].

Antitumor activity of a new cytostatic drug combination of gemcitabine and dioxadet have been studied in 86 female SHR mice transplanted with 5 x 10(6) of ascitic Ehrlich's tumor cells each. All mice received a single injection of gemcitabine, dioxadet on combination 48 hams after tumor cells introduction. In first series, experimental animals received maximal tolerable dose of gemcitabine (25 mg/kg) and one half of dioxadet maximal tolerable dose (2.5 mg/kg). In the second series of experiments, the animals received 5 mg/kg of dioxadet along with the same gemcitabine dose. Effect of drugs was compared using the time to ascites detection, body weight increase, and survival time. Gemcitabine and dioxadet administered separately and in combination inhibited the growth of ascitic Ehrlich's tumor in the mice. In both series of experiments antineoplastic activity of gemcitabine and dioxadet combination was significantly higher in comparison to the control groups receiving these drugs separately. The highest antineoplastic activity of the gemcitabine and dioxadet combination was observed when the maximal tolerable doses of both drugs was applied. However, the tumor cells growth was also significantly inhibited in mice receiving half of dioxadet dose. Synergism of antitumor activity of gemcitabine and dioxadet was not accompanied by appreciable increase in toxicity.

[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.

[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.

[Gemcitabine plus cisplatin therapy in breast cancer refractory to anthracyclines, docetaxel and capecitabine].

The efficacy and tolerability of therapy with gemcitabine plus cisplatin were evaluated in 49 patients with disseminated breast cancer refractory to anthracyclines, docetaxel and capecitabine. Gemcitabine 600-750 mg/m2 and cisplatin 30 mg/m2 were injected intravenously, dropwise, on days 1 and 8 of a 3-week course. Overall response rate was 27%; median response duration - 8.0 months, median mediation time until tumor progression--3.2 months, and median survival time--10.3 months. Untoward side-effects were moderate, reversible and, therefore, did not require dosage to be corrected or cut down.