The identification of BRCA1/2 and CHEK2 germline mutations is central to the molecular diagnostics of susceptibility to breast or/and ovarian cancer. A microarray-based rapid genotyping technique has been developed for identifying BRCA1 (185delAG, 300T > G, 4153delA, 5382insC, and 4158 A > G, 5382insC), BRCA2 (695insT and 6174delT), and CHEK2 (1100delC) mutations. It was applied for 412 randomly collected breast-cancer specimens from central Russia. In 25 (6.0%) patients, breast cancer was associated with other tumors of, e.g., ovarian, cervical, or colorectal cancer. BRCA1/2 and CHEK2 mutations were detected in 33 breast-cancer patients (8.0%). The most frequent mutations were BRCA1 5382insC, which was found in 16 patients (3.9%), and CHEK2 1100delC, which was detected in seven patients (1.7%). The suggested diagnostic microarray proved to be an efficient means of identifying BRCA1/2 and CHEK2 founder mutations most frequent in central Russia and can be proposed as a high-throughput diagnostic tool for clinical genetic testing.

Tamoxifen is one of the basic drugs of adjuvant hormone therapy in patients with hormone-dependent breast tumors. The purpose of this paper is to analyze the results of randomized trials of long-term adjuvant hormone therapy for breast cancer.

Выявление герминальных мутаций в генах BRCA1/2 и CHEK2 составляет основу молекулярной диагностики предрасположенности женщин к раку молочной железы и яичников. Нами разработана методика быстрого генотипирования мутаций в гене BRCA1 (185delAG, 300T>G, 4153delA, 4158 A>G, 5382insC), гене BRCA2 (695 insC, 6174delT) и гене CHEK2 (1100delC) с использованием биочипов. Протестировано 412 больных РМЖ, из случайной выборки (без учета семейной истории) по Центральной России. У 25 (6.0%) из них рак молочной железы диагностирован в составе первично-множественных злокачественных новообразований (рак яичников, колоректальный рак, рак шейки матки и т.д.). Мутации BRCA1/2 и CHEK2 определены у 33 (8.0%) больных РМЖ. Наиболее часто встречаются мутации 5382insC в гене BRCA1 (3.9% от общего числа пациенток) и 1100delC в гене CHEK2 (1.7% соответственно). Предлагаемый метод эффективен при обнаружении наиболее распространенных в Центральной России герминальных мутаций в генах BRCA1/2 и CHEK2 , что позволяет использовать его в качестве высокопроизводительного диагностического инструмента в клинической онкологической практике.

Relation between biochemical markers of bone resorption (urine excretion of deoxypyridinoline – Dpyd, serum concentration of C-telopeptide of type I collagen – СТX and activity of tartrate-resistant acid phosphatase 5b – TRAP 5b and formation (bone-specific alkaline phosphatase – BAP) and a range of skeletal complications were evaluated in 239 breast cancer patients with and without bone metastases. The elevation of studied biochemical parameters in breast cancer patients was significantly associated with the extent of skeletal metastases (CTX, BAP), pathological fractures (CTX, TRAP, BAP) and the severity of pain (CTX, Dpyd, TRAP, BAP). Elevated rate of bone turnover was associated with reduced survival of breast cancer patients. The significant difference of overall survival and progression-free survival estimated on a base of cut-off values of CTX (0.74 ng/ml) and BAP (43.7 IU/L) was found in the group of breast cancer patients with bone metastases. Elevated CTX and BAP were associated with reduced relapse free survival in patients without bone metastases. These biochemical parameters are of value in the bone diseases prognosis and management of breast cancer patients.

Psychological impact of modified radical mastectomy carried out simultaneously with breast reconstruction (n=45) was compared with that in controls who underwent similar surgery for cancer alone (n=50). After 12 months, depression was less frequent in group 1 and indices such as being a good mixer, joyfulness, activity, happiness, job satisfaction and access to leisure and entertainment were significantly higher than among controls (p< or =0.05). However, deep depression persisted in group 1 (13%) as long as for 12 months and intense angst in 17.8%.

The report deals with retrospective research in possible induction of relapse by breast reconstruction carried out simultaneously with surgery for breast cancer. The end results were compared between cases of modification of radical mastectomy combined with reconstruction (n=124) and controls who underwent surgery for cancer alone (n=379). Standard radio- and systemic therapy was used. Median follow-up was 64 months. Local and general recurrence as well as relapse-free and overall survival rates were identical. Multivariate analysis failed to establish any correlation between primary breast reconstruction and relapse. Nor did it increase the risk of the development of the latter.

The investigation was concerned with use of 99mTc-methoxyisobutyl isonitrile (99m Tc-MIBI)-assisted prognosis for chemotherapy of locally-advanced breast cancer based on the assessment of 99m Tc retrieval from primary tumor in 26 patients. 99mTc was administered in the course of two-phase scintigraphy of the breast prior to chemotherapy. The dynamics of accumulation and withdrawal from tumor was identified. In view of the absence of any correlation between accumulation and chemotherapy efficacy, one was established between high rates of label withdrawal, on the one hand, and lack of pathomorphosis, on the other, while medium and low rates were associated with marked pathomorphosis in 44 and 50%, respectively (p < 0.05).

High-dose chemotherapy using transplantation of hemopoietic precursor cells offers much advantage for treatment of prognostically unfavorable cancers of the breast. Both experimental and clinical evidence points to a potential of raising antitumor effect by increased dosage of chemical drugs. Clinical studies using high-dose chemotherapy for treating patients with stage II-III tumors or with greater than or equal to 10 positive axillary lymph nodes, and locally-advanced and disseminated tumor established a relative rise in overall and recurrence-free survival, as compared with standard treatment. Hazardous cytopenia and related complications can be significantly reduced when hemopoietic precursor cells are transplanted from peripheral blood.

A retrospective analysis of the end results of surgical treatment of 1.417 patients with T1-2N0-1M0 breast tumors is presented: local recurrence after radical surgery (1.151)-2.4% after radical resection (165)-5.5%, and after lumpectomy combined with axillary lymphadenectomy (101)-4.0%. In the T1N0M0 group, the end results of radical resection and radical mastectomy were identical. In the T1N0M0 and T2N0M0 groups, in which lumpectomy combined with axillary lymphadenectomy was performed, the end results were inferior to those radical mastectomy. There was a correlation between tumor cell detection in the blood and lymph vessels and extent of intervention: radical mastectomy-6%; radical resection-13% and lumpectomy combined with axillary lymphadenectomy-17%. The latter index tended to rise in cases of recurrence after breast-conserving surgery.

Different procedures of breast reconstruction were employed in the treatment of 223 breast cancer patients (primary reconstruction-97; delayed reconstruction-136). No major complications were recorded, including total necrosis of transverse abdominal island flap. The advantage offered by the latter is due to its resistance to chemoradiotherapy: complications such as boundary necrosis do not destroy cosmetic effect as in the case of expander application.