[Prevalence of widespread BRCA1 gene mutations in patients with familial breast cancer from St. Petersburg].

Ten variants different from the canonical nucleotide sequence (GenBank, U14680) has been identified when studying the mutation spectrum in gene BRCA1. Six of them (5382insC, 2963del10, 3819de15, 3875del4, 2274insA, and R1203X) cause premature termination of protein synthesis, thus predisposing to breast cancer. A missense mutation E1250K is presumed to be a factor of predisposition to cancer. We classified three variants of nucleotide sequence found in some patients as DNA polymorphisms S694S, L771L, and E1038G. The 5382insC and 3819de15 mutations have been detected in four and two families, respectively. Five of the mutations detected have not been found in Russia before. However, all mutations except for 2963del10 have been found in other populations of the world, which indicates their long evolutionary history. Two mutations found in patients from St. Petersburg (5382insC and 3875de14) have also been found in oncological patients from other regions of the Russian Federation.

[Search for frequently encountered mutations in genes predisposing to breast cancer]. / Poisk chasto vstrechaiushchikhsia mutatsii v genakh predraspolozhennosti k raku molochnoi zhelezy.

DNA of oncological patients, including Ashkenazi Jews and Slavs, living in St. Petersburg was collected, and the resultant collection was screened for three common mutations of genes BRCA1 and BRCA2 by means of heteroduplex analysis. The mutation 5382insC in exon 20 of the BRCA1 gene was found in four unrelated patients, including three Slavs and one Ashkenazi Jew, with a positive family history of breast cancer. The mutations 185delAG and 6174delT in the BRCA1 and BRCA2 genes, respectively, which are typical of Ashkenazi Jewish patients with breast cancer, were not found in the patients of either ethnicity living in St. Petersburg, although the 6174delT mutation was found in the control group of Ashkenazi Jews. A new 12-nucleotide duplication g.71741ins12nt found in intron 20 of the BRCA1 gene was described. The high frequency of the 5382insC mutation in the BRCA1 gene in patients with familial breast cancer in both St. Petersburg and Moscow indicates that Russian families with the history of breast cancer should be primarily tested for this mutation.

[Cytogenetic markers in blood lymphocytes from members of a family with high predisposition to breast cancer]. / Tsitogeneticheskie markery limfotsitov krovi u chlenov sem'i s vysokoi predraspolozhennostiiu k raku molochnoi zhelezy.

A medico-genealogical study was concerned with a line consisting of 38 members. Four of 18 women had breast cancer (BrCr) and one-leukemia. BrCr was diagnosed in the 1st generation in the proband's grandmother (1-2) at the age of 40 and in the 3rd generation: in the proband (III-8) at the age of 43 and in two of her sisters at the age of 44 (III-2) and 48 (III-10), respectively. Breast tumors appeared in the 3rd generation patients approximately at the same age. A cytogenetic study of venous blood lymphocyte metaphases using G-banding of chromosomes revealed homogeneously-stained regions in 100% of cells in the proband's chromosome I: (q11-q12). In the proband's asymptomatic daughter (IV-9), pronounced chromosomal instability (ruptures in chromosomes and chromatids in 50% of cells) was observed. Also, single and multiple double minutes were detected in 10% of cells, while marker 14(p12-pter)-in 100%. This marker was also identified in 100% of lymphocytes taken from the asymptomatic daughter (IV-11) of the proband's sister (III-10). The nature and significance of cytogenetic markers detected in blood lymphocytes of the proband and said siblings are discussed. Heritability of said cytogenetic markers pointing to predisposition to cancer development (of BrCr in said family) is suggested.

[Ultrasound differentiation of fibroadenoma and diagnosis of minimal carcinoma of the breast]. / Ekhograficheskie varianty fibroadenomatoza i diagnostika minimal'nykh kartsinom molochnoi zhelezy.

The investigation was based on the ultrasound and mammographic examination of 630 patients with different patterns of fibroadenoma and 23--with carcinoma of the breast. Sonography should be carried out in step with menstrual cycle when diffuse hyperplasia of glandular tissue is registered. Minimal lobular cancers present most difficulties. Detection of a "node" should not be seen as the dividing line between tumor and fibroadenoma. In cases of fibroadenoma, sonography should be sometimes supplemented by mammography. Fine-needle aspiration biopsy should be used to clarify radiological evidence.

[Adjuvant chemotherapy with anthracyclines in comparison with the standard combination of CMF in breast cancer with high risk of relapse]. / Antratsiklin-soderzhashchaia ad''iuvantnaia khimioterapiia v sravnenii s klassicheskoi skhemoi CMF u bol'nykh rakom molochnoi zhelezy s vysokim riskom retsidiva.

The effectiveness of adjuvant therapy with adriablastin and doxorubicin for breast cancer has been compared to that of standard CMF. During 1985-1990, the study included 349 patients with T1-2N2M0 and T3N0-2M0 tumors; mean age--46 yrs; mean follow-up--96.7 months. Overall survival rate in the doxorubicin group was 73%, CMF--62%; relapse-free survival--62.1 and 55%, respectively. The absolute difference in overall survival rates (11%) proved barely significant (p = 0.056). However, the difference in overall survival (p < 0.05) after anthracyclines and CMF in patients with tumors T1-2N2M0 and T3N1M0 was significant and in favor of the former. As far as frequency and degree of side-effects is concerned, their patterns were practically identical in both groups, except for the significantly higher frequency of cardiotoxity and complete alopecia in doxorubicin therapy. Cardiotoxic complication rate was significantly reduced from 13.8 to 3.9% by cardioxane treatment.