HER-2 [Ile655Val] polymorphism in association with breast cancer risk: a population-based case-control study in Slovakia

Breast cancer belongs to the most frequent types of cancer affecting women and it occurs at any age. Around 1600-1800 women are getting ill annually in the Slovak republic. One of the most important factors in connection with cancer genesis refers to changes in specific genes. HER-2 proto-oncogene belongs to low penetrating genes, which increase susceptibility to breast cancer genesis. Clinical studies demonstrated an association between polymorphism at codon 655 of this gene and increased risk for breast cancer development. The aim of this case-control based prospective study was to determine the distribution of HER-2 genotype and its association with risk factors of breast cancer in the population of women in Slovak republic. HER-2 genotypes were determined with PCR-RFLP method. The DNA was isolated from white blood cell nuclei. The frequency of Val allele in the cancer group was 29.79% and was higher than in the control group 15.84% (p<0.05). The presence of the heterozygote (Ile/Val) genotype was identified in 46.81% of patients in the case group and in 28.33% in healthy individuals, and the homozygote (Val/Val) genotype in 6.38% and 1.67, respectively (p<0.01). The risk of breast cancer development for carriers of one valine (Val) allele in genotype was two-times lower (OR=2.47) than for carriers of two Val alleles (OR=5.73) (p<0.05). Risk of cancer genesis for Val allele carriers was higher in multiparas (OR=2.90), among women with positive family history of breast cancer (OR=5.0), BMI>24 (kg/m2), and late menopause (OR=1.5). Contraceptives in anamnesis contrariwise showed tend to decrease the risk in Val allele carriers (OR=0.3). In conclusion, this study revealed relatively high frequency of the Val allele among the women population of the Slovak republic. Ile655Val polymorphism of HER-2 gene was associated with a statistically significantly increased risk of breast cancer all above in homozygotes for Val allele.     

Cystic hypersecretory carcinoma: rare and poorly recognized variant of intraductal carcinoma of the breast. Report of five cases

AIMS: To report five cases of a rare variant of intraductal carcinoma of the breast, so-called cystic hypersecretory carcinoma. The clinical and pathological characteristics of the lesion are described, along with a review of the literature. METHODS AND RESULTS: The patients were females aged between 53 and 78 years (average 66.8 years). The size of the lesions ranged between 70 and 80 mm in largest dimension. In two cases, the development of high-grade invasive ductal carcinoma was observed; in one additional case there was recurrence of high-grade in-situ carcinoma after 3 years. This emphasizes the importance of correct diagnosis of this potentially aggressive lesion. Strong over-expression of HER-2/neu protein was observed in three cases, including the two with an invasive component. Protein p53 was variably positive in all cases. Steroid receptor immunohistochemistry yielded variable results with only one case being positive for both oestrogen and progesterone receptors. Interestingly, in most cases (4/5) staining for androgen receptors was observed. CONCLUSIONS: Cystic hypersecretory ductal carcinoma of the breast is a rare distinctive variant of ductal carcinoma in situ. It has the potential for invasive growth and the development of metastases.     

Young Barley Indicates Antitumor Effects in Experimental Breast Cancer In Vivo and In Vitro

The effect of dietary administered young barley containing a mixture of phytochemicals to female rats for the prevention of N-methyl-N-nitrosourea-induced mammary carcinogenesis was evaluated. After carcinogen administration (14 wk), mammary tumors were removed and prepared for histopathological and immunohistochemical analysis. Moreover, in vitro evaluation of possible mechanisms in MCF-7 breast cancer cell line was performed. Barley (0.3%) demonstrated mild antitumor effect in mammary carcinogenesis, yet 3% barley did not further improve this effect. Immunohistochemical analysis of rat tumor cells in treated groups showed significant increase in caspase-3 expression and significant reduction in Ki67 expression. In addition, 3% barley significantly decreased dityrosine levels versus control. Barley in higher dose significantly decreased serum low-density lipoprotein-cholesterol in rats. In vitro studies showed that barley significantly decreased survival of MCF-7 cells in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and significantly decreased 5-bromo-20-deoxyuridine incorporation versus control. Barley prevented cell cycle progression and extended incubation with barley showed significant increase in the percentage of annexin V/propidium iodide-positive MCF-7 cells. Our results propose an antitumor effect for the mixture of phytochemicals present in young barley in a breast cancer model.     

Mammary carcinoma with osteoclast-like giant cells--report of two cases

Authors describe two cases of a rare type of mammary carcinoma occurring in 47-year and 49-year-old women, characterised by osteoclast-like giant cells, hypervascular stroma, and signs of older and recent haemorrhages on the background of the conventional type of breast carcinoma. In both cases there was diagnosed moderately differentiated ductal invasive carcinoma with osteoclast-like giant cells, which were present in tumorous stroma as well as scattered between tumorous cells. Immunohistochemical analysis (vimentin and CD68 positivity and negativity of cytokeratins, EMA and S-100 protein) confirmed a histiocytic origin of these giant cells as well as their reactive non-neoplastic nature. Clinical and morphological features of this unusual type of breast carcinoma indicate that it should be regarded as an unique clinical- histomorphological entity with probably better prognosis when compared to ductal invasive carcinoma not otherwise specified and it should not be included among metaplastic breast carcinomas.     

Rapidly growing nodular pseudoangiomatous stromal hyperplasia of the breast in an 18-year-old girl

Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a rare benign proliferation of mesenchymal stromal cells with irregular slit-like formations resembling angiomatous structures. In the majority of cases this lesion is a focal microscopic finding in breast biopsies performed for benign or malignant diseases. It may present in a pure diffuse or nodular form. The exact etiology and pathogenesis of this tumor-like lesion is still unknown, but a proliferative response of myofibroblasts to hormonal stimuli has been postulated. A large 12 x 9 x 3.5 cm rapidly growing nodular form of PASH of the breast in an 18-year-old woman is here described with clinical and histological findings. A possible hormonal etiology was indicated by elevated progesterone (three-fold) and decreased estrogen serum levels. Different diagnostic lesions, such as giant fibroadenoma and low-grade angiosarcoma, are discussed. To the authors' knowledge this is only the fourth case of nodular PASH of the breast reported in the English literature.     

Tumor-like manifestation of endosalpingiosis in uterus: a case report

We report on a 50-year-old female patient affected by breast cancer and a tumorous lesion located in the subserosal and intramural part of the uterine fundus. It consisted of glandular and cystic forms lined with epithelium of the tubal type. We describe the clinical, macroscopic, and histological features of this rare non-neoplastic lesion, classified as florid endosalpingiosis (ES) and belonging to the spectrum of Müllerian lesions. The discussion focuses on its morphological characteristics, the differential diagnosis, and the potential reasons leading to its origin. To the best of our knowledge, this is the fifth case of florid ES of uterus reported in the English literature.