Association between estrogen receptor gene polymorphisms and breast density in postmenopausal women.

Objectives The aim of this study was to evaluate the association between clinical characteristics and polymorphisms HaeIII, MspI and XbaI of the estrogen receptor gene alpha with postmenopausal mammographic density. Methods A prospective study was performed with 120 women who were not users of hormones and had no identified breast lesions. All of them underwent bilateral mammography; the radiological density was determined by three independent observers, with two subjective evaluations based on the ACR-BIRADS(R) classification of mammographic patterns, 2003, and one computerized evaluation using the gray-scale histogram tool of the Adobe Photoshop(R) 7.0 software. Peripheral blood samples were obtained for DNA extraction, performed according to the GFX(R) Kit protocol (Amersham-Pharmacia). Polymerase chain reaction restriction fragment length polymorphism was carried out for an analysis of the polymorphisms present in intron 1 (HaeIII and XbaI) and in exon 1 (MspI) of the estrogen receptor gene. Results There was a high degree of concordance among the observers in the determination of mammary density (Kappa, Pearson and Spearman, p < 0.001). The associations of clinical characteristics with mammary density were: age (p = 0.04), body mass index (p < 0.0001) and age at menarche (p = 0.02). The relationship between the allele distribution of the polymorphisms and density was: XbaI (p = 0.02), HaeIII (p = 0.65) and MspI (p = 0.65). Conclusions Our data suggested that the polymorphism XbaI may be strongly related to mammographic density.

Analysis of human mammary fibroadenoma by Ki-67 index in the follicular and luteal phases of menstrual cycle.

OBJECTIVES: Fibroadenoma is the most common benign mammary condition among women aged 35 or younger. Expression of Ki-67 antigen has been used to compare proliferative activity of mammary fibroadenoma epithelium in the follicular and luteal phases of the menstrual cycle. MATERIALS AND METHODS: Ninety eumenorrheic women were selected for tumour excision; they were assigned to either of the two groups, according to their phase of menstrual cycle. At the end of the study, 75 patients with 87 masses were evaluated by epithelial cell Ki-67 expression, blind (no information given concerning group to which any lesion belonged). RESULTS: Both groups were found to be homogeneous relative to age, menarche, body mass index, previous gestation, parity, breastfeeding, number of fibroadenomas, family history of breast cancer and tabagism. Median tumour size was 2.0 cm and no relationship between proliferative activity and nodule diameter was observed. No typical pattern was observed in the expression of Ki-67 in distinct nodules of the same patient. Average values for expression of Ki-67 (per 1000 epithelial cells) in follicular and luteal phases were 27.88 and 37.88, respectively (P = 0.116). CONCLUSION: Our findings revealed that proliferative activities in the mammary fibroadenoma epithelium did not present a statistically significant difference in the follicular and luteal phases. The present study contributes to clarifying that fibroadenoma is a neoplasm and does not undergo any change in the proliferative activity during the menstrual cycle.

Bcl-2 oncogene expression in estrogen receptor-positive and negative breast carcinoma.

PURPOSE: The aim of this study was to evaluate Bcl-2 oncogene expression in estrogen receptor (ER)-positive and negative breast carcinomas. METHODS: A study involving 72 cases of infiltrating ductal carcinoma of the breast in postmenopausal women divided into two groups: Group A (ER positive, n=37) and Group B (ER negative, n=35). Immunohistochemical analysis of bcl-2 expression was carried out semiquantitatively based on the percentage of stained tumoral cells and the intensity of staining. The chi-square test was used in the statistical analysis of the data and significance was established at p < 0.05. RESULTS: Bcl-2 oncogene expression was statistically greater in tumors of Group A (59.5%) compared to those of Group B (8.6%), (p < 0.001). CONCLUSION: Bcl-2 had a significantly greater expression in the ER-positive breast tumors compared to ER-negative tumors.

Effects of low dose tamoxifen on normal breast tissue from premenopausal women.

The aim of this study was to determine the effects of low doses of tamoxifen (5 and 10mg/day) for 50 days compared with the standard dose (20 mg/day) on breast biomarkers measured in normal breast tissue from premenopausal patients. A randomised double-blind study was performed using tissue from 56 premenopausal women with a diagnosis of fibroadenoma of the breast. Excisional biopsy was performed on the 50th day of therapy. Normal breast tissue samples were collected during surgery. The patients were divided in groups: A (placebo, n=11); group B (5 mg, n=16), group C (10 mg, n=14) and group D (20 mg, n=15). In this cross-sectional study, differences in the expression of Oestrogen Receptor alpha (ERalpha), Progesterone Receptor (PR), Ki-67, apoptotic bodies and mitotic index between the different groups after treatment can be seen on the normal breast tissue. We believe that a lower dose of tamoxifen could reduce the side-effects associated with treatment without affecting its chemopreventive activity in the breast.

Estrogenic activity of tamoxifen on normal mammary parenchyma in the luteal phase of the menstrual cycle.

OBJECTIVES: Tamoxifen, an anti-estrogenic drug used in the adjuvant treatment of breast cancer, deserves more investigation for the determination of its efficacy as a prophylactic agent against breast cancer in high risk women. Thus, the action of tamoxifen on the human mammary gland was studied by measuring the number of lysosomes in normal mammary epithelium during the administration of tamoxifen. METHODS: Tamoxifen was administered only during the luteal phase of the menstrual cycle to avoid interference with corpus luteum formation. A fragment of breast tissue adjacent to a fibroadenoma was obtained during surgery from 35 premenopausal women aged 15 to 37 years who had been eumenorrheic for at least 6 months; 18 of these patients were treated with tamoxifen and 17 were used as controls. Lysosome counts were performed under the light microscope on slides submitted to the acid phosphatase cytochemical technique and the data were analyzed statistically by the Mann-Whitney test. RESULTS: The fragments from the group treated with tamoxifen showed a significant decrease in lysosome numbers. CONCLUSIONS: Tamoxifen administered after ovulation significantly decreases the number of lysosomes in the cells of normal mammary epithelium, demonstrating the antiestrogenic effect of the drug on this target tissue.