Breast carcinoma is the most common malignancy among women and it has a major impact on mortality. Studies of primary chemoprevention with tamoxifen have generated high expectations and considerable success rates. The efficacy of lower doses of tamoxifen is similar to that seen with a standard dose of the drug, and there has been a reduction in healthcare costs and side effects.The immune reaction to monoclonal antibody Ki-67 (MIB-1) and the expression of estrogen receptors (1D5) and progesterone receptors (PgR 636) in breast carcinoma were studied in patients treated with 10 mg of tamoxifen for a period of 14 days.A prospective randomized clinical trial was conducted with 38 patients divided into two groups: Group A: N = 20 (control group-without medication) and Group B: N = 18 (tamoxifen/10 mg/day for 14 days). All patients signed an informed consent term previously approved by both institutions. Patients underwent incisional biopsy before treatment and 14 days later a tumor tissue sample was obtained during surgical treatment. Positivity was quantitatively assessed, counting at least 1.000 cells per slide. For statistical data analysis, a Wilcoxon non-parametric test was used, and α was set at 5%.Both groups (A and B) were considered homogeneous regarding control variables. In Group A (control), there was no statistically significant reduction in Ki-67 (MIB-1) (p = 0.627), estrogen receptor (1D5) (p = 0.296) and progesterone receptor positivity (PgR 636) (p = 0.381).In Group B (tamoxifen 10 mg/day), the mean percentage of nuclei stained by Ki-67 (MIB-1) was 24.69% before and 10.43% after tamoxifen treatment. Mean percentage of nuclei stained by estrogen receptor (1D5) was 59.53% before and 25.99% after tamoxifen treatment. Mean percentage of nuclei stained by progesterone receptor (PgR 636), was 59.34 before and 29.59% after tamoxifen treatment. A statistically significant reduction was found with the three markers (p < 0.001).Tamoxifen significantly reduced monoclonal antibody Ki-67 (MIB-1), estrogen receptor (1D5) and progesterone receptor positivity (PgR 636) in the breast epithelium of carcinoma patients treated with a 10 mg dose of tamoxifen for 14 days.

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The purpose of this study was to study the monoclonal antibody MIB-1 in the normal breast epithelium adjacent to a fibroadenoma in women in the luteal phase of the menstrual cycle who were treated with tamoxifen at doses of 10 and 20 mg for 22 days. The proliferative activity of the mammary epithelium adjacent to the fibroadenoma was studied by immunohistochemistry on the basis of the monoclonal antibody MIB-1 (Immunotech, catalog No. 0505, lot 001). The study was randomized and double blind and was conducted on 44 women with fibroadenomas divided into three groups: A (n=16, placebo), B (n=15, tamoxifen, 10 mg), and C (n=13, tamoxifen, 20 mg). Tamoxifen was administered for 22 days starting on the 2nd day of the menstrual cycle, and a biopsy was taken on the 23rd day. Serum estradiol, progesterone, sex hormone binding globulin, follicle-stimulating hormone, luteinizing hormone, and prolactin were measured before treatment (21st and 24th day of the previous menstrual cycle) and on the day of the biopsy. The mean percentage of stained nuclei per 1,000 cells was 9.2 in group A, 4.5 in group B, and 3.2 in group C. The Fisher's test revealed that tamoxifen significantly reduced MIB-1 at doses of 10 and 20 mg compared with the placebo group (p < 0.0001), with no significant differences between doses in terms of proliferative activity (p=0.21). Groups B and C presented a significant increase in progesterone (p=0.038), estradiol (p < 0.001), and sex hormone binding globulin (p=0.001) levels. Elevation of serum follicle-stimulating hormone concentration (p=0.0045) and a fall in prolactin levels (p=0.0055) were observed. We conclude that tamoxifen significantly reduced the proliferative activity of the mammary epithelium at the doses of 10 and 20 mg/day.

109Relato de Caso 21 (2): 109-111, 1999 RBGO Introdução O tumor filodes, também denominado cystosarcoma phyllodes em razão das projeções foliácias de tecido tumoral no interior de cavidades císticas, é uma neoplasia mista de tecido epitelial e conectivo, caracterizando-se por um crescimento rápido e podendo apresentar grandes dimensões no momento do diagnóstico 1,3,7,8,9 . É um tumor raro, representando 0,5% de todos tumores mamários. A recidiva é freqüente porém raramente metastatiza e, quando isto ocorre, geralmente é por via hematogênica. A bilateralidade

[1][2][3] . Entretanto, pouco se sabe a respeito dos efeitos da droga no tecido mamário normal, tanto na dose usual empregada no tratamento adjuvante do câncer de mama, como em doses menores. O tamoxifeno, droga antiestrogênica não esteroídi-ca, é um isômero trans, derivado trifeniletilênico com efeito antiestrogênico e agonista parcial dos estrogênios, facilmente absorvido por via oral na forma do sal citrato. É metabolizado pelo citocromo P450 no sistema microssomal hepáti-co, resultando em vários metabólitos [4][5][6] . O tamoxifeno e seus similares atuam de modo complexo como antagonistas estrogênicos nas células normais e malignas da mama, e agonistas estrogênicos em outros tecidos do corpo, como ossos, útero e sistema cardiovascular. A atuação da droga é mediada pelos receptores estrogênicos celulares por meio de várias reações complexas [7][8][9][10][11] . A proliferação celular pode ser estudada por vários métodos, como: figuras de mitose, citometria de fluxo, índice de incorporação de timidina, bromodeoxiuridina e por vários marcadores de proliferação, empregando-se mé-todos imuno-histoquímicos.O MIB-1 é um anticorpo largamente utilizado no estudo da proliferação celular, que reage com uma proteína (antígeno) nuclear não-