Search

The objective of this study was to evaluate the effects of raloxifene on normal breast tissue. A randomized, double-blind study was carried out in 30 ovulatory, premenopausal women of 18-40 years of age, who had been diagnosed with fibroadenoma of the breast. The patients were divided into two groups: Group A (placebo, n = 16) and Group B (raloxifene 60 mg, n = 14). The medication was given for 22 days, beginning on the first day of the menstrual cycle. An excisional biopsy was carried out on the 23rd day during which a sample of normal breast tissue was collected to evaluate the presence of the proliferating cell marker Ki-67. Student's t-test was used for the statistical analysis of data (p < 0.05). Mean percentage of stained nuclei in groups A and B was 10.96 +/- 1.27 and 1.21 +/- 0.26, respectively (p < 0.001). Raloxifene significantly reduced the proliferative activity of normal breast tissue in premenopausal women.

For almost three decades, tamoxifen has been used in the adjuvant treatment of breast cancer. It has also proven effective in the chemoprophylaxis of this disease and in the treatment of cyclic mastalgia. Since a fibroadenoma is a benign hormone-dependent neoplasm which contains estrogen receptor (ER) levels higher than in the mammary lobule, an evaluation of the effect of this drug on the proliferative activity of both the epithelium and the stroma of fibroadenomas in premenopausal women following the administration of 10 or 20 mg/day over 22 days was proposed. Forty women with fibroadenoma were selected for a randomized double-blind trial. They had regular menstrual cycles and had received neither hormones nor become pregnant 12 months prior to this study. Patients were divided into three groups: A (n = 14; placebo), B (n = 13; tamoxifen 10 mg/day), and C (n = 13; tamoxifen 20 mg/day). The treatment was initiated on the first day of their menstrual cycle and the surgeries were performed on the 22nd day. Estradiol, progesterone, and steroid hormone binding globulin (SHBG) were measured twice. The first measurement was performed on the 22nd day of the previous menstrual cycle and the second one was performed on the day of surgery. The fibroadenoma was fixed in 10% formaldehyde solution and stained with hematoxylin and eosin and then processed through immunohistochemical reaction (PC-10, DAKO code number M879, Denmark A/S). The immunoexpression of the proliferative cell nuclear antigen (PCNA) of at least 500 epithelial and 500 stromal cells was evaluated. Such cells were interactively counted using the Kontron Imaging System KS-300 computerized analysis system, with x 400 magnification. As to PCNA expression in the fibroadenomas' epithelium, the average percentage of stained nuclei in groups A, B, and C was 25.2, 19.3, and 18.0, respectively. However, no significant difference was found in the variance analysis of these data (p = 0.168). As to the study of the fibroadenomas' stroma, the average percentage of stained nuclei found in groups A, B, and C was 32.4, 23.2, and 18.4, respectively. The variance analysis (p = 0.031) and Fisher's multiple comparison test (1.39; 26.67 confidence interval [CI]) confirmed that the number of PCNA-expressing nuclei in the stroma was significantly lower in group C (20 mg/day) compared to group A (control). However, there was no significant difference between group B (10 mg/day) and group C (20 mg/day). It was found that tamoxifen reduced the expression of PCNA in the epithelium and the stroma of the fibroadenoma. However, the effect was only statistically significant in the stroma when a 20 mg/day dose was administered.

Background: Fibroadenomas are the most frequent benign breast neoplasias. Although they are hormone-dependent, no hormonal treatment of proven effectiveness is available for these neoplasias. The objective of the present study was to evaluate the ultrasonographic volume of fibroadenomas in premenopausal women treated with tamoxifen at the doses of 5, 10, 20 mg/day or with placebo for 50 days, starting on the 1st day of the menstrual cycle., Methods: A prospective and randomized study was conducted on 62 eumenorrheic women aged 15 to 45 years with no hormonal treatment or pregnancy during the last 12 months, with a clinical, cytologic and ultrasonographic diagnosis of fibroadenoma, later followed by a biopsy diagnosis. The patients were divided at random into 4 groups: A (n=15; placebo), B (n= 16; 5 mg/day tamoxifen), C (n=16; 10 mg/day tamoxifen), and D (n=15; 20 mg/day tamoxifen). Fibroadenoma volume was measured by ultrasound at 3 different times: on the 22nd day of the cycle that preceded the beginning of tamoxifen treatment, after 1 month of treatment, and on the day of the biopsy (50th day). The mean volume obtained for groups A, B, C and D was 3, 3.3, 1.9, and 2.3 cm3, respecti-vely., Results: Statistical analysis revealed a significant reduction in nodule size only in group D (p=0.0024)., Conclusions: We conclude that tamoxifen significantly reduced fibroadenoma volume when administered for 50 days at the dose of 20 mg/day. Further clinical studies are needed using the drug for a longer period of time, and in order to exclude the need for unnecessary treatment in some women.

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.

Context: The malignant variety of the phyllodes tumor is rare. The occurrence of invasive lobular carcinoma within fibroadenoma is rare as well., Design: Case report., Case Report: A 58-year-old black female patient was referred to the Mastology unit of the Department of Gynecology, Federal University of São Paulo / Escola Paulista de Medicina, in February 1990, presenting an ulcerated tumor in the right breast with fast growth over the preceding six months. She was a virgin, with meno-pause at the age of 45 years and had not undergone hormone replacement treatment. The physical examination showed, in her right breast, an ulcerated tumor of 20 x 30 cm which was not adher-ent to the muscle level, multilobular and with fibroelastic consistency. The axillary lymph nodes were not palpable. The left breast showed a 2 x 3 cm painless, movable nodule, with well-defined edges, and fibroelastic consistency. We performed left-breast mammography, which showed several nodules with well-defined edges, the largest being 2 x 3 cm and exhibiting rough calcification and grouped microcalcifications within it. The patient underwent a frozen biopsy that showed a malignant variant of the phyllodes tumor in the right breast and fibroadenoma in the left one. After that, we performed a total mastectomy in the right breast and an excision biopsy in the left one. Paraffin study confirmed the frozen biopsy result from the right breast, yet we observed that in the interior of the fibroadenoma that was removed on the left, there was a focal area of invasive lobular carcinoma measuring 0.4 cm. The patient then underwent a modi-fied radical mastectomy with total axillary lymphadenectomy. None of the 21 dissected lymph nodes showed evidence of metastasis. In the follow-up, the patient evolved asymptomatically and with normal physical and laboratory examination results up to July 1997.

Objectives: To investigate the proliferative activity of the mammary gland epithelium and plasma levels of progesterone, estradiol, prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and sex hormone-binding globulin (SHBG) in premenopausal women treated with 10 and 20 mg of tamoxifen (TAM) for 22 days., Patients and Methods: A randomized double-blind study was performed with 43 premenopausal women with a diagnosis of fibroadenoma of the breast. The patients were divided into three groups: A (n = 15, placebo); B (n = 15, TAM 10 mg/day) and C (n = 13, TAM 20 mg/day). They started taking an oral dose of TAM or placebo on the very first day of the menstrual cycle. Lumpectomy was performed on the 22nd day of therapy. Normal breast tissue samples were collected during surgery, immediately immersed in 10% buffered formalin, processed for routine histology and immunohistochemistry for proliferating cell nuclear antigen (PCNA) detection. Two peripheral blood samples were collected, both on the 22nd day of the menstrual cycle, in order to evaluate the hormone levels. PCNA expressing epithelial cells were quantified by using a digital program Kontron Image System KS-300 in 1000 cells (400 x )., Results: The percentage of cells expressing PCNA was significantly higher in the group receiving placebo (group A, 50.3%) when compared to groups receiving TAM 10 or 20 mg/day (group B, 24.1%; and group C, 23.2%, respectively) (P < 0.001). Differences between groups B and C were not significant. Levels of progesterone, estradiol and SHBG were significantly higher in B and C groups compared to group A. Increasing concentrations of FSH (P < 0.0045) and lower levels of prolactin (P < 0.0055) were only found in the group receiving 20 mg/day of TAM (group C)., Conclusions: A 22-day TAM therapy, either with 10 or 20 mg/day, significantly reduced the PCNA expression and therefore the proliferative activity of the normal human breast tissue. Increasing levels of estradiol, progesterone and SHBG were associated with TAM therapy at 10 or 20 mg/day. However, a significant change of the level of FSH and prolactin was reached only with a 20-mg/day dose.

The authors investigate the differences between the angiogenesis that occurs in malignant and benign breast tumours (10 specimens of invasive ductal carcinoma and 10 specimens of fibroadenoma) as well as in the adjacent breast stroma of these women highlighting the microvessels by staining their endothelial cells for factor VIII immunohistochemically. The number of vessels counted in invasive ductal carcinoma was significantly higher than the number of vessels counted in fibroadenoma and in the adjacent breast stroma. There was no difference between the number of vessels counted in the fibroadenoma and its adjacent stroma. Even though the patients with invasive ductal carcinoma showed a adjacent stroma with a higher number of vessels, the difference was not significant when compared with the adjacent stroma obtained from patients with fibroadenoma.