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Western blotting and enzymatic activity analysis of cathepsin D in breast tissue and sera of patients with breast cancer and benign breast disease and of normal controls.

Increased total antigen amounts of cathepsin D in breast tissue have been reported to be associated with increased disease recurrence, more frequent metastasis, and increased mortality in breast cancer patients. In the present study, Western blotting analysis has been used for the first time to determine the relative amounts of precursor and processed forms of cathepsin D in sera and breast tissue of patients with breast cancer, benign breast disease, and normal controls. Sera gave similar blots for breast cancer patients and controls with two major forms of cathepsin D (M(r) 52,000 and 27,000). Malignant breast tissue contained the two forms of cathepsin D found in sera and an additional M(r) 31,000 form which was found in significantly increased (P < 0.001) relative amounts in breast tissue from 43 breast cancer patients [24 +/- 12% (SD)] when compared to 51 benign breast disease patients (13 +/- 8.9%) and 23 normal controls (1.8 +/- 4.4%). Preliminary analysis of subgroups of benign breast disease patients suggested no significant difference (P = 0.41) in relative amounts of the M(r) 31,000 form of cathepsin D between proliferative-type and non-proliferative-type fibrocystic breast disease. A cathepsin D assay has been optimized for human breast tissue and used to demonstrate for the first time significantly increased (P < 0.001) amounts of pepstatin-inhibitable, cathepsin D-specific activity in breast tissue from 36 breast cancer patients (2.2 +/- 1.4 units/mg of protein) when compared to 47 benign breast disease patients (0.63 +/- 0.43) and 23 normal controls (0.24 +/- 0.21). Preliminary analysis of subgroups of benign breast disease patients suggested no significant difference (P = 0.21) in pepstatin-inhibitable, cathepsin D-specific activity between proliferative-type and nonproliferative-type fibrocystic breast disease. The positive correlation (r = 0.82) of increased amounts of the M(r) 31,000 form of cathepsin D and increased pepstatin-inhibitable, cathepsin D enzymatic activity in malignant breast tissue suggests that the M(r) 31,000 form is the proteolytically active form of the enzyme which may be involved in the development and/or metastatic spread of breast cancer.

Adult↗

Proteases in cyst fluid from human gross cyst breast disease.

Cyst fluid from women with gross cystic breast disease was found to contain protease activity when assayed against [14C]albumin. At least six different proteases were detected when the fluid was fractionated by a combination of S-300 Sephacel, hydroxylapatite, and DEAE-Sephacel chromatographic techniques. The distribution of the proteases appeared to be related to the ionic composition of the fluids. A major protease component, found in both high Na and high K fluids, was isolated. It showed chymotryptic cleavage characteristics against the beta-chain of insulin. It was partially inhibited by alpha 2-macroglobulin, N-tosyl-L-phenylalanine chloromethyl ketone, and benzamidine but not by leupeptin, pepstatin, N-tosyl-L-lysine chloromethyl ketone, or alpha 1-protease inhibitor. The protease has an apparent molecular weight of 110,000 with Mr 24,000 subunits. This protease may be identical or closely associated with Haagensen's GCDFP-24 progesterone binding protein which was isolated in a similar manner. An imbalance between protease and protease inhibitors in cyst fluid may account for gross cyst formation and may be involved in the tumorigenic process. The accumulation of poorly diffusible peptide fragments, as a result of protease activity, would increase the oncotic pressure leading to enlargement of the cyst cavity as water enters to reestablish osmotic equilibrium.

Female↗

[Inadequate corpus luteum function in benign breast-diseases (author's transl)].

The amount of progesterone and estradiol secreted by human corpus luteum depends upon an adequate release of FSH and LH by pituitary gland during follicular phase and ovulation. In this paper, plasma determination of progesterone and estradiol were carried out in 109 women with benign breast disease during the luteal phase of their menstrual cycle. Results obtained were compared with those observed in 25 normal women studied in the same conditions. In women with benign breast disease, the curve of daily progesterone concentrations during luteal phase was lower than that of normal women. The progesterone peak at 5th day of luteal phase was only 8,1 +/- 3.8 ng/ml instead of 17.2 +/- 3.5 ng/ml in normal women. No significative difference was observed concerning plasma estradiol between patients and normal women. These results indicate that women with benign breast disease have an inadequate corpus luteum function which may be the result of disorder of ovulation. Pathophysiological implications resulting from this observation are discussed.

Breast Diseases↗

Microcalcifications in benign breast diseases. A histological and histochemical study.

A hundred cases of fibroadenomas and 300 cases of benign breast diseases were studied without previous roentgenographic examination of the specimens. Microcalcifications were found in 19% of the fibroadenomas, in 26% of the cases of "fibrous disease" and in 57% of the cases of fibrocystic disease. Benign microcalcifications were not found in normal mammary tissue. They were steadily associated with metaplastic epithelial cells and with their abnormal secretions. Two basic types of microcalcifications were encountered: The granular microcalcifications with a predominately intracellular location and the homogeneous (with or without concentric rings) mainly associated with secreted materials. Microcalcifications were associated with metaplastic epithelial cells of the small eosinophilic variety and with their secretions, with the foam cells and with materials secreted by the apocrine cells. A common histochemical feature in cells or matrixes containing microcalcifications was the presence of compound lipids. The possible relationship of benign breast microcalcifications to the calcifications of other tissues, in connection with their association with lipids is discussed.

Adenofibroma↗

Thermobiological assessment of benign and malignant breast diseases.

The recent technical and clinical advances in breast thermography are reviewed in this article. Emphasis is placed upon liquid crystal thermal imaging and computer-assisted analysis of breast thermograms. New data are presented concerning the value of thermography for the early detection of mammary carcinomas, the identification of women at high risk of developing breast cancer, and the detection of cancer in fibrocystic breasts.

Adult↗

[The study of ultrasonographic diagnosis on breast diseases].

15 sonomammographic findings of 341 histologically proved breast masses were reviewed to improve and objectify the current diagnostic criteria of sonomammography. The author proposed the renewed plan of the diagnostic criteria and the judgement method of benign or malignant breast masses on an electronic linear scanner, offering the author's original diagnostic concept particularly about the shape and the internal echo. This diagnostic approach demonstrated a sensitivity of 93.2%, specificity of 85.9%, and accuracy of 89.7%, which sufficiently showed to raise differential diagnostic capability for breast masses.

Breast Diseases↗

Danazol treatment of severely symptomatic fibrocystic breast disease and long-term follow-up--the Hjørring project.

The purpose of the investigation was to study various aspects of danazol treatment in patients with fibrocystic breast disease and pronounced mastodynia. To qualify for inclusion, the patients in this study had to have a mammographically confirmed prominent glandular structure and/or severe cystic breast disease, associated with pronounced cyclical mastodynia lasting at least one week per menstrual cycle for more than 6 months. They also had to be premenopausal and not undergoing hormonal therapy. Of 109 patients with a mean age of 40 +/- 6.2 (SD) years, who completed 6 months' treatment with danazol, 65% had a pre-treatment history of more than 5 years. According to detailed mammographic characterization, only 18% of the patients had no visible cysts. Of the 82% with visible cysts, half presented with both small (less than 1 cm) and large cysts. The patients were treated in two consecutive groups, 55 patients receiving 400 mg a day and 54 patients 200 mg a day. The therapeutic response was similar following both dosages. Mastodynia responded rapidly and total elimination was noted in about 90% of cases. A marked decrease in prominence of palpable structure was observed in virtually all patients. Mammographically, a decrease in the amount of glandular tissue was observed. These changes during treatment were statistically highly significant (p less than 0.001), irrespective of dose or category of patient. Non-cystic nodularities gradually decreased in 85% and resolved completely in 58% of the cases, but the degree of resolution in the groups of patients with no or only small (less than 1 cm) visible cysts was significantly greater (p less than 0.02 or less) than in the group which also had large cysts and which included the most severe and intractable cases. The mammographical visualization of cysts, ductal system, and fibrous tissue increased initially due to the marked regression of obscuring glandular tissue. Thereafter, a decrease in the number and spread of small cysts was observed in a significant proportion of patients and in some cases a reduction in duct diameter could be demonstrated by means of galactography. Nipple discharge also decreased. The extent of fibrosis appeared to be unaffected by therapy. In the 46 patients with large cysts and, in most cases, a documented history of repeated cyst formation, danazol treatment was found to arrest the development of new cysts and to prevent recurrence for a considerable time thereafter.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Endocrinological aspects of benign breast disease.

The search for an hormonal abnormality as a key determinant of risk of benign breast disease has proved to be as fruitless as that for breast cancer. In both conditions, the initial lesion is likely not to be mediated by the endocrine system. Once normal epithelial cells have been diverted to either a benign or malignant pathway, variations within the normal hormonal range may be sufficient to account for the clinical and biological manifestations of both conditions.

Animals↗

Chlororganic pesticides and polychlorinated biphenyls in breast tissue of women with benign and malignant breast disease.

Persistent chlorinated hydrocarbons assimilated through the diet may, as a result of their carcinogenic, immunotoxic, and, at least in regard to certain of these substances, estrogenic properties, play a role in the etiology of human breast cancer. As a consequence, increased concentrations of these ubiquitous environmental contaminants may be found in breast tissue of women suffering from malignant breast disease. To examine this possibility, surgically removed breast tissue samples from 65 women in Hesse, Germany were examined by capillary gas chromatography for p, p'-dichloro(diphenyl)trichloroethane (p,p'-DDT), p, p'-dichloro(diphenyl)-dichloroethane (p,p'-DDD), p, p'-dichloro(diphenyl)dichloroethene (p,p'-DDE), hexachlorobenzine (HCB), alpha-, beta-, and gamma-hexachlorocyclohexane (HCH) as well as the polychlorinated biphenyls (PCB) no. 28, 31, 49, 52, 101, 105, 118, 138, 153, 156, 170, and 180. Of the 65 patients, 45 were diagnosed with breast cancer. The control group of 20 women suffered from benign breast disease such as mastopathy. After statistical adjustment for age differences, higher concentrations of p,p'-DDT, p, p'-DDE, HCB as well as PCB-congeners no. 118, 138, 153, and 180 were detected in tissue from women with breast cancer than in tissue from control persons. These differences were weakly significant for p, p'-DDE (p = 0.017), for PCB 118 (p = 0.042) and for PCB no. 153 barely not significant (p = 0.083). On an average, a 62% higher concentration of p,p'-DDE was found in cancer tissue (cancer patients: 805 microg/kg fat; controls: 496 microg/kg fat) and 25% higher concentration of PCB no. 118 (81 microg/kg fat; 65 microg/kg fat). The concentrations of beta-HCH, PCB no. 156 and 170 were lower (not significant) in cancer tissue than in tissue from women with benign disease. PCB-congeners no. 105 and 149 as well as gamma-HCH could only be detected in individual tissue samples; congeners no. 28, 31, 49, 52, and 101 as well as alpha-HCH and p,p'-DDD were not detected in any of the samples. To rule out the possibility that the concentrations of chlorinated hydrocarbons measured were influenced by the surgical procedure, 20 samples of tissue that were at a distance (minimum 1 cm and maximum 3 cm) from the tumor, tissue that was in direct proximity to the tumor (no more than 5 mm from the tumor), and tumor tissue itself (center of tumor) were separately prepared and analyzed. The average concentrations of chlorinated hydrocarbons varied to differing degrees and only minimally in tumor and surrounding breast tissue, indicating that the surgical procedure did not influence the results.

Adult↗

Aromatase activity in breast adipose tissue from women with benign and malignant breast diseases.

In order to determine the significance of local oestrogen biosynthesis within the breast, aromatase activity has been measured in adipose tissue from the breasts of women with either benign (n = 36) or malignant breast disease (n = 51). Particulate fractions from all samples possessed aromatase activity, but levels in adipose tissue adjacent to malignant tumours were significantly higher than those in tissue close to benign breast lesions (P less than 0.0001). Elevated aromatase activity in adipose tissue from breast cancer patients may be of importance in view of the central role played by oestrogen in the natural history of breast cancer.

Adipose Tissue↗

The cytopathology of proliferative breast disease. Comparison with features of ductal carcinoma in situ.

Epithelial hyperplasia, a component of proliferative breast disease (PBD), is a known risk factor for the development of breast carcinoma. To determine if criteria established for tissue biopsy could be used to more precisely define cytologic criteria for diagnosis of PBD, 37 breast fine-needle aspirates with biopsy diagnoses of PBD were studied. In cases with adequate cellularity, the following findings were consistently observed: (1) three-dimensional cell clusters with outlying myoepithelial cells, swirling intralumenal masses and peripheral, slit-like, irregular sublumens (65% of cases); (2) convoluted sheets of ductal epithelium with outlying myoepithelial cells and bulbous projections tethered to the ductal lining (29%); and (3) a background of discohesive small frayed groups of ductal cells (32%). Of the 15 cases that did not meet these criteria, most were paucicellular (87%), which suggested sampling error. Other cytologic features that were observed included: moderately increased cellularity (20 cases), moderate-to-marked nuclear overlap (14 cases), minimal nuclear atypia, and few single epithelial cells. Fifteen cases of confirmed ductal carcinoma in situ were studied for comparison. In these cases, cellularity, nuclear overlap, and atypia were increased, but swirling intralumenal masses, prominent myoepithelial cells and slit-like lumens were absent. In conclusion, the features of PBD established for tissue biopsy can be applied to cytologic specimens, and may provide useful clues to the diagnosis of epithelial hyperplasia in breast fine-needle aspiration specimens.

Adult↗

[Application of endoscopy-assistant operation in surgical treatment of breast diseases].

OBJECTIVE: To explore the technique and problems of endoscope-assistant breast surgery. METHODS: Five patients with breast cancer underwent endoscope-assistant modified radical mastectomy, 30 patients with breast cancer underwent endoscope-assistant modified radical mastectomy with small incision, and 13 patients with breast cancer underwent endoscope-assistant resection of breast cancer with retained breast plus axillary lymph node dissection. Two patients with fibroadenoma and 2 patients with fibrocystic disease breast with atypical hyperplasia were treated with endoscope-assistant subcutaneous total mastectomy and breast reconstruction by one-stage silica gel filling operation. Seven patients with fibrocystic disease with atypical hyperplasia and 16 patients with gynecomastia were treated with endoscope-assistant subcutaneous total mastectomy. One 10-month-old infant with huge chest lymphangioma was treated with endoscope-assistant tumor resection via axilla. RESULTS: All operations were performed smoothly. The duration of operation was 180 approximately 360 min. The frozen sections of skin and breast tissue at the incision margin resected during operation endoscope-assistant modified radical mastectomy with small incision and endoscope-assistant conservative surgery were all negative There were 2 cases of postoperative incisional bleeding, 1 case of skin margin necrosis of axillary incision, 1 case of skin margin incisional necrosis after endoscope-assistant resection of breast cancer with retained breast plus axillary lymph node dissection, 4 cases of epidermal necrosis of nipple, and one case of full thickness skin necrosis of nipple surface. CONCLUSION: Endoscope-assistant breast surgery has changed the routine method in breast operation and manifests the cosmetic effects that cannot be achieved by routine surgery.

Adolescent↗

Benign breast disease: the relationship between its histological features and risk factors for breast cancer.

Associations between histologically defined proliferative, but benign, epithelial disorders of the breast and risk factors for breast carcinoma were examined in 568 patients whose breast biopsies were submitted consecutively to the laboratory. Some disorders were associated with multiparity. Blunt duct adenosis was associated with a family history of breast cancer. Apart from a positive association with fibroadenoma, use of oral contraceptives was not associated with any proliferative lesion. Proliferative epithelial lesion changes were not associated with other aspects of obstetric or gynecological history.

Adult↗

[Evaluation and therapy of benign breast diseases].

The majority of women consulting a doctor because of breast symptoms, suffer of a benign breast disease. The variety of benign alterations and diseases may be troublesome. But the fact that the breast or parts of it can show all the alterations known from general pathology makes diagnosis easier. The breast symptom determines the diagnostic method to be used, but clinical examination remains the most important diagnostic tool. The most frequent symptom mentioned by patients is mastalgia. Especially in these cases, the doctor is challenged as diagnostician and as therapist.

Abscess↗

[Role of diaphanoscopy in breast diseases].

The diagnostic value of diaphanoscopy in a series of 200 cases of breast diseases, all confirmed by cytohistologic examination, is illustrated. Diaphanoscopy showed a high sensitivity towards haemorrhagic cysts, early age fibroadenomas, adenosic dysplasia, haematomas as well as carcinomas.

Adult↗

Determination of growth fractions in benign breast disease (BBD) with monoclonal antibody Ki-67.

Certain types of benign breast disease (BBD) carry an increased risk of malignancy. Several morphological criteria such as an atypia score are used to define this group, and the use of a kinetic parameter may provide additional information. Therefore, the growth fractions of 120 benign breast lesions were determined using the monoclonal antibody Ki-67. The values obtained range from 0.3% to 10.8% (average 3.1% +/- 2.2%) compared to breast carcinomas with an average of 15.3% +/- 10.1%, range 0.8% to 47.8%. All specimens were classified using the terminology of Azzopardi. The prevailing histological entities were cystic disease, fibroadenoma, and blunt duct adenosis. Between these groups no differences in growth fractions were observed. Postmenopausal patients had slightly lower values than premenopausal women. Further prospective studies are needed to evaluate whether those cases of BBD with a high number of Ki-67 positive cells have an increased risk of breast cancer, independently from conventional histological classifications.

Adenoma↗