Controversies in benign breast disease

Breast health means more than breast cancer. At least 50% of patients seen at a multidisciplinary breast center have benign conditions. Pain, nipple discharge, and a question of a mass are the usual chief complaints. This article provides contemporary information and management guidelines for the common breast conditions associated with these complaints.     

p53 protein expression in benign and malignant breast lesions

OBJECTIVE: To investigate p53 protein expression in imprints from benign and ductal breast carcinoma cases in relation to the histologic grade of malignancy and clinical stage. STUDY DESIGN: The study group consisted of 60 cases of primary ductal breast carcinomas and 20 benign lesions. For the demonstration of p53 protein expression, an immunocytochemical avidin-extravidin complex technique was applied. Monoclonal antibody p53 was used as the primary antibody, diaminobenzidine as the chromogen and hematoxylin as the counterstain. RESULTS: Forty-five percent of breast cancer cases showed positive expression of p53. A statistically significant difference in p53 protein expression was observed between grade 1, 2 and 3 carcinomas and stage I, II and III cases. All benign lesions were negative for p53 protein expression. CONCLUSION: Immunocytochemical p53 protein expression in cytologic material is a simple method that can be applied in routine cytologic laboratories for the identification of genetic alterations in primary ductal breast cancer.     

Telomerase activity in benign proliferative breast disease and breast cancer

The application of telomerase activity is expected to serve as a reliable indicator of biological malignancy in breast tumors. We performed a study to quantify telomerase activity, the results of which revealed that this activity tends to be unexpectedly low in scirrhous carcinoma having low histological differentiation. It is therefore felt that additional studies at the tissue level using in situ hybridization will be required in the future. Although we think that atypical cystic duct is a true pre-cancerous lesion in the sense of having a high possibility of progressing into breast cancer, it will be interesting to determine whether or not the tissue is composed of cells having telomerase activity.     

Danazol for benign breast disease

Three groups of women with benign breast disease were treated with danazol for 3 to 6 months. Doses of 100 mg per day were given to 40 patients, 200 mg to 55, and 400 mg to 35. The age range of the patients was 20 to 48 years. The patients were rechecked at 6-month intervals over a period of 48 months. Most of them were seen four or more times after completion of therapy. Elimination of nodularity occurred in about two thirds; three experienced no improvement, and partial resolution was obtained in the remainder. Untoward effects were minimal or trivial. Danazol proved to be an excellent hormonal agent in the management of fibrocystic disease of the breast.     

Epidemiologic characteristics of benign breast disease

To see if the risk factors associated with fibroadenoma and cystic disease were similar to those reported for breast cancer, a retrospective study of benign breast tumor in a general population was conducted in Washington County, Maryland. The study population consisted of 320 white women 20 to 49 years of age who had had benign breast disease and 320 age-matched controls. More cystic disease cases than controls had the following characteristics, which had been reported to have been associated with breast cancer in other studies: higher socioeconomic status; fewer pregnancies; and a lack of association with lactation patterns. Nulliparity, late natural menopause and a maternal history of breast cancer were also more common among cystic cases than controls, although these differences could have occurred by chance. Cystic disease cases and controls did not differ with respect to other factors associated with breast cancer, such as early age at menarche, late age at first pregnancy, and negative history of artificial menopause. In contrast to cystic breast disease, fibroadenoma was not associated with most of the risk factors of breast cancer.     

Computer-derived nuclear features distinguish malignant from benign breast cytology

This article describes the use of computer-based analytical techniques to define nuclear size, shape, and texture features. These features are then used to distinguish between benign and malignant breast cytology. The benign and malignant cell samples used in this study were obtained by fine needle aspiration (FNA) from a consecutive series of 569 patients: 212 with cancer and 357 with fibrocystic breast masses. Regions of FNA preparations to be analyzed were converted by a video camera to computer files that were displayed on a computer monitor. Nuclei to be analyzed were roughly outlined by an operator using a mouse. Next, the computer generated a "snake" that precisely enclosed each designated nucleus. The computer calculated 10 features for each nucleus. The ability to correctly classify samples as benign or malignant on the basis of these features was determined by inductive machine learning and logistic regression. Cross-validation was used to test the validity of the predicted diagnosis. The logistic regression cross validated classification accuracy was 96.2% and the inductive machine learning cross-validated classification accuracy was 97.5%. Our computerized system provides a probability that a sample is malignant. Should this probability fall between 30% and 70%, the sample is considered "suspicious," in the same way a visually graded FNA may be termed suspicious. All of the 128 consecutive cases obtained since the introduction of this system were correctly diagnosed, but nine benign aspirates fell into the suspicious category.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fatty acid composition of breast adipose tissue in breast cancer patients and in patients with benign breast disease

In this study, we report on the cell adhesion properties of marrow stromal cells to extracellular matrix components such as collagen and noncollagenous proteins. The osteoblastic cells and their non-osteoblastic counter-parts (MBA series) from the marrow stroma differentially recognized a spectrum of extracellular matrix proteins. The osteoblastic cells, MBA-15, preferentially attached to bone matrix proteins, whereas fibroendothelial MBA-2.1 and adipocytic 14F1.1 cells did not. The MBA-15 cells demonstrated a preference in their attachment to fibronectin > mixture of collagens > bone matrix extracts > collagen type I > noncollagenous proteins. Clonal subpopulations derived from the MBA-15 cell line representing various stages along the osteogenic lineage expressed differential attachment preference. MBA-15.4, a less differentiated clonal line, was compared to MBA-15.6, a mature cell line.     

False-positive postmortem EMIT drugs-of-abuse assay due to lactate dehydrogenase and lactate in urine

Three cases of multiple false-positive drug tests are described. Postmortem urine specimens were screened using the enzyme-multiplied immunoassay technique. All patients had proteinuria and lactic aciduria. These false-positive reactions were due to the presence of lactate dehydrogenase (LDH), lactic acid, and protein. This finding was confirmed by creating a multiple false-positive sample with a solution of LDH and lactate in 5% bovine serum albumin at pH 6.     

Immunohistochemical detection of c-erbB-2 and p53 in benign breast disease and breast cancer risk

BACKGROUND: We studied the associations between c-erbB-2 protein overexpression and p53 protein accumulation in benign breast tissue and the risk of subsequent breast cancer. METHODS: We conducted a case-control study nested within the cohort of 4888 women in the National Breast Screening Study (NBSS) who were diagnosed with benign breast disease during active follow-up. Case subjects were the women who subsequently developed breast cancer (ductal carcinoma in situ [DCIS] or invasive carcinoma). Control subjects were matched to each case subject on NBSS study arm, screening center, year of birth, and age at diagnosis of benign breast disease. Histologic sections of benign and cancerous breast tissues were analyzed immunohistochemically. Information on potential confounding factors was obtained by use of a self-administered lifestyle questionnaire. RESULTS: Accumulation of p53 protein was associated with an increased risk of progression to breast cancer (adjusted odds ratio [OR] = 2.55; 95% confidence interval [CI] = 1.01-6.40), whereas c-erbB-2 protein overexpression was not (adjusted OR = 0.65; 95% CI = 0.27-1.53). The findings for c-erbB-2 and p53 did not differ among strata defined by menopausal status, allocation within the NBSS, history of breast disease, and whether the benign breast disease was detected at a scheduled screen or between screens. The results were also similar after exclusion of case subjects whose diagnosis of breast cancer occurred within 1 year of their diagnosis of benign breast disease and after exclusion of subjects with DCIS. CONCLUSIONS: p53 protein accumulation, but not c-erbB-2 protein overexpression, appears to be associated with an increased risk of progression to breast cancer in women with benign breast disease.     

Clinical applications of lactate dehydrogenase isoenzymes

A quantitative electrophoretic test for the determination of lactate dehydrogenase isoenzymes was applied to the analysis of human tissues, cells and fluids in order to obtain their normal isoenzyme patterns and to form a reference record. The same test was employed in the analysis of serum samples from patients with defined pathological conditions. The abnormal serum isoenzyme patterns were correlated with the tissue patterns, thus indicating the origin of the abnormality. This type of correlation, together with the clear demonstration of the actual isoenzymes and their quantitation, improves diagnostic discrimination and enhances the early detection of a biochemical abnormality that aids in the prevention of disease.     

Thromboelastographic distinction of malignant from benign breast masses: a preliminary report

Thromboelastography is a newly applied tool for the detection of carcinoma. By comparing the thromboelastograph (TEG) of fresh whole blood (native) to that of blood to which celite has been added (celite activated), enhanced clotting is manifested which allows identification of individuals harboring carcinoma. Twenty women, obtained in a random sampling, entering the North Carolina Baptist Hospital for biopsy of breast masses were studied with routine clotting tests and TEGs preoperatively. TEG prediction of the biopsy result was correct in 16 of 20 patients (P less than 0.05). Thromboelastography may be a useful adjunct in screening for carcinoma in the evaluating persons with masses of unknown histology.     

Serum lactate dehydrogenase isoenzyme pattern in neuroblastoma

Total serum LDH activity and isoenzyme distribution were studied in children with neuroblastoma at the time of hospital admission. The total LDH was determined in 26 cases, and 20 (77%) of them showed elevation of its activity. On the other hand, in 9 of these 26 cases, the isoenzyme distribution was determined along with the total LDH. All 9 cases, 4 of them with normal total LDH activity, showed an abnormal isoenzyme pattern with a percentage increase in the intermediate fractions (malignant pattern). The results suggest the usefulness of the determination of serum LDH isoenzymes as a screening procedure in children with malignant tumors including neuroblastoma.     

Immunoglobulin content in the bronchial washings of patients with benign and malignant pulmonary disease

The bronchial washings of 58 patients with benign and neoplastic conditions involving the lungs were evaluated for immunoglobulin content. Levels in the washings from the diseased lung were compared with those from the normal contralateral lung. In normal patients and those with either bilateral inflammatory diseases or unilateral bronchiectasis or tuberculosis, the mean variation in igA/K and igG/K ratios between diseased and uninvolved lungs was minimal. In unilateral pneumonitis, however, igG/K was markedly elevated (P less than 0.01). Significant changes in the igA/K occurred on the affected side in patients with cancer. In the group with squamous-cell cancer. the mean elevation was 4.6 times that of contralateral lung (P less than 0.005), whereas with adenocarcinoma and undifferentiated carcinoma, the rise was 6.4 and 2.8 times, respecitvely (P less than 0.01 and P less than 0.01). Thus, carcinoma appears to alter local immunoglobulin production in the affected lung as compared to its normal counterpart. (N Engl J Med 295:694-698, 1976).