Cases Of Benign Breast Disease Research Articles

Insulin-like growth factor 1 receptors (IGF1-R) and IGF1 in human breast tumors

To appreciate the IGF1 sensitivity of breast tumors we detected IGF1-R with a biochemical assay (RRA). We then localized and quantified IGF1-R on frozen tissue sections by histo-autoradiographic analysis (HAA). In some cases, the IGF1 and IGF1-R mRNA expression were studied by Northern blot analysis. We also studied the IGF1 plasma concentration in primary breast cancers compared to controls. IGF1-R (RRA) were found in 87% ( n = 297) of the breast cancers. The mean geometric value was 3.87% (specific binding as percentage of total radioactivity); we found a highly significant correlation between IGF1-R and ER on the one hand ( P = 0.0001) and PgR on the other ( P = 0.0001) (Spearman test). The presence of IGF1-R was associated with a better prognosis, either on relapse-free survival (actuarial analysis: P = 0.004; Cox analysis: P = 0.005) or overall survival (respectively P = 0.003; P = 0.005). The median duration of follow-up was 30 months. By Cox analysis IGF1-R was a better prognostic factor than ER and PgR. In a series of 77 cases of benign breast disease only 47% (36/77) were positive; the mean geometric level was 1.8%. The HAA IGF1-R quantification in 20 breast carcinomas and 12 cases of benign breast disease confirmed the RRA results and demonstrated that the labeling was localized on the epithelial component. In four breast cancers, we did not detect IGF1 mRNA; IGF1-R probe demonstrated two major mRNAs of 11 and 7 kB. Finally we found that IGF1 plasma level was higher in breast cancer patients than in healthy controls of the same age. These results show that IGF1 is implicated in breast cancer growth and suggest that anti-IGF1 treatment might be useful in human breast cancer: for this reason, we and others carried out a phase II clinical trial with somatostatin.

Nutritional factors associated with benign breast disease etiology: a case-control study

Between 1977 and 1980, 854 biopsied cases of benign breast disease (BBD) and 755 matched surgical and 723 matched neighborhood controls subjects were interviewed in Israel by using a detailed food frequency questionnaire. Cases were classified according to degree of ductal atypia (Black-Chablon grading system). Women with atypic lesions (grades greater than or equal to 3) reported a higher intake of all types of foods compared with both control series. Further analyses indicated that the increased consumption was due primarily to foods containing greater than or equal to 10% fat. Odds ratios associated with the highest fat consumption quartile were close to 3.0. There was a trend for increasing saturated fatty acid consumption with increasing ductal atypica. After adjusting for hormonal and demographic confounders, the association with fat intake was strengthened. Because atypic BBD has been reported to be a precursor of breast cancer, our findings lend support to the hypothesis that dietary fat is a risk factor for breast cancer.

Presence and characterization of insulin-like growth factor 1 receptors in human benign breast disease

Insulin-like growth factor 1 binding sites were characterized in human benign breast disease. We demonstrated the presence of one high affinity binding site. Chemical cross-linking of [ 125 I]IGF1 to benign breast disease membranes in reducing condition and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed one band with an apparent M r of 130,000. The specificity of the binding was studied: IGF 2 was a good competitor whereas insulin competed for binding with a potency lower than 1 100 that of IGF 1. This IGF 1 binding corresponded to the previously described type 1 IGF receptor (IGF 1-R). IGF 1-R was assayed in 35 cases of benign breast disease and two samples of normal breast tissue. Forty-three per cent of the lesions were IGF 1-R positive. The mean geometric level of specific binding was 1.98% in the whole population, it was significantly lower in adenofibromas ( 1.55%) than in epithelial hyperplasia ( 2.5%); it was 2% in dystrophic disease. IGF 1-R was undetectable in normal tissue. Considering our previous results showing that almost all the breast cancers contained IGF 1-R, these data suggest that the increase in IGF 1-R could be a marker of malignant tumor development.

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.

Estrogen and progesterone receptors in benign breast tumors and lesions: relationship with histological and cytological features.

The pattern of estrogen (ER) and progesterone receptors (PR) and their relationship to histo- and cyto-pathological parameters has been studied in 97 cases of benign breast disease and benign phyllode tumors (95 women, of whom 76 were premenopausal, and 2 men). Total (cytosolic + nuclear) ER and PR were assayed by a single-saturating dose method using a tris-KCl buffer. The cut-off between positive and negative ER and PR assay was 100 femtomoles/g tissue. All specimens were processed for histological examination: epithelial and fibroblastic proliferation, epithelial/stromal ratio and presence of focal or diffuse hyalinosis. In 33% of the 46 cases of fibrocystic disease one receptor at least was present (13% ER+, 31% PR+). All the 8 cases in which infiltrating epitheliosis was present were PR+ and 4 of them were also ER+. In 72% of the 31 fibroadenomas one receptor at least was present (19% ER+, 71% PR+). In all these cases levels of receptors were lower than in malignant tumors. An inverse correlation between PR + prevalence and fibrohyalinosis was observed; on the other hand a positive relationship between PR + and fibroblastic (p less than 0.001) or epithelial (p less than 0.01) proliferation was found. In all 5 benign phyllode tumors examined PR + were present at a very high level, almost as high as in malignant tumors. Of the 15 other benign breast lesions, all but one (1 hamartoma) were ER- and PR-.

Benign breast lesions with malignant clinical and mammographic presentations

Nine cases of benign breast disease in which mammograms had been false-positive were collected at Northwestern Memorial Hospital. In all but one case the patients had presented initially with questionable masses that required biopsies with requests for frozen section diagnoses. Included in the study were three cases of indurative mastopathy, three cases of fibrocystic disease with sclerosing adenosis, and one case each of sclerosing papillary proliferation, infarcted intraductal papilloma, and fat necrosis with foreign body giant cell reaction. The mammographic and histologic findings for all cases were reviewed. Indurative mastopathy is a poorly known entity with radiologic features highly suggestive of malignancy. As described previously (Cancer 47:561, 1981), the lesion consists of a central nidus of elastosis with irregular projections radiating into the adjacent breast tissue. Peripheral areas of the infarcted papilloma and sclerosing papillary proliferation could be confused with infiltrating carcinoma in frozen sections. Familiarity of pathologists with these lesions is essential for avoiding the overdiagnosis of carcinoma.

A Case-Control Study of Caffeine and Methylxanthines in Benign Breast Disease

A dietary case-control study of 854 histologically diagnosed cases of benign breast disease (BBD), 755 matched surgical controls, and 723 matched neighborhood controls was conducted in Israel between 1977 and 1980. No association between coffee consumption and BBD was found. Analyses by histological type, degree of ductal atypia, age, sex, and ethnic origin, controlling for several confounding factors, confirmed the lack of association. The estimated mean intake of methylxanthines was also similar for cases and controls (302, 312, and 313 mg for cases, surgical controls, and neighborhood controls, respectively). No evidence of a dose-response was noted. Our results suggest that there is no association between coffee or methylxanthine consumption and BBD, although we had a 70% chance of finding a risk ratio of 1.5 with an error of 5%.

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.

The Noncontraceptive Health Benefits from Oral Contraceptive Use

Studies have documented the protective effects of oral contraceptives (OCs) against 5 diseases: 1) OCs prevent 50-75% of potential cases of benign breast disease; there is an estimated annual reduction of 235 hospitalized cases for every 100,000 U.S. women using OCs or about 20,000 hospitalizations each year. 2)OCs reduce the occurrence of retention cysts of the ovary; an estimated 3000 surgical procedures for ovarian cysts are prevented each year in the U.S. 3) OC users have approximately 45% less iron-deficiency anemia than nonusers due to less menstrual flow. 4) OCs protect against the development of pelvic inflammatory disease (PID); 600 of every 100,000 OC users are prevented from contracting a 1st episode of PID and 156 PID hospitalizations are averted for every 100,000 OC users annually. 5) OCs protect against ectopic pregnancy; approximately 120 hospitalizations/100,000 users are prevented annually. 3 additional diseases may be prevented by OCs, although the evidence is not as conclusive as for the 5 previously discussed; OC users are only 1/2 as likely to develop: 1) rheumatoid arthritis, 2) endometrial cancer, and 3) ovarian cancer as nonusers. OCs have also been shown to reduce the incidence of such disorders as excessive menstrual bleeding, irregular menses, intermenstrual bleeding, painful menstruation, and premenstrual tension.

Benign Breast Disease and Oral Contraceptive Use

A random selection of 1,230 upstate New York childbearing women was used to examine the history of oral contraceptive use in women with a clinical diagnosis of benign breast disease. We found that 73 women who had benign breast disease had a reduced duration of pill use. When determining the reason for this reduction, we found that in a significant portion (P less than .05) of our benign breast disease cases, the women had been advised by their physicians to discontinue pill use for breast-related reasons. We then surveyed a large group of upstate New York physicians. One third of them considered benign breast disease a potential contraindication for starting oral contraceptive use. Nearly one half throught the development of benign breast disease to be a potential contraindication for continuing oral contraceptive use. It is premature to conclude that oral contraceptive usage protects against benign breast disease.