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PubMed1999

Serum levels of insulin-like growth factor binding protein-3 in benign and malignant breast disease.

BACKGROUND: The insulin-like growth factors IGF-I and IGF-II and their major binding protein IGFBP-3 influence the growth of breast cancer cells in vitro. Some benign non-breast tumours appear to be associated with increased serum IGFBP-3 levels which would tend to reduce bioactive-free IGF concentrations. The present study investigates whether this pattern also occurs in neoplastic breast disease. METHODS: Serum IGF-I, IGF-II and IGFBP-3 were measured by specific radioassay in 12 women with benign breast disease, 31 patients with breast cancer and in age-matched controls. RESULTS: The mean (+/-SD) serum IGFBP-3 concentration was higher in benign breast disease (3.6+/-0.7 mg/L) than in controls (2.7+/-0.6 mg/L) or in breast cancer patients (2.7+/-0.5 mg/L) (P = 0.001). Serum IGF-I and IGF-II levels were not significantly different among the groups. However, the index of free unbound IGF measured as the molar ratio of IGF-I plus IGF-II divided by IGFBP-3 was significantly lower in benign breast disease than in the other subjects. CONCLUSIONS: Either the production or clearance of IGFBP-3 is altered in benign breast disease so that there is less free IGF available to cells. This may serve to protect against malignant transformation in patients with benign breast disorders.

Adult↗

PubMed1993

Breast disease and the general surgeon. I. Referral of patients with breast problems.

OBJECTIVES: To determine the proportion of all new and follow-up patients referred to general surgical outpatient clinics with breast problems. To ascertain how long these patients wait for an appointment and how many require investigation or admission for operation. To review our management of patients with breast problems in the clinic and to determine the ratio of benign breast disease to malignancy. DESIGN: A 3-month prospective outpatient survey with patient details recorded on questionnaires completed by the medical staff. SETTING: The general surgical outpatient clinics of this firm at Battle Hospital, Reading, and Newbury District Hospital, Berkshire. PATIENTS: Those patients attending the above clinics during the 3-month period 1 October to 31 December 1989. RESULTS: In all, 693 new patients and 554 follow-up patients were seen. Of the new patients, 119, and of the follow-up patients 140 were seen for a breast complaint. At Battle Hospital 16% of all new patients presented with a breast problem, while at Newbury Hospital the figure was 24%. Of the follow-up patients at Battle Hospital, 23% were seen for a breast problem, and 41% at Newbury. The overall median waiting time for a new outpatient appointment was 21 days. No investigations were needed in 22% of the patients. The remaining 93 patients had investigations and a total of 70 mammograms and 53 fine needle aspirations for cytology were performed. The mean cost of investigations per patient investigated was estimated at 27 pounds. Of new patients, 58% were discharged from the clinic after a single consultation, and investigations as necessary. In 79% of the patients admitted for an operation, the decision to admit was made on the basis of the initial history and examination alone. Of new patients, 84% did not need admission and were managed in the clinic. In all, 14 breast carcinomas were diagnosed--12% of new patients with breast problems. CONCLUSIONS: The figures suggest that 24% of new patients and 41% of follow-up patients attending a general surgical clinic are seen for a breast problem. The waiting time for new appointments is unacceptably long. Most new patients do not require admission for an operation. Only 12% of new patients referred with a breast problem were found to have a carcinoma.

Appointments and Schedules↗

PubMed2003

Integrated breast diseases research and cancer registry in Turkey.

A system we call BDRS is implemented as an integrated disease specific system for breast diseases in order to obtain and use patient health data for clinical research, cancer registry and clinical care. It is an open, flexible and modular system that supports multi-institutional and multi-viewed utilization of health data. Three-tier web based architecture, and object oriented technologies have been employed to ensure its extendibility. Exchange and sharing of health data have been implemented with XML.

Biomedical Research↗

PubMed1999

Risk of breast cancer in Japanese women with benign breast disease.

To investigate the risk of breast cancer development in women with benign breast disease (BBD), 387 screen-detected BBD women and 1,489 normal women, taken from participants in the breast cancer screening program during 1978-1986, were followed through 1991. While 2,811 person-years in the BBD group and 11,018 person-years in the normal group were accumulated, 5 women in the BBD group and 6 women in the normal group developed breast cancer. Using the Mantel-Haenszel method, relative risks (RR) were estimated for all women with BBD and women in some BBD types. Significantly elevated risk of breast cancer was observed in all women with BBD (RR = 3.26, 95% confidence interval (CI) 1.08-9.83). Women with proliferative BBD were at high risk of breast cancer (RR = 8.48, 95% CI 2.99-24.10), but no increased risk was observed for women with non-proliferative BBD (RR = 0.93, 95% CI 0.11-7.66). These results are consistent with those in high-risk countries for breast cancer. In the management of women with BBD, histopathological diagnosis of the breast lesion is essential and women with proliferative BBD should be followed up carefully.

Adult↗

PubMed2001

Histological and biological evolution of human premalignant breast disease.

Most human invasive breast cancers (IBCs) appear to develop over long periods of time from certain pre-existing benign lesions. Of the many types of benign lesions in the human breast, only a few appear to have significant premalignant potential. The best characterized of these include atypical hyperplasias and in situ carcinomas and both categories are probably well on along the evolutionary pathway to IBC. Very little is known about earlier premalignant alterations. All types of premalignant breast lesions are relatively common but only a small proportion appear to progress to IBC. They are currently defined by their histological features and their prognosis is imprecisely estimated from indirect epidemiological evidence. Although lesions within specific categories look alike, they must possess underlying biological differences causing some to remain stable and others to progress. Recent studies suggest that they evolve by highly diverse genetic mechanisms and research into these altered pathways may identify specific early defects that can be targeted to prevent premalignant lesions from developing or becoming cancerous. It is far more rational to think that breast cancer can be prevented than cured once it has developed fully. This review discusses histological models of human premalignant breast disease that provide the framework for scientific investigations into the biological alterations behind them and examples of specific biological alterations that appear to be particularly important.

Breast↗

PubMed1975

Diagnostic error in breast disease.

Fifty-six breast biopsies, incorrectly assessed by preoperative clinical or mammographic examination, were reviewed to define the characteristics in the tumor or patient that caused the clinician and mammographer to be diagnostically inaccurate. The most important patient characteristic associated with error was the use of hormones. Failure to recognize that oral contraceptive use significantly reduces the incidience of benign breast disease contributed to the frequent misdiagnosis of lesions in those patients. Twelve of 16 masses in oral contraceptive users were malignant. In seven, their resemblance to cysts or fibroadenomas resulted in treatment delay of two weeks or 18 months. Because benign disease is uncommon in women who have used contraceptives two or more years, all new lesions in those women should be studied by biopsy promptly. Neither clinical nor mammographic evaluation of lesions in postmenopausal women who used estrogens was accurate. Twelve postmenopausal patients with carcinoma had used estrogens. Three of these lesions were considered benign clinically and four, by mammogram. In one, treatment was delayed four years. In women over 50 not using hormones, clinical diagnosis of malignancy was accurate. Ten carcinomas in those women were missed by mammogram. Eight had negative nodes; thus a negative mamogram when the clinical diagnosis is correct may be an effective guide in predicting the status of axillary nodes. Paget's disease was not recognized clinically in two of eight patients with that disease, and an additional two were not recognized on mammography. The initial examiner did not identify three of six inflammatory carcinomas. Ten percent of benign lesions were intraductal hyperplasia or papillomatosis with atypia and were the benign lesions most often misdiagnosed clinically and by mammogram. No microscopic lesions were noted on mammography without an associated palpable mass. Twenty-five per cent of the lesions in women aged 40-49 were incorrectly assessed by mammography or clinical examination. Four (15%) of the 27 carcinomas in this age group were not recognized by either modality. Mammography helped delineate the characteristics of masses in premenopausal women. With recognition that any mass that appears in a woman using oral contraceptives must be studied by biopsy, combined clinical and mammographic study in primenopausal women should minimize diagnostic error. Unfortunately, neither clinical nor mammographic evaluation of the women with irregular periods approaching menopause or within three years past menopause is accurate. It is in that age group that new diagnostic modalities are needed and when reported their efficacy in that age group should be stressed.

Adult↗

PubMed2005

Secretome analysis of microarray data reveals extracellular events associated with proliferative potential in a cell line model of breast disease.

It is widely believed that breast cancer develops in a multistep process with premalignant lesions preceding invasive carcinoma. The characterization of molecular events associated with premalignant progression would improve our understanding of carcinogenesis and greatly benefit the development of early detection methods and chemoprevention strategies. However, the molecular biology of precancerous breast disease is poorly understood. To better characterize extracellular events associated with disease progression, such as cell-cell and cell-extracellular matrix (ECM) signaling, we analyzed gene expression profiles for the set of genes coding for secreted proteins (the secretome) in a cell line model of human proliferative breast disease (PBD). PBD describes a series of preneoplastic changes in the inner lining of milk glands associated with a dramatic increase in the risk of breast cancer. We used a series of cell lines with increasing proliferative propensity, and cell cultures were grown on matrigel to emulate in vivo growth and ECM interactions. Microarray analysis identified two clusters of secretome genes with expression profiles correlating to PBD progression. Some of the identified genes have previously been associated with breast malignancies, and our results suggest that changes in expression for these genes begin in the premalignant stage, offering potential use for early detection and as chemotherapeutic targets. RT-PCR validation demonstrates the reliability of the microarray results.

Breast Neoplasms↗

PubMed1998

Breast development gives insights into breast disease.

AIMS: Studies of developing human breasts are essential for understanding the organogenesis as well as molecular pathogenesis of benign and malignant breast diseases. In this study we have examined the distribution of TGF-alpha, TGF-beta 1, tenascin-C and collagen type IV with the aim of starting to build a picture of the profile of molecules that may be involved in the development of the human breast. METHODS AND RESULTS: Ten fetal breasts (16 to 23 weeks of gestation) and 45 infant breasts, ranging in age from newborn to 2 years, were used in this study. Paraffin sections from these samples were immunostained with antibodies for these proteins and for Ki67 to elucidate the level of proliferative activity in different stages of breast development. TGF-alpha immunoreactivity was observed both in the stromal and the epithelial cells within fetal and infant breasts up to 25 days. TGF-beta 1 immunoreactivity was localized in the extracellular matrix. Tenascin-C was found around the neck of the developing breast bud and in the extracellular matrix of the infant with peaks in the newborn at 6-12 weeks. The immunoreactivity for type IV collagen was more intense in the region of the breast bud neck in the fetal breasts and reduced around the tips of lobular and terminal-end buds within the infant breasts. CONCLUSIONS: The distribution of the growth factors and extracellular matrix proteins within the developing human breast indicates that they play a significant role in different cellular compartments during morphogenesis and provides insights into breast disease.

Breast↗

PubMed1977

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.

Adult↗

PubMed1990

Vitamin E and benign breast disease.

Vitamin E has been used in the treatment of benign breast disease for 25 years. To evaluate the efficacy of treatment by means of mammography as the objective and sensitive parameter, 105 women were randomly selected and entered into a double-blind, placebo-controlled crossover trial. All patients had mammographic evidence of benign breast disease. They received 600 mg of placebo and alpha-tocopherol acetate in 3-month treatment phases. Breast examinations and mammography were done, after each treatment, at approximately the same phase of the patients menstrual cycle. No significant subjective or objective effects after treatment were observed. We conclude that alpha-tocopherol is not beneficial in the treatment of benign breast disease. We would warn against the use of alpha-tocopherol for misdirected treatment of undiagnosed overt disease because such treatment may delay the diagnosis of breast cancer.

Adult↗

PubMed1992

Identification of the major protein components in breast secretions from women with benign and malignant breast diseases.

The protein composition of breast secretions from 99 premenopausal women with benign or malignant breast diseases and from 70 control women without breast pathologies has been studied by using polyacrylamide gel electrophoresis. These fluids have been classified into two types according to their major polypeptide components. Type I fluids are defined by three major distinctive bands at Mr 44,000, 24,000, and 17,000, while those designated Type II present distinctive bands at Mr 80,000, 15,000, and 14,000. Amino acid sequencing and immunoblotting analysis demonstrated that proteins in Type I secretions correspond to Zn-alpha 2-glycoprotein, apolipoprotein D, and gross cystic disease fluid protein-15, while those from Type II fluids have been identified as lactoferrin, lysozyme, and alpha-lactalbumin. Most women (93%) without breast pathology and most patients (88%) with benign diseases had secretions with a Type I polypeptide pattern. By contrast, a large percentage (57%) of secretions from women with breast carcinoma presented a Type II protein pattern. Further studies with a large number of women will be useful for corroborating the potential clinical interest of breast fluid protein analysis.

Adult↗

PubMed1985

[The significance of X-ray diagnosis of breast diseases].

In general, the breasts themselves of Japanese women are small because their breast fatty tissues are not so developed as those of Caucasian women. Therefore, conventional mammogram tends to show a poor contrast of a tumor in the surrounding breast tissues. In order to overcome the poor contrast, we have been taking the picture of compression spot by a special small cone. Our compression spot studies made it possible to show the margin of the tumor shadow more clearly and to reveal the features of minute calcification more precisely. As the results of our experience using these procedures, we believe that the compression spot studies following the conventional mammograms are the most useful diagnostic technique for breast cancers. In addition to describe the clinical significance of the X-ray examination for breast cancers, we also discuss the mammographical differential diagnosis between the cancers and benign lesions mimicking cancers.

Breast Diseases↗

PubMed1985

Risk factors for fibrocystic breast disease and its histopathologic components.

The relationship between various sociodemographic, reproductive, and other factors to the occurrence of fibrocystic breast disease was evaluated in a case-control study undertaken at five Connecticut hospitals from 1979 to 1981. The study groups comprised 590 women with biopsy-proven fibrocystic breast disease and 1,018 women with other surgical conditions. Among the premenopausal women, multivariate analysis suggested that high socioeconomic status, Jewish religion, low parity, a history of benign breast disease, a history of breast cancer in the mother or a sister, and low Quetelet index were associated with increased odds ratios (OR) for fibrocystic breast disease. Similar analysis for the postmenopausal women revealed increased OR for women with high socioeconomic status, a late age at menopause, and a history of benign breast disease. Current smokers as well as those who had had a tubal sterilization had significantly reduced odds of fibrocystic disease. There was no convincing evidence of linear trends according to degree of epithelial atypia for any of the variables considered. Although some variation in the OR emerged in the analysis according to selected histologic components, the results provided little evidence that women with biopsy specimens exhibiting gross cysts, sclerosing adenosis, papillary hyperplasia, or papillomatosis showed epidemiologic similarities with breast cancer patients.

Adult↗

PubMed1983

Evaluation of the LAI test in patients with benign and malignant breast diseases.

Tumor "specific" immune recognition was assayed in 125 patients with various breast diseases including breast cancer of clinical stage I and II, 22 patients with other malignancies and 64 healthy persons employing leukocyte adherence inhibition test (LAI). In the group of breast cancer patients (BC) there were 81% of positive responders (52/65) with a mean nonadherence index (NAI) value 67.4. Sensitization to extract derived from breast cancer was detected in 38.3% (23/60) of patients with benign breast diseases (BBD). The mean NAI value was significantly lower comparing to NAI value of BC patients (34.8 vs. 67.4) but exceeded the upper limit of normal values. The most frequent positive responders of BBD group were found in patients with proliferative mastopathy (11/17). Our study brought further evidence that BC patients and in a lesser degree BBD patients are sensitized to some antigen(s) contained in selected breast tumor extracts. However, high proportion of false positive results in healthy persons (14.1%) and mainly considerable number of positive responders in BBD patients represent a major limitation for clinical diagnostic usefulness of the LAI assay.

Antigens, Neoplasm↗

PubMed1980

Needle-biopsy cytology in the preoperative diagnostics of breast diseases.

The author has performed 1000 breast needle-biopsies during a period of 20 years. Based on his own experiences and on the data of the literature the method is evaluated as a useful, informative and complementary tool in the preoperative diagnosis of breast diseases. The method is reliable, quick, painless and performable on out-patients, it causes no dissipation of the tumour, therefore, it is recommended as a routine diagnostic method.

Biopsy, Needle↗

PubMed1986

Magnetic resonance imaging in the diagnosis of breast disease.

Magnetic resonance imaging (MRI) of the breast was performed in 10 volunteers and 102 women with suspected breast disease, using a 0.35-T superconducting magnet. All patients had prior x-ray mammography. MRI was superior to mammography in differentiating solid from cystic lesions and equivalent to mammography in providing information regarding different parenchymal patterns. Of 21 surgically proven carcinomas of the breast, MRI correctly identified 18 and mammography identified 19. The major disadvantage of MRI is its inability to show calcifications, benign or malignant. Future studies will be needed to show the relative values of sonography and MRI in detecting small cysts. In addition, MRI in future should be able to demonstrate small, noncalcified masses in mammographically dense, fibrocystic breasts.

Adenofibroma↗

PubMed1982

Distribution of myoepithelial cells and basement membrane proteins in the normal breast and in benign and malignant breast diseases.

An immunocytochemical method for fixed and paraffin-embedded human breast biopsies is reported for the detection of myoepithelial and epithelial cells using antibodies to myosin and keratin, respectively, and of basement membranes using antibodies to laminin and type IV collagen. Using these markers, myoepithelial cells can be clearly distinguished in the normal breast and in the benign breast diseases sclerosing adenosis, epitheliosis, and fibroadenoma. In sclerosing adenosis, myoepithelial cells form a major cellular component. A stromally derived spindle cell is identified which stains with myosin but not with keratin antibodies (myofibroblast). These cells are seen in one-fifth of the fibroadenomas. Although cells staining with myosin antibodies are seen in the infiltrating component of all 18 carcinomas examined, elongated cells staining with both myosin and keratin antibodies (myoepithelial-like) are seen in only one infiltrating carcinoma where they are interposed at the stromal-epithelial junction of the infiltrating tumor cells. In contrast to the situation in benign breast diseases, mature myoepithelial cells form a very minor component of the majority of infiltrating ductal carcinomas. Basement membrane proteins, laminin, and type IV collagen are present in normal breast, benign breast disease, and grade I infiltrating ductal carcinomas but are absent in carcinomas of grades II and III.

Basement Membrane↗

PubMed1984

Oral contraceptives and benign breast disease: a case-control study.

The relationship between benign breast disease and use of oral contraceptives was analyzed in a case-control study conducted in Milan with 288 cases of clinically relevant and histologically confirmed benign breast disease and 285 age-matched controls with a spectrum of acute conditions apparently unrelated to use of oral contraceptives. Compared to the risk for women who had never used oral contraceptives, the relative risk for users was 1.0 (95% confidence interval: 0.6 to 1.5). There was no significant association with duration of use; however, a significantly lower relative risk was found in women using oral contraceptives during the year before breast biopsy (relative risk: 0.4; 95% confidence interval: 0.2 to 0.8). The protection in current users increased with increasing duration of use. In spite of this finding, the overall results of the present study do not support the hypothesis that oral contraceptive use protects against development of histologically confirmed and clinically relevant benign breast disease.

Adolescent↗