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PubMed2005

The use of Compton scattering to differentiate between classifications of normal and diseased breast tissue.

This study describes a technique for measuring the electron density of breast tissue utilizing Compton scattered photons. The Kalpha2 line from a tungsten target industrial x-ray tube (57.97 keV) was used and the scattered x-rays collected at an angle of 30 degrees . At this angle the Compton and coherent photon peaks can be resolved using an energy dispersive detector and a peak fitting algorithm. The system was calibrated using solutions of known electron density. The results obtained from a pilot study of 22 tissues are presented. The tissue samples investigated comprise four different tissue classifications: adipose, malignancy, fibroadenoma and fibrocystic change (FCC). It is shown that there is a difference between adipose and malignant tissue, to a value of 9.0%, and between adipose and FCC, to a value of 12.7%. These figures are found to be significant by statistical analysis. The differences between adipose and fibroadenoma tissues (2.2%) and between malignancy and FCC (3.4%) are not significant. It is hypothesized that the alteration in glucose uptake within malignant cells may cause these tissues to have an elevated electron density. The fibrotic nature of tissue that has undergone FCC gives the highest measure of all tissue types.

Adipose Tissue↗
PubMed1994

Chromosomal aneuploidy in proliferative breast disease.

Although some forms of proliferative breast disease have been associated with increased risk of breast cancer, substantial confirmatory evidence that the lesions are biologically premalignant has not been presented. Our intent was to identify cytogenetic aberrations in proliferative breast disease using fluorescence in situ hybridization probes selected for their relationship to aberrations previously reported in breast cancer. Application of fluorescence in situ hybridization techniques to paraffin tissue sections using pericentromeric probes for chromosomes 1, 16, 17, 18, and X revealed chromosome aneuploidy in proliferative and malignant lesions of the breast. Sectioning artifact that may result in nuclear truncation was controlled by establishing expected baseline frequencies for gain and loss in normal tissues from the same breast. Localization of chromosomal aberrations to proliferative breast disease lesions with concomitant retention of a normal chromosome complement in corresponding normal breast tissues indicates biologic significance of the results. The similarities of losses involving chromosomes 16, 17, and 18 in hyperplastic lesions and in malignant breast lesions suggest that some hyperplasias may be part of a sequence of progression to malignancy in breast cancer. Gains of chromosome 1 in both in situ and invasive carcinoma are consistent with reports of polysomy 1q as a common cytogenetic change in breast cancer. Its localization to advanced lesions suggests that this trisomy is probably not the initial cytogenetic change in breast cancer tumorigenesis.

Aneuploidy↗
PubMed1982

Cell-mediated immunity to mouse mammary tumor virus antigens by patients with hyperplastic benign breast disease.

Peripheral blood leukocytes of patients with preoperative breast cancer, benign breast disease, and benign gynecologic disorders and normal healthy females were tested, as blind coded specimens, with murine mammary tumor virus (MuMTV) antigens in the direct and indirect leukocyte migration inhibition (LMI) assays. The incidence of reactivity by patients with breast cancer was low. (From 5 to 35% breast cancer patients reacted, depending on which group of control individuals they were compared to and what antigen was used.) Nonparametric analyses showed no differences between control groups (normal donors and patients with gynecologic disorders) and breast cancer patients with either assay. However, there was a significant difference between benign breast disease patients with hyperplasia and 1) benign breast disease patients without hyperplasia (P less than 0.03) and 2) patients with gynecologic disorders (P less than 0.04) in the direct assay when it was performed blindly with the gp52 antigen. Patients with hyperplasia (benign breast disease as well as breast cancer) had a higher incidence of enhanced migration in the indirect test than breast disease patients without hyperplasia. The enhanced migration to the MuMTV was correlated to enhanced migration to a 3-M KCI extract of the breast cancer cell line MCF-7 in simultaneous tests. Thus the LMI assays with MuMTV antigens do not appear valuable in breast cancer diagnosis, but they may help to identify a small group of benign breast disease patients whose breast pathology is thought to be associated with a high risk for developing breast cancer.

Antigens, Viral↗
PubMed1982

The LAI test in specific immune-reactivity studies of fibrocytic breast disease.

Sixteen cases of fibrocystic breast disease at different histopathologic stages were examined with the leukocyte adherence inhibition assay. Skeletal muscle and gastric carcinoma extracts were used as controls. The glass adherence of leukocytes from patients affected by fibrocystic breast disease was more inhibited when extracts from breasts with fibrocystic disease were used rather than control extracts. Nonadherence indexes (NAIs) were high in 8 cases, around 20 in 4 cases, a little above zero in 2 cases and below zero in 2 cases. NAIs were related to the histopathologic stage: the highest NAIs were found in 8 cases of classic fibrocystic disease, the lowest in 1 case of simple breast fibrosis.

Breast Diseases↗
PubMed2005

Human gross cyst breast disease and cystic fluid: bio-molecular, morphological, and clinical studies.

For more than one and a half century the cystic disease of the breast has been recognized as the most frequent female benign breast lesion. Although some conundrums and controversies exist about the relation between gross cysts and breast cancer, recent evidence suggests that the multidisciplinary study of gross cystic breast disease (GCBD) may be a powerful tool for predicting the natural history of the multifaceted gross cyst pathology. A lot of papers have been published on breast cyst fluids (BCF) concerning biochemical, hormonal and morphological aspects, demonstrating that the intracystic fluid contains a wide variety of components (such as ions, lipids, proteins, enzymes, growth factors and antigens) and suggesting that their profile provides additional knowledge on both physiopathology and etiologic pathways of human gross cystic breast disease. The aim of this overview is the critical evaluation of all data accumulated in the last thirty years, in order to highlight the utility of biochemical and epidemiological studies to identify gross cysts, if any, at higher breast cancer risk.

Biomarkers, Tumor↗
PubMed2001

Breast disease in sarcoidosis.

BACKGROUND: Breast disease in sarcoidosis can be classified as sarcoidosis patients with breast granulomas, sarcoidosis patients with breast cancer, and breast cancer patients displaying sarcoidosis-like breast reactions. METHODS: We reviewed the medical records of 629 women with sarcoidosis followed in the Interstitial Lung Disease Clinic at the University of Cincinnati for findings associated with breast disease. In addition, three women with breast cancer who had granulomas in proximity to their tumors were also examined. RESULTS: Abnormal breast examinations or mammograms were reported in 15 patients with sarcoidosis (2% of women with sarcoidosis). Breast biopsy revealed granulomas consistent with sarcoidosis in six. One of them developed breast cancer five years later. Breast cancer was identified in twelve further patients, therefore a total of thirteen patients with breast cancer were identified. Ten were diagnosed with breast cancer plus sarcoidosis: sarcoidosis preceded breast cancer in three, followed breast cancer in five, the two diseases appeared simultaneously in two. Three additional women with breast cancer were also evaluated and classified as patients with sarcoid-like reaction. Review of the mammographic and physical findings could not distinguish between sarcoidosis in the breast and breast cancer. CONCLUSION: Sarcoidosis patients develop breast cancer at the expected frequency. The breast cancer diagnosis may precede or follow that of sarcoidosis. There is no relationship between stage of sarcoidosis or treatment and the development of cancer. Because physical examination and mammography findings are unable to distinguish between sarcoidosis and malignancy, biopsy of all suspicious lesions in sarcoidosis is recommended.

Adrenal Cortex Hormones↗
PubMed2000

Mammographic densities and the prevalence and incidence of histological types of benign breast disease. Reference Pathologists of the Canadian National Breast Screening Study.

There is now a large amount of evidence indicating that women with extensive areas of mammographic densities are 4-6 times more likely to develop breast cancer than those with little or no density in the mammogram. We have examined one potential biological explanation for this association by estimating the incidence of various histological types of benign breast disease in relation to mammographic density. We studied the large cohort of women taking part in the National Breast Screening Study (NBSS), a randomized trial of screening with mammography. Mammograms from subjects with biopsies (n = 423) and from a comparison group of subjects randomly selected from the NBSS (n = 465) were included. Histological slides from biopsied subjects (n = 353) were classified independently by the pathologists of the NBSS and by a review pathologist (H.M.J.). Mammographic density in more than 75% of the breast area was associated with an increased risk of incidence of hyperplasia without atypia, and of atypical hyperplasia and/or carcinoma in situ. The classifications of the review pathologist showed that, compared to women with no density, the relative risk of incident lesions for women with density in more than 75% of breast was 13.85 (95% CI 2.65-72.49) for hyperplasia, and 9.23 (95% CI 1.66-51.48) for atypical hyperplasia and/or carcinoma in situ. These findings suggest that the association between extensive mammographic density and breast cancer risk may, at least in part, be attributable to biological processes in the breast that give rise to these histological features that are known to be related to breast cancer risk.

Adult↗
PubMed2005

Timing of critical genetic changes in human breast disease.

BACKGROUND: Breast cancer development has been characterized as a nonobligatory sequence of histological changes from normal epithelium through invasive malignancy. Although genetic alterations are thought to accumulate stochastically during tumorigenesis, little is known about the timing of critical mutations. This study examined allelic imbalance (AI) in tissue samples representing a continuum of breast cancer development to examine the evolution of genomic instability. METHODS: Laser-microdissected DNA samples were collected from histologically normal breast specimens (n = 25), atypical ductal hyperplasia (ADH, n = 16), ductal carcinoma-in-situ (DCIS, n = 37), and stage I to III invasive carcinomas (n = 72). Fifty-two microsatellite markers representing 26 chromosomal regions commonly deleted in breast cancer were used to assess patterns of AI. RESULTS: AI frequencies were <5% in histologically normal and ADH specimens, 20% in DCIS lesions, and approximately 25% in invasive tumors. Mann-Whitney tests showed (1) that levels of AI in ADH samples did not differ significantly from those in histologically normal tissues and (2) that AI frequencies in DCIS lesions were not significantly different from those in invasive carcinomas. ADH and DCIS samples, however, differed significantly (P < .0001). CONCLUSIONS: DCIS lesions contain levels of genomic instability that are characteristic of advanced invasive tumors, and this suggests that the biology of a developing carcinoma may already be predetermined by the in situ stage. Observations that levels of AI in ADH lesions are similar to those in disease-free tissues provide a genomic rationale for why prevention strategies at the ADH level are successful and why cases with ADH involving surgical margins do not require further resection.

Allelic Imbalance↗
PubMed1993

Breast implants, common complications, and concurrent breast disease.

Recent concern regarding breast implants has emphasized the special imaging needs of the approximately 2 million American women who currently have prosthetic breast implants, including silicone gel, silicone gel with a textured silicone coating, saline, biocompatible gel, polyurethane-coated, double-lumen, and tissue expanders. Both palpable and nonpalpable breast lesions can occur in patients with implants, and these lesions must be evaluated in the same manner as in patients without implants, which presents a challenge for the mammographer. Not only is the breast tissue of a patient with implants more difficult to image, but the patient may have complications from the implants. The major complications of their use involve hematoma in the early postoperative period, infection, capsule contracture, rupture, and silicone granulomas. Familiarity with the more common types of implants, the possible complications of their use, and concurrent breast disease may help improve diagnosis in these patients.

Adult↗
PubMed1986

The accuracy of ultrasound in the diagnosis of breast disease.

The accuracy of breast ultrasound using all purpose static beta-scanning equipment has been compared with mammography. Ultrasound was found to be both more sensitive (93%:82%) and specific (95%:89%) in a large retrospective series of 1000 patients undergoing investigation for symptomatic breast disease. In a smaller prospective and consecutive series of 142 patients undergoing surgery where histological proof was obtained ultrasound was also found to be more sensitive (91%:81%) and specific (81%:69%). In both studies, the greater accuracy of ultrasound was attributed to its ability to diagnose lesions hidden in X-ray dense breasts and where mammography had revealed featureless asymmetical densities of uncertain nature. In these instances ultrasound may have a significant role to play as an adjunct to mammography in the preoperative assessment of breast lesions.

Breast Diseases↗
PubMed1978

Immunologic relationship between breast carcinoma and benign breast disease as detected by the leukocyte migration inhibition assay.

Patients with benign diseases of the breast reacted in a migration inhibition assay with extracts of breast cancer and benign breast lesions and a human breast cancer-derived cell line, MCF-7. The incidence of reactivity of the patients with benign breast diseases against these antigens was similar to that of breast cancer patients. In addition, patients with breast cancer reacted to some extracts of benign breast lesions. The reactivity occurred in patients with several different histopathologic types of breast lesions, but was not found in women with no detectable pathologic lesions.

Adenofibroma↗
PubMed1995

Dose- and time-response for breast cancer risk after radiation therapy for benign breast disease.

Exposure of the breast to ionising radiation increases the risk of breast cancer, especially among young women. However, some issues remain controversial, for instance the shape of the dose-response curve and the expression of time-related excess. The main purpose of this report was to examine the dose-response curves for radiation-induced breast cancer formulated according to radiobiological target theories. Another purpose was to analyse the time-related excess of breast cancer risk after exposure when dose and age at first exposure were held constant. Breast cancer incidence was analysed in a cohort of 3090 women diagnosed with benign breast disease during 1925-61 (median age 37 years). Of these, 1216 were treated with radiation therapy. The dose range was 0-50 Gy (mean 5.8 Gy). The incidence rate as function of dose was analysed using a linear-quadratic Poisson regression model. Cell-killing effects and other modifying effects were incorporated through additional log-linear terms. Additive and multiplicative models were compared in estimating the time-related excess. The analysis, which was based on 278 breast cancer cases, showed a linear dose-response relationship at low to medium dose levels with a cell-killing effect of 5% Gy-1 (95% confidence interval 2-9%). For a given absorbed dose and age at first exposure the time-related excess was proportional to the background rates with a suggestion that the excess remains throughout life.

Adolescent↗
PubMed1992

Histological pattern of benign breast disease as a risk factor for invasive breast cancer.

Morphological criteria for histologic diagnosis of both typical and atypical breast epithelial hyperplasias have recently been thoroughly reviewed. Typical epithelial hyperplasia ranges from mild to florid and is characterized by a lack of cytologic atypia. Atypical hyperplasia (AH) is a borderline epithelial lesion between typical hyperplasia and carcinoma in situ. AH represents the most important histopathologic predictor of future breast cancer (BC) according to a case-control study we have recently carried out in a cohort of women previously treated for histologically confirmed benign breast disease (BBD). The use of histologically defined categories in order to predict BC risk depends on the utilization of strict and uniform diagnostic criteria that are currently far from being defined and widely accepted as shown in studies of inter-observer variability among pathologists. Further studies are needed to evaluate inter-observer reproducibility and to assess BC risk among women with different BBD types.

Breast Diseases↗
PubMed1998

Altered expression of c-erbB-2, DF3, b72.3, p53 and Ki-67 with progression and differentiation to two distinct histologic types of invasive carcinoma in the MCF10AT human xenograft model of proliferative breast disease.

Human breast epithelial MCF10AT cells form simple ducts in nude/beige mice which eventually become hyperplastic and sporadically progress to carcinomas. Altered immunohistochemical detection of c-erbB-2, DF3, B72.3, p53 and Ki-67 was observed with progression and differentiation to two distinct histologic types of invasive carcinoma. c-erbB-2 and DF3 were detected in 50% and 18% of lesions at the stage of atypical hyperplasia and expression increased to 78% and 54% in invasive adenocarcinomas. In contrast, a group of six unusual undifferentiated tumors with squamoid features did not express c-erbB-2 or DF3, but both B72.3 (4/6) and p53 (6/6) were detected.

Adenocarcinoma↗
PubMed1997

Pictorial review: the imaging features of male breast disease.

Although breast carcinoma in men is rare, the presentation of a male patient with evidence of breast enlargement or of a palpable lump, is not uncommon. In such patients, radiological assessment may be requested to exclude malignant change. Mammography has been traditionally the dominant modality of investigation, although ultrasound, using high-frequency linear transducers, is playing an increasingly important role for both imaging and biopsy and the two techniques should be regarded as complementary. In this article the pathological conditions which may affect the male breast are reviewed and the imaging findings presented.

Adult↗