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Differential distribution of soluble and complexed forms of prostate-specific antigen in cyst fluids of women with gross cystic breast disease.

Gross cystic breast disease (GCBD) is the most common benign disease of the human female breast, and patients with GCBD have an increased risk of breast cancer. The aim of this study was to evaluate the distribution inside apocrine cells and in breast cyst fluids aspirated from gross cysts of prostate-specific antigen (PSA) molecular forms, and to correlate the different intracystic PSA profiles to the subpopulations of gross cysts. Type I cysts showed a median value of 0.71 microg/L of total PSA and 0.32 g/L of ACT, significantly different to that of Type II cysts (Wilcoxon P < 0.001). Although large excesses of ACT were detected in all samples, BCF samples and apocrine cells from Type I gross cysts contained about 70% of free PSA, compared to the higher amounts of complexed PSA found in Type II gross cysts. We demonstrate that in apocrine/secretive Type I breast gross cysts the serine protease PSA was mainly present in its free form, in contrast to a major proportion of complexed PSA found in flattened/transudative Type II cysts. Our results are consistent with the notion that a prolonged exposure of apocrine breast cells lining the Type I gross cysts to the proteolytic activity of PSA could be involved in the etiopathogenesis of GCBD.

Adult↗

The appearances of benign breast diseases on ultrasound.

BACKGROUND: Benign breast diseases are common and Ultrasound is a very useful tool in examining benign breast diseases especially in distinguishing solid from cystic masses. This study aims to determine the sonographic pattern of benign breast diseases in a Nigerian population and to compare this pattern with that which has been previously reported in other environments. METHODS: This a prospective study of Ninety-four patients with breast disease scanned between 1997 and 2001 on request from the breast clinic of the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife. A total of forty-four patients with histologicaly confirmed benign breast diseases were selected for this study. Their ultrasonographic features were evaluated and compared with those previously described. RESULT: Fibroadenoma was the commonest disease, occurring in 62.2% of the patients, with a mean age of 29.1 years, an age higher than that previously reported. Other diseases which were expected to occur commonly (breast abscess, cyst) were rarely seen. CONCLUSION: While it was discovered that the sonographic pattern of most of the diseases in this study conformed to that already described in literature despite late presentation, only one sonographic appearance of galactocele, out of the three reported, was noted in this study. In addition, despite the nonspecificity of ultrasound appearances in fibrocystic disease, an attempt has been made to match these appearances with the different histological types already described in literature.

Adolescent↗

Beyond fibrocystic disease. The evolving concept of pre-malignant breast disease.

There is a broad spectrum of benign and pre-malignant breast disease that may be diagnosed on biopsy. Some of these conditions place affected women at significantly increased risk for breast cancer, particularly the atypical hyperplasias. All health care workers should be aware of recent developments in this important aspect of breast disease. The classification, criteria for diagnosis, associated risks for cancer development and various controversies related to these benign and borderline breast diseases are discussed.

Breast↗

Tamoxifen responders selection by computerized contact thermography in benign breast disease.

Initial thermic breast values recorded by contact thermography in 29 premenopausal patients with benign breast disease were compared to those recorded 4 and 24 hours after a single 20 mg tamoxifen oral administration. Programmes worked out by the thermographic Prometheus computerized system processed the thermic values. The data obtained were analyzed and compared to the clinical effects resulting from 2 or 3 tamoxifen therapeutic cycles subsequently administered to these patients. The results obtained so far are indicative of the possibility to differentiate by thermographic means the responders from non-responders to subsequent tamoxifen-therapy for breast benign disease.

Adenofibroma↗

Lower-category benign breast disease and the risk of invasive breast cancer.

BACKGROUND: The risk of invasive breast cancer associated with benign breast disease (BBD) other than atypical hyperplasia and in situ breast cancer, especially with nonproliferative diagnosis, has not been explored extensively. This report evaluates the risk of breast cancer associated with this lower-category BBD (LC-BBD). METHODS: 11 307 women without prior history of atypical hyperplasia or in situ breast cancer at randomization (1992-1997) were identified from the cohort of the National Surgical Adjuvant Breast and Bowel Project's Breast Cancer Prevention Trial. Pathologic findings from breast biopsy reports through August 2002 were reviewed, and Cox proportional hazards models were used to determine the relative risks (RRs) of breast cancer with 95% confidence intervals (CIs). The relative risks of breast cancer for LC-BBD were adjusted for treatment and for breast cancer risk as determined by the modified Gail model. RESULTS: Of the 11 307 women, 1376 had LC-BBD, of whom 47 developed breast cancer, and of the 9931 women without LC-BBD, 291 developed breast cancer. The RR of breast cancer for women with LC-BBD relative to women without LC-BBD was 1.60 (95% CI = 1.17 to 2.19). Among women 50 years of age and older, the RR of breast cancer for those with LC-BBD was 1.95 (95% CI = 1.29 to 2.93). After adjustment for treatment and breast cancer risk, the RR of breast cancer for women with LC-BBD was 1.41 (95% CI = 1.03 to 1.94). CONCLUSIONS: Women with LC-BBD had a statistically significant increased risk of breast cancer. The elevation of breast cancer risk was especially evident in women 50 years of age and older. Furthermore, this risk was independent of that associated with key epidemiologic breast cancer risk factors.

Adult↗

Impact of fine-needle aspiration cytology, ultrasonography and mammography on open biopsy rate in patients with benign breast disease.

The management of breast disease has been influenced by breast imaging and fine-needle aspiration cytology (FNAC) for preoperative diagnosis. To investigate the impact of introducing an in-clinic FNAC service on patient management, the pathology records of patients presenting before and after introduction of the service were studied. Four management changes emerged. The number of patients investigated by histology and/or cytology increased (from 266 to 503), as did specimen numbers (392 to 728). The use of pathological services changed, with more cytology specimens (39 to 554), fewer needle-core biopsies (62 to three) and fewer excision biopsies (245 to 118). The number of patients admitted for surgery fell, especially those with a benign histological diagnosis (174 to 49). These figures demonstrate a change in the management of benign breast disease, from surgery with histopathological diagnosis to cytological diagnosis with surgery only if indicated clinically or from imaging.

Adolescent↗

Interactions between benign breast disease and other risk factors for breast cancer.

A population-based incident case-control study of breast cancer in Northern Alberta, Canada, provided an opportunity to evaluate interactions between the occurrence of benign breast disease (BBD) and other potential risk factors. Overall there was a 2-fold excess risk of breast cancer among women with BBD. This excess persisted regardless of the number of years from first biopsy for BBD to diagnosis of breast cancer, suggesting a permanent alternation in risk with BBD. Significant variations of the BBD--breast cancer association were noted with several factors. The excess risk of breast cancer among women with BBD was enhanced by having a later age at menarche, a later age at first birth, or lower parity. The usual protective effect of late age at menarche was seen only among women without BBD, and was supplanted by a 4-fold elevated risk among women with BBD. The deleterious effects of later age at first birth and nulliparity were greater among women with BBD. These patterns generally support the notion that hormonal factors mediate the relation between BBD and the development of breast cancer.

Adult↗

Effect of natural "micronized" progesterone on the chorionic gonadotropin concentrations in cyst fluids of women with gross cystic breast disease.

Gross cystic breast disease (GCBD) is common in women, especially in the age range between 35 and the menopausal years. The present study examined the possible role of progesterone (Pg) in the chorionic gonadotropin (hCG) concentration in GCBD. The breast cyst fluids (BCFs) were drawn by fine needle aspiration between the sixth and the eighth day of the menstrual cycle and twenty days later. On the day of the first aspiration the patient began to take 100 mg of natural micronized Pg orally until the second aspiration. At both times blood samples were also taken. Determinations were done of both BCFs and blood sample using two fully automated chemiluminiscent enzyme immunometric assays. Pg has been demonstrated to induce a significant increment in hCG + free ss-hCG (median, range): 0.27 ng/ml, 0.12-6.24 vs. 1.92 ng/ml, 0.12-423.5; free ss-hCG: 0.11 ng/ml, 0.02-2.40 vs. 0.91 ng/ml, 0.02-58.40 in the BCFs, with no change in the circulating concentrations of the hormone. None of the sera studied presented levels of hCG + free ss-hCG or free ss-hCG above 0.5 ng/ml or 0.1 ng/ml, respectively. The occurrence of hCG or a derivative polypeptide in BCFs, when they are present in high concentrations suggests that this glycoprotein could be synthesized in situ and possibly involved in the pathogenesis of GCBD by the degree of differentiation of breast epithelial cells induced by the hormone.

Administration, Oral↗

Benign and malignant breast disease: initial study results of serum and breast fluid analyses of endogenous estrogens.

Design, methods, and study population of a long-term multidisciplinary investigation of benign and malignant breast disease were reported. This initial report focused on the relation of menstrual, reproductive, and other factors to serum and breast fluid estrogen measures [estradiol (E2), estrone (E1), percent free estrogen, and sex hormone binding globulin] among control women. After adjustment for the factors found to be related to the various estrogen measures, estrogen levels in women with benign and malignant disease were compared to those of controls. Findings were as follows: a) little evidence of any relation of most breast cancer risk factors with the various serum estrogen parameters studied; b) differences in breast fluid estrogen levels that may be relevant to the protective effect of parity on breast cancer risk; c) markedly higher levels of E2 and E1 in breast fluid than in serum and no evidence of a correlation of serum with breast fluid measures; d) no support for the hypothesis that breast cancer patients have higher serum percent free E2 than controls or women with benign breast disease; and e) higher breast fluid E2 and E1 levels in women with biopsied benign breast disease than in controls.

Adult↗

The relationship of estrogen and progesterone to breast disease.

The rising incidence of breast cancer, coupled with awareness of the effects of hormones on breast tissue, has resulted in fears that estrogen, progesterone or both incite or adversely affect benign and malignant breast disease. An intensive review of the hormone physiology of the breast and of the numerous studies on hormones and breast disease reveals that estrogen and especially oral contraceptives not only do not cause breast cancer but may have a slight protective effect. Also, the overwhelming evidence is that the risk of benign breast disease is substantially reduced in both current and prior users of oral contraceptives.

Breast Neoplasms↗

Ultrastructural characterization and biochemical profile of human gross cystic breast disease.

Human gross cystic breast disease is a benign condition affecting about 7-10% of adult women occurring with the highest incidence in the premenopausal decade. Although breast cysts do not represent a preneoplastic condition per se, several studies indicate an increased breast cancer risk in women affected by this pathology. In this report we study 115 breast cystic fluid samples obtained by needle-aspiration from women with gross cystic breast disease. The samples were analysed biochemically and the cells contained therein were observed at the electron microscope. According to their biochemical profiles, the cysts were subdivided into three types: Type I, showing a Na/K ratio < 0.5 and a typical protein content; Type II, showing a Na/K ratio >10 and a protein content quite similar to plasma; Type III, showing a Na/K ratio between 1 and 7 and an intermediate protein content. The electron microscopic examination demonstrated that Type I cystic fluid cells exhibit morphological features typical of actively synthesising and secreting cells, while the characteristics of Type II cells indicate a low metabolic activity. Type III cells have characteristics typical of both Type I and Type II cells, thereby confirming the intermediate nature of this cyst type. We hypothesise that these cyst types could represent different developmental stages of a structural evolution pathway, during which the biosynthetically active 'apocrine stage' would be the key step to cell neoplastic transformation.

Adult↗

Influence of exogenous estrogens, proliferative breast disease, and other variables on breast cancer risk.

The authors reevaluated 10,366 consecutive breast biopsy specimens of benign lesions performed between 1950 and 1968. Follow-up information was obtained on 3303 women with a median duration of follow-up of 17 years. This sample contained 84% of the patients originally selected for follow-up. The relative risk (RR) of developing breast cancer was 0.98 for women who took exogenous estrogens as compared to 1.8 for women who did not. Exogenous estrogens lowered the observed breast cancer risk in women with atypical hyperplasia (RR = 3.0 versus 4.5), proliferative disease without atypia (RR = 0.92 versus 1.9), and in women without proliferative disease (RR = 0.69 versus 0.91). Women who took estrogens before 1956 were at 2.3 times the risk of other estrogen users, presumably due to a dose effect. There was no significant association between breast cancer risk and birth control pills, cigarette smoking, or alcohol consumption. Exogenous estrogens are not associated with increased breast cancer risk in women with benign breast disease. A previous history of benign breast disease does not contraindicate replacement estrogen therapy.

Adult↗

Study of benign breast disease in a population screened for breast cancer.

We are conducting a study to determine whether risk factors associated with specific pathologic subtypes of benign breast disease (BBD) are similar to those for breast cancer and to evaluate the relationship between clinical and mammographic features of BBD. All women participating in the Canadian National Study of Breast Cancer Screening in Vancouver, B.C., Canada (expected 10,000) are invited to complete a questionnaire designed to gather clinical and epidemiologic information on BBD. Preliminary analysis of the first 736 participants indicates that breast pain and/or tenderness is a significant problem which in its severe from is distressing, anxiety provoking, and adversely affecting quality of life. Breast pain and tenderness is also associated with an increased frequency of clinical signs of BBD and of dense mammographic patterns.

Adult↗

Breast diseases and the internist.

Benign breast disease affects almost all women, although only one out of 11 will eventually develop breast cancer. Fibrocystic disease or benign breast mastopathies have been associated with an increased propensity to progress to malignancy. However, the increased relative risk for women with benign breast disease developing breast cancer appears to be associated with proliferative benign disease in association with atypia. Their cumulative risk may be as high as 30%. These women represent 3-5% of women with benign disease. They clearly warrant more careful screening and follow-up. The etiology of benign breast mastopathies is unknown, but its incidence and relationship to hormonal events suggests that many of the histologic entities represent an endocrine response. Many hormonal manipulations have been shown to decrease mastodynia and reduce the incidence of breast aspirations and biopsies. However, these and other therapeutic interventions have not been shown to reduce the incidence of breast cancer in women who are at high risk.

Adult↗

Progressive resistance to apoptosis in a cell lineage model of human proliferative breast disease.

BACKGROUND: Proliferative breast disease (PBD) may increase a woman's risk of developing breast cancer, perhaps by decreasing cellular sensitivity to apoptosis. To determine whether resistance to apoptosis develops during PBD, we investigated apoptosis initiated through the Fas pathway in a series of cell lines that recapitulates the morphologic changes of PBD in nude/beige mice. METHODS: The series of cell lines used was MCF-10A cells (parental preneoplastic human breast epithelial cells), MCF-10AT cells (transformed with T(24) Ha-ras), and MCF-10ATG3B cells (derivative cells that progress to carcinoma). Fas-mediated apoptosis, induced when a Fas monoclonal antibody bound to and activated the Fas receptor on these cells, was assessed morphologically and by flow cytometry. Levels of proteins involved in Fas-mediated apoptosis and cleavage of poly(adenosine diphosphate-ribose) polymerase (PARP), an end product of caspase activation, were determined by immunoblotting. Bcl-2 and Bax heterodimerization was examined by coimmunoprecipitation. All statistical tests were two-sided. RESULTS: Sensitivity to Fas-mediated apoptosis decreased with the tumorigenic potential of cells: MCF-10A cells were extremely susceptible, MCF-10AT cells were less susceptible, and MCF-10ATG3B cells were resistant. The percentage of apoptotic cells declined, from 24% to 8% to 6%, respectively. All lines produced Fas ligand (FasL) and had comparable levels of Fas receptor, FasL, Fas-associated death-domain protein, and caspases 3 and 6. Levels of caspase 8 were similar in MCF-10A and MCF-10AT cells but about 30% lower in MCF-10ATG3B cells (P>.01 but <.05). Levels of caspase 10 were about 20% lower in MCF-10AT cells (P>.005 but <.01) and about 59% lower in MCF-10ATG3B cells than in MCF-10A cells (P>.01 but <.05). PARP cleavage was detected in MCF-10A and MCF-10AT cells but not in MCF-10ATG3B cells. Levels of Bax, Bid, and Bak proteins were similar in all lines, but levels of Bcl-2 were lower in MCF-10AT and MCF-10ATG3B cells than in MCF-A cells, and Bcl-2-Bax heterodimerization progressively declined in the series. CONCLUSION: Resistance to Fas-mediated apoptosis appears to develop progressively in the MCF-10AT cell series.

Adaptor Proteins, Signal Transducing↗