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PubMed1999

Percutaneous progesterone use and risk of breast cancer: results from a French cohort study of premenopausal women with benign breast disease.

Percutaneous progesterone topically applied on the breast has been proposed and widely used in the relief of mastalgia and benign breast disease by numerous gynecologists and general practitioners. However, its chronic use has never been evaluated in relation to breast cancer risk. The association between percutaneous progesterone use and the risk of breast cancer was evaluated in a cohort study of 1150 premenopausal French women with benign breast disease diagnosed in two breast clinics between 1976 and 1979. The follow-up accumulated 12,462 person-years. Percutaneous progesterone had been prescribed to 58% of the women. There was no association between breast cancer risk and the use of percutaneous progesterone (RR = 0.8; 95% confidence interval 0.4-1.6). Although the combined treatment of oral progestogens with percutaneous progesterone significantly decreased the risk of breast cancer (RR = 0.5; 95% confidence interval 0.2-0.9) as compared with nonusers, there was no significant difference in the risk of breast cancer in percutaneous progesterone users versus nonusers among oral progestogen users. Taken together, these results suggest at least an absence of deleterious effects caused by percutaneous progesterone use in women with benign breast disease.

Administration, Cutaneous↗
PubMed1991

Cytologic identification of clinically occult proliferative breast disease in women with a family history of breast cancer.

A cytologic method for sampling the normal breast by fine-needle aspiration (FNA) was used to determine the frequency of clinically inapparent proliferative breast disease (PBD) in women with family histories of breast cancer. The authors attempted to obtain specimens from each quadrant of both breasts in 51 female first-degree relatives of breast cancer patients. The study group had no detectable masses by physical examination or mammography. Samples were prepared on membrane filters, Papanicolaou stained, and evaluated cytomorphologically. Three hundred seventy-eight of 408 (92.6%) possible quadrants were sampled; cellular material was obtained from 290 (76.7%) quadrants. PBD was identified in 20 of the 51 women (39.2%). When epithelium was obtained, nuclear area, perimeter, and diameter were measured with the use of computerized image analysis. Nuclei in samples containing atypical hyperplasia showed significant differences in these parameters when compared with cells from samples containing normal epithelium or benign hyperplasia. The authors' findings indicate that FNA sampling and computerized image analysis are useful in the detection and characterization of clinically inapparent PBD.

Adipose Tissue↗
PubMed1992

Using biological measurements, can patients with benign breast disease who are at high risk for breast cancer be identified?

In order to address the question of whether biological measurements might identify women with benign breast disease (BBD) at particular risk for breast cancer, analyses were performed on cyst fluids aspirated from patients presenting with palpable breast cysts. Electrolyte profiles showed that cyst fluids may be divided into major subpopulations which differ in terms of histological appearance of cyst lining epithelium, pattern of cyst presentation, and levels of other fluid constituents such as androgen conjugates and epidermal growth factor. Analysis of cyst fluids from 18 patients who subsequently developed breast cancer 1 to 8 years later showed that 12 individuals had group A cysts, three had group B cysts, and three presented with a mixture of the two types. Therefore, although this represents an increased proportion of group A cysts as compared with the total population of cyst fluids studied over the same time period, individuals subsequently developing breast cancer were not confined to one subgroup of cysts. Androgen conjugate and growth factor content also did not predict for subsequent cancer. At the present time, it is therefore concluded that biochemical measurements in cyst fluids cannot accurately identify women likely to develop breast cancer. However, the routine aspiration of cysts does provide the opportunity to monitor the local microenvironment of the breast.

Androgens↗
PubMed1993

Xenograft model of progressive human proliferative breast disease.

BACKGROUND: Progression of proliferative breast disease has been associated with increased risk for development of invasive carcinoma. Cell lines have been developed to facilitate the study of this process. Human cell line MCF10A originated from spontaneous immortalization of breast epithelial cells obtained from a patient with fibrocystic disease, and cell lines MCF10AneoN and MCF10AneoT were created by stable transfection of these cells with the neomycin-resistance gene and either the HRAS gene or the mutated T-24 HRAS gene, respectively. PURPOSE: Our goal was to develop an experimental model of progressive human proliferative breast disease. METHODS: MCF10A, MCF10AneoN, and MCF10AneoT cells were injected subcutaneously into the dorsal flank of male nude/beige (C57/BALB/c nu/nu bg/bg) mice (12 mice for each cell type). These mice were examined periodically for formation and persistence or growth of palpable nodules. One mouse per group was killed 1 week after cell injection; thereafter, mice were observed as long as possible. Cells were recovered from palpable lesions by enzymatic dissociation of the excised lesions. Cells re-established in tissue culture from a week-14 tumor (MCF10AneoT.TG1) were injected into 12 male nude/beige mice. Southern blot hybridization analysis of the HRAS gene locus and cytogenetic analyses were performed. RESULTS: Transplanted MCF10A and MCF10AneoN cells formed transient, small palpable nodules that regressed and disappeared during the 4th and 5th weeks. In 10 of the 12 mice, T-24 HRAS gene-transfected MCF10A cells (MCF10AneoT) formed small, flat nodules that persisted for at least 1 year. Three of these xenografts became carcinomas. One (removed 7 weeks after transplantation) was an undifferentiated carcinoma composed of polygonal cells with large, vesicular nuclei and numerous mitoses. The second (removed after 14 weeks) was an invasive squamous cell carcinoma. The third (removed after 56 weeks) was a moderately differentiated adenocarcinoma. Initially, xenografts of MCF10AneoT.TG1 cells showed intraductal proliferative changes; after 23 weeks, the lesions showed histologic features resembling those seen in atypical hyperplasia of the human breast, and later lesions showed characteristics of carcinoma in situ. The MCF10 lineage of cells of three MCF10AneoT.TG1 xenografts was confirmed by DNA fingerprinting and karyotype analysis. CONCLUSIONS: MCF10AneoT and MCF10AneoT.TG1 comprise a transplantable xenograft model that produces a broad spectrum of human proliferative breast disease. IMPLICATIONS: The reproducible establishment of representative stages in early breast cancer progression from the MCF10 model offers a new opportunity to analyze critical events of carcinogenesis and progression in breast cancer.

Adult↗
PubMed1980

The treatment of benign breast disease with danazol.

Benign breast disease, aside from fibroadenomas and intraductal papillomas, frequently responds favorably to hormonal therapy. Although the use of estrogen, androgens, and progestogens often proves useful, danazol, in our hands, was found more consistently effective. Danazol, an impeded androgen derived from a progestogen, 17 alpha-ethinyltestosterone, was employed in doses of 100 to 400 mg/day for 3 to 6 months in the treatment of fibrocystic disease. This agent proved efficacious in eliminating nodularity in the majority of cases, with partial resolution in most of the others. Many women to whom surgery had been previously suggested were spared surgical interference because of a satisfactory response to danazol therapy.

Adult↗
PubMed1988

[Prolactin--significance in benign and malignant breast diseases].

At present, the role of prolactin has not yet been precisely determined both in the development and in the progression of benign and malignant diseases of the breast. Experimental investigations and data of the human receptor assay have clearly indicated the initial and promoting activity of prolactin in the genesis of breast tumors. However, the data published so far, which is in some cases highly contradictory, does not allow a positive appraisal on the correlation of the prolactin level and breast diseases in clinical research and experimental studies. The studies still to be carried out in human medicine with precise definition of the TRH-prolactin-target cell axis compared with the proof of the receptor radioimmunoassay in healthy and malignant breast tissue which has still not yet been provided might give rise to rather more clarity in this rather manifold problem.

Breast↗
PubMed1996

Office gynecology for the primary care physician, part II: pelvic pain, vulvar disease, disorders of menstruation, premenstrual syndrome, and breast disease.

Approaches to patients with pelvic pain, vulvar disease, disorders of menstruation, premenstrual syndrome, and breast diseases are addressed. In the great majority of cases, it is appropriate for the primary care physician to initiate evaluation and management of these problems. It is hoped that the brief introductions contained here suggest a diagnostic approach to each disorder and guide referral to consultants as needed.

Breast Diseases↗
PubMed1998

Risk factors for benign breast disease according to histopathological type: comparisons with risk factors for breast cancer.

We evaluated risk factors for benign breast disease by using a case-control study method. The series was taken from participants in breast cancer screening programs during 1978-1986 in Miyagi Prefecture, Japan. All benign breast lesions diagnosed during this period were reviewed and reclassified into proliferative and non-proliferative types based on the Dupont and Page classification. Data on 382 benign breast disease cases (130 proliferative-type cases and 252 non-proliferative-type cases) and 1,489 screening year-, age- and screening area-matched normal controls were used for analysis. Nulliparity or low parity and family history of breast cancer in mother or sisters were significantly associated with an increased risk of proliferative type. Premenopausal status was significantly associated with an increased risk of non-proliferative type. No significant association with history of lactation for the last child was observed in either type, but the risk of proliferative type increased with increasing duration of lactation (P=0.08). A comparison between the present findings and the risk factors for breast cancer indicated epidemiologic similarities between proliferative benign and malignant breast lesions in general. The associations of these two lesions with lactation patterns were, however, dissimilar.

Adolescent↗
PubMed1997

[Some aspects of fibrocystic breast disease].

The fibro-cystic disease is very common disease. Hormonal factors: hyperestrogenemia, luteal deficiency, dysprolactinemia are inconstant. They are neither necessary nor sufficient to induce the cystic disease. The relations GCD (gross cystic disease) with breast cancer remain the fundamental problem. Although the cyst itself only exceptionally degenerates into cancer, the presence of macrocystic disease multiplies by 3 to 4 the risk of cancer. A lot of interesting examinations were performed on cyst fluids aspirated from patients to identify women with benign breast disease and particular risk for breast cancer. Electrolyte profiles showed, that cysts fluids may be divided into major subpopulations, which differ in terms of histological appearance of cyst lining epithelium and levels of other fluid constituents. At the present time, the biochemical measurements in cyst fluids aren't popular to identify women likely to develop breast cancer. We should use other diagnostic methods to examine these patients.

Adult↗
PubMed1970

Benign and malignant breast disease in South Wales: a study of urinary steroids.

The levels of aetiocholanolone, androsterone, and 17-hydroxycorticosteroids were measured in women without known disease of the breast, in women with benign breast disease, and in women with primary and advanced breast cancer. Statistical analysis showed there was no difference in the excretion of urinary 17-hydroxycorticosteroids in the various groups of patients. Detailed analysis of the aetiocholanolone and androsterone levels, however, indicated that patients with advanced localized disease excreted significantly less of these 11-deoxy-17-oxosteroids than those in the other groups.

17-Hydroxycorticosteroids↗
PubMedDate not supplied

Treatment of benign breast disease with bromocriptine.

23 women with benign breast disease (fibrocystic disease or fibroadenosis) were treated for three months consecutively with a prolactin inhibitor drug, bromocriptine, at the dose of 2.5 mg every eight hours. Serum prolactin levels were normal before treatment; during treatment prolactin concentrations were significantly suppressed all the day long. 21 out of 23 patients receiving bromocriptine showed marked relief to pain and mammary tension after a few days of treatment; adenomatous of cystic nodules became smaller and softer, often with disappearance of the smaller ones. Two patients failed to respond to treatment. In all positive cases the improvement persisted for at least six months after the end of treatment. No important side effects were observed during the therapy. Our results do not allow any conclusion on the real mechanism of action of bromocriptine in benign breast disease, nevertheless they indicate the possible usefulness of this drug in treating patients with benign breast disease.

Adolescent↗
PubMed1991

Decision support system for the differential diagnosis of breast disease.

The histopathological diagnosis of breast disease is representative of many problems of differential diagnosis encountered in the medical domain. It requires highly trained and experienced experts and is characterized by a large number of features whose presence or absence involves much uncertainty. Computer-based decision support systems intended to function in a consultative capacity during differential diagnosis have had limited success for two fundamental reasons. Firstly, they take an autonomous role and assume that the user has no contribution to make to the problem-solving process. Secondly, the established techniques for representing and reasoning with medical knowledge are of limited suitability in this domain. Such systems are unable to reach a correct diagnosis quickly and often subject the user to a cumbersome dialogue. These are not tolerated by pathologists working under severe time constraints. We first look at the problem-solving methods employed by pathologists in this domain and examine the functionality of traditional expert system methodologies. We then present a cooperative design which allows the pathologists to express his or her ideas within a decision support system whilst gaining assistance in required areas. A novel inference technique based upon the set partitioning technique in hypergraphs is also described. This mathematical method has the ability to cope with the incomplete or inadequate knowledge which is a characteristic of breast disease, whilst directing data gathering in a meaningful manner. In particular this approach can significantly reduce the amount of irrelevant data which the pathologist must enter before a conclusion is reached. Thus it can potentially improve the efficiency and user acceptability of medical expert systems.

Algorithms↗
PubMed2005

Biomonitoring of organochlorines in women with benign and malignant breast disease.

Established risk factors for breast cancer explain breast cancer risk only partially. Organochlorines are considered to be a possible cause for hormone-dependent cancers. A hospital-based case-control study, the first from India, was conducted among 50 women undergoing surgery for breast disease to examine the association between organochlorine exposure and breast cancer risk. Blood, tumor, and surrounding adipose tissue of the breast were collected from the subjects with benign (control) and malignant breast (study) lesions and analyzed to determine organochlorine insecticides using a gas-liquid chromatograph equipped with an electron capture detector. The alpha, beta, gamma, and delta isomers of hexachlorocyclohexane (HCH), p,p'-dichlorodiphenyltrichloroethane (DDT), o,p'-DDT, p,p-dichlorodiphenyldichloroethylene, and p,p'-dichlorodiphenyldichloroethane were frequently detected in three specimens. Total HCH and total DDT levels were higher in the blood of the study group (25 cases) than in those of the controls (25 cases) with only gamma-HCH being significantly different (P<0.05). However, both total HCH and total DDT were higher in the tumor tissues of the controls than in those of the study group; gamma-HCH was significantly different (P<0.05). The level of total HCH (alpha-HCH was significantly different, P<0.05) was higher in the breast adipose tissue of the study group, whereas total DDT was higher in the breast adipose tissue of the control group. The distribution of known confounders of breast cancer including age, body mass index, age at menarche and menopause, duration of breast feeding, and family history related to breast disease did not differ significantly between benign and malignant groups. This pilot study with limited statistical power does not support a positive association between exposure to organochlorines and risk of breast cancer but paves the way for a larger Indian study with greater statistical power encompassing different regions of the country to enable statistically sound conclusions.

Adipose Tissue↗
PubMed2004

Alterations of p53, Bcl-2, and hMSH2 protein expression in the normal breast, benign proliferative breast disease, in situ and infiltrating ductal breast carcinomas in the upper Egypt.

BACKGROUND: Tumorigenesis involves alterations in the tumor suppressor genes (p53), protooncogenes (Bcl-2) and housekeeping genes [human MutS homologue-2 (hMSH2)]. We hypothesized that mammary carcinogenesis involves interactions among p53, Bcl-2 and hMSh2 proteins. In the Upper Egypt, the clinicopathologic features and genetic changes during mammary carcinogenesis are unknown. METHODS: To test our hypothesis and to examine these issues, 53 mastectomy specimens, each entailing normal breast, benign proliferative breast disease (BPBD), duct carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC) were immunostained for p53, Bcl-2 and hMSH2 protein expression. RESULTS: The average age incidence of ductal carcinomas was 43.2 +/- 7.06 years. The tumors were common in the left than right side (1.2:1, respectively, p > 0.05). Infiltrating ductal carcinoma of non-specific type was the most common histologic type. Examination of the average weighted scores in the normal breast, BPBD, DCIS and IDC, respectively, showed: (1) significant upregulation of p53 proteins (0.00 +/- 0.00, 0.00 +/- 0.00, 6.25 +/- 2.42, 6.62 +/- 2.15, p = 0.001), (2) insignificant downregulation of Bcl-2 (6.67 +/- 1.33, 5.17 +/- 2.20, 4.79 +/- 2.27 and 4.42 +/- 2.83, p = 0.37), and (3) significant downregulation of hMSH2 (11.3 +/- 0.75, 10.70 +/- 1.27, 7.11 +/- 1.50 and 7.0 +/- 1.33, p = 0.0006). There were insignificant negative correlations between p53 and both Bcl-2 (r = -0.20, p > 0.05) and hMSH2 (r = -0.15, p > 0.05) protein expression. CONCLUSIONS: In the Upper Egypt: (1) breast cancer had similar clinicopathologic features to those in the high risk regions, and (2) alterations of the p53, Bcl-2 and hMSH2 proteins occur during mammary carcinogenesis.

Adult↗
PubMedDate not supplied

Characteristics of cystic breast disease with special regard to breast cancer development.

BACKGROUND: This prospective study compares the characteristics of cystic disease of the breast (CDB) of patients who developed breast cancer (BCa) during the follow-up (1.25-4 years) period with those who did not. MATERIALS AND METHODS: K+, Na+, albumin, dehydroepiandrosterone (DHA), DHA-sulphate, oestrone, oestradiol, testosterone and progesterone levels were determined in breast cyst fluid (BCF). Patients presented data about their menstrual status, reproductive history, lactation period, date of first and the number of BCF aspirations, gynaecological interventions, use of oral contraceptives, family history of cancer, smoking habits and coffee consumption. The BCa incidence of patients was compared with the expected number of BCas in an age-matched group of 5143 women. RESULTS: Out of 147 patients 6 developed BCa. The standardized incidence rate was 6.29. There were significant differences in testosterone, oestrone and progesterone levels and also reproductive history of patients who developed BCa compared with patients without BCa. CONCLUSION: The above markers outline a subgroup of patients with the highest BCa risk.

Adult↗
PubMed1984

Is fibrocystic breast disease a pre-malignant state?

Fibrocystic disease is the most frequent lesion of the breast. When considered as a single diagnostic entity, benign breast disease has generally been reported to be associated with a relative risk of from 1.5 to 3.0 for breast cancer. Few studies have failed to find any association between fibrocystic breast disease and breast cancer. However, the term fibrocystic breast disease encompasses a variety of histologic changes and accordingly a variety of designations. This lack of a clear classification may account for the divergent results in studies on the relationship between cystic disease and breast cancer. Some investigators have in fact examined the risk of breast cancer among women with various forms of fibrocystic disease. Particularly high risks have been associated with atypical epithelial hyperplasia. There is disagreement among pathologists as to whether ductal papillomas are 'precancerous' or cancerous.

Breast Neoplasms↗
PubMed1994

Evaluation of the expression levels of nm23-H1 mRNA in primary breast cancer, benign breast disease, axillary lymph nodes and normal breast tissue.

Expression levels of nm23-H1 were evaluated in a variety of normal benign and malignant breast tissues by Northern and slot blot. Tissues from 153 patients presenting with palpable breast lesions were studied: 132 primary infiltrating breast cancers, 9 pure duct carcinoma in situ lesions, a phyllodes tumor, 9 benign lesions and 2 local recurrences of carcinoma. In addition to lesional tissue, 49 samples of macroscopically normal breast tissue, 37 axillary lymph nodes and 9 samples from patients undergoing cosmetic reduction mammoplasty were studied. Sets of normal breast tissue, primary tumor and lymph node tissue from individual patients were available for comparison in 37 cases. A wide range of gene expression was detected in the various tissue types. The highest levels of expression were detected in malignant samples with in situ carcinomas being associated with the highest levels of gene expression. The expression levels of nm23-H1 in normal breast tissue were lower than the corresponding tumors from the same patients (p < 0.0005). Benign breast lesions (including 6 fibroadenomas) had levels of gene expression approximating those of the normal tissue samples. Normal axillary lymph nodes had significantly lower levels of nm23-H1 expression than nodes with metastatic deposits (p < 0.03). No significant association was observed between nm23-H1 expression levels and axillary node status in patients with infiltrating carcinoma, although there was a slight trend toward lower nm23-H1 mRNA levels in the node negative group.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Northern↗