epidermal-growth-factor and Fibrocystic-Breast-Disease

The mammary cyst is part of the fibro-cystic disease. Only cysts with a diameter of more than 3 mm would have a pathological significance. Its clinical symptomatology is well known. The clearing puncture is the essential diagnostic and therapeutic act. Mammography, sustained by cystography, furnishes highly worthy information. Thermography and ultra-sonography may also be useful. Its pathogeny is still being very much discussed. Hormonal factors are incriminated: hyperestrogenemia, luteal deficiency, dysprolactinemia are inconstant. They are neither necessary nor sufficient to induce the cystic disease. The titration of TeBG may perhaps open an interesting path for research. The study of intracystic steroids (among which DHEAS) furnishes instructive results. Intracystic glycoproteins, proteins and electrolytes are also the objects of promising research. Recently, the interest lying in the study of EGF, its possible relation to DHEAS and the intracystic Na/K ratio were emphasized. It is also important to notice the presence of cysts with a flat wall or with a hyperplastic wall, of the apocrine type. The psychogenic factors seem to be determining in the cystic flare-ups. The relations with breast cancer remain the fundamental problem. Although the cyst itself only exceptionally degenerates into cancer (cyst-epithelioma), the very presence of a macrocytic disease multiplies by 3 or 4 the risk of cancer. The treatment is composed of psychotherapy, tranquillizers and a clearing puncture of the strained cysts. The administration of phlebotonics, anti-prostaglandins, colostrum extracts, can give substantial results. The author gives details about the part of hormonal treatment as a function of the titrations and the severity of the case. If it appears necessary to block the gonadotropic function, Danazol is a very effective agent. Surgery has but a small place. Indication of subcutaneous mastectomy will rest upon a very severe case-selection.

Topics: Adolescent; Breast Neoplasms; Diagnosis, Differential; Diagnostic Imaging; Epidermal Growth Factor; Female; Fibrocystic Breast Disease; Hormones; Humans; Middle Aged

The purpose of our study was to investigate whether enterolactone does accumulate into breast cyst fluid and whether it correlates with breast cancer risk. We included 258 women who had at least one cyst aspiration and known intracystic cation and epidermal growth factor (EGF) concentration values. For 191 of such women serum aliquots were also available. The median value of serum enterolactone was 17 nM/l (range 1-140 nM/l). The median intracystic level of enterolactone was much higher (63 nM/l, range 0-872 nM/l) and was significantly higher in type I cysts (p = 0.000). This cyst type contained also significantly higher levels of EGF (p = 0.000). A direct relationship was found between serum and cyst fluid enterolactone levels (p = 0.000) and between cyst enterolactone and EGF levels (p = 0.03), the latter correlation being evident especially in type II cysts. Twelve patients in the cohort of women were found to have developed a breast cancer. After univariate analysis breast cancer risk was associated with cyst type and especially with EGF concentration. No association was evident for enterolactone concentration. However, enterolactone concentration appeared to significantly decrease the risk of patients with high EGF concentrations. Our results show that enterolactone does accumulate in breast cysts, and that it modulates the risk related to the intracystic level of EGF, which is confirmed to be a strong predictor of breast cancer risk.

Topics: 4-Butyrolactone; Adult; Aged; Breast Neoplasms; Epidermal Growth Factor; Exudates and Transudates; Female; Fibrocystic Breast Disease; Humans; Lignans; Middle Aged; Odds Ratio; Predictive Value of Tests; Risk Factors; Statistics as Topic

In this study, the blood serum concentrations of histamine (HA) and epidermal growth factor (EGF) of women with fibrocystic changes (FCCs) of the breast were estimated. The control group comprised 32 women (mean age 44.9+/-4.4 years) without any pathologic changes in their breasts. The study group was made up of 81 women (mean age 44.5+/-3.5 years) with FCCs. The changes were divided into three subtypes: fibrous, cystic, and fibrocystic. In women with FCCs the concentrations of HA (P<0.01) and EGF (P<0.01) were significantly higher than in women without any changes in their breasts (control group). The concentration of EGF in blood serum was significantly higher in women with the fibrocystic subtype of FCC (P<0.001) than in healthy women. No correlations between the blood serum concentrations of HA and of EGF were found in either the control group or the study group. The significantly higher blood serum concentrations of HA and EGF women with FCCs than in healthy women suggest that HA and EGF have a role in the development of this disease.

Topics: Adult; Biomarkers; Biopsy, Needle; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Female; Fibrocystic Breast Disease; Histamine; Humans; Middle Aged; Probability; Prognosis; Reference Values; Sensitivity and Specificity

In breast cyst fluid obtained from 50 patients age (47.1 +/- 2.3) sodium, potassium, oestrone (E1), oestradiol (E2) androgens, progesterone, (P) and Epidermal Growth Factor--EGF were determined. Markedly higher oestrogens, progesterone, testosterone, and EGF-levels were detected in cyst fluid than in blood. These data have confirmed previous results and have clearly shown that breast cyst fluid with high potassium (ratio K/Na > 1.0) contains more oestrogens, progesterone, testosterone, androstenedione and EGF than the group with low electrolyte ratio. This finding might be put in correlation with the fact that patients with high ratio K/Na may a higher risk of breast cancer than those with low electrolyte ratio.

Topics: Adult; Androstenedione; Biomarkers; Epidermal Growth Factor; Estrogens; Exudates and Transudates; Female; Fibrocystic Breast Disease; Humans; Middle Aged; Potassium; Progesterone; Risk Factors; Sodium; Testosterone

Women affected by gross cystic disease of the breast have an increased risk of breast cancer. We report here the incidence of breast cancer by cyst type and intracystic epidermal growth factor (EGF) concentration. Our retrospective study included 504 women who had at least 1 cyst aspiration between 1985 and 1993. Cyst fluids were processed for electrolyte concentration (n = 378), EGF concentration (n = 347) or both (n = 337). Age-standardized incidence ratios (SIRs) were estimated using the population of the Genoa Cancer Registry. A multivariate Poisson regression model was used to estimate relative risks (RRs) when the study groups were compared directly. By June 1999, 19 invasive breast cancers had developed in the cohort of women. The age SIR of breast cancer calculated for the whole cohort was 3.32 (95% confidence interval 2.00-5.18). The ratio was not affected by age and was only moderately increased in women with a positive family history of breast cancer and type I cysts (i.e., those with a Na+/K+ ratio <3). However, it was significantly increased in women with high EGF concentrations. Direct comparisons confirmed that age, cyst type and family history only moderately increased the RR, whereas EGF concentration was a strong predictor of risk. Our results confirm that women affected by palpable cysts have an increased risk of developing breast cancer and suggest that the risk is higher in women with high intracystic EGF concentrations.

Topics: Adult; Age Factors; Aged; Biomarkers; Breast Neoplasms; Epidermal Growth Factor; Exudates and Transudates; Female; Fibrocystic Breast Disease; Humans; Incidence; Middle Aged; Multivariate Analysis; Regression Analysis; Retrospective Studies; Risk; ROC Curve; Sensitivity and Specificity

Estrogen-induced growth stimulation has not previously been demonstrated in estrogen receptor (ER) cDNA transfected human cell lines in contrast to breast cancer cell lines expressing endogenous ER. On the contrary, estrogen usually inhibits cell growth of ER transfected cell lines. Growth inhibition by estrogen has also been demonstrated in our cell line, F9, which is an ER transfected subline of HMT-3522 breast epithelial cells derived from fibrocystic disease and propagated in chemically defined medium. By omitting EGF in the medium, we have demonstrated not only an increased transcriptional activity of the ER but also--after an adaptation period--estrogen-dependent growth of the cells, and we have succeeded in establishing a new subline, S3B, that requires 17beta-estradiol (E2) for growth. This is the first example of a nonmalignant, human breast epithelial cell line which is dependent on estrogen for continued growth. The S3B cells express functional ER as measured by transcriptional activity. ER-E2 induced transcription was not inhibited by EGF as in F9 cells. We propose that a growth-stimulatory response of breast epithelial cells in vitro to E2 is dependent on an inactive or down-regulated EGF receptor signaling pathway and it is possible that the effect of estrogen on normal breast epithelium in vivo also is modulated by the EGFR.

Topics: Breast; Cell Division; Cell Line, Transformed; Epidermal Growth Factor; Epithelial Cells; ErbB Receptors; Estradiol; Female; Fibrocystic Breast Disease; Flow Cytometry; Humans; Receptors, Estrogen; S Phase; Signal Transduction; Transcription, Genetic; Transfection

The intracystic electrolyte content is generally used to identify different breast cyst subpopulations: cysts containing high K+ levels have been associated with an increased risk of subsequent breast cancer. In order to define whether other biochemical features of breast cyst fluid (BCF) might further explain such an increased risk, we determined the content of epidermal growth factor (EGF), a known mitogenic factor for normal and transformed breast epithelium, in cysts of women with breast cancer or proliferative lesions of the breast (atypical ductal or lobular hyperplasia and proliferative disease without atypia). Median intracystic EGF levels were significantly higher in patients with breast cancer or atypical hyperplasia than in cysts of women without any clinical or instrumental evidence of proliferative disease chosen as controls (p < 0.05 and p < 0.01, respectively). In patients affected by proliferative disease without atypia, intracystic EGF levels were not different either from controls or from the other study groups. No significant difference among groups was observed in the prevalence of Na+/K+ < 3 cysts, this being the most frequently observed type of cysts in all groups except in that with proliferative disease without atypia. No significant difference in EGF levels between cysts ipsilateral or contralateral to the biopsy was observed within each histological group. Our results indicate that EGF levels are higher in cysts aspirated from breasts with an associated proliferative pathology, either benign or neoplastic. The determination of intracystic EGF, combined with that of electrolyte content, might help to identify a subset of patients with gross cystic disease of the breast at potentially higher risk of developing breast cancer.

Topics: Adult; Aged; Aged, 80 and over; Breast; Breast Neoplasms; Case-Control Studies; Epidermal Growth Factor; Exudates and Transudates; Female; Fibrocystic Breast Disease; Humans; Middle Aged; Potassium; Sodium

We evaluated the presence and distribution of transforming growth factor-beta 1 (TGF-beta 1) in breast cyst fluid (BCF), and its relationship with intracystic epidermal growth factor (EGF). EGF and TGF-beta 1 were determined by radioimmunoassay on 47 BCFs (27 of the Na+/K+ < 3 type and 20 of the Na+/K+ > 3 type). As expected, EGF levels were inversely correlated with the Na+/K+ ratio, and were consequently higher in Na+/K+ < 3 cysts as compared with Na+/K+ > 3 cysts, (p < 0.005). By contrast, TGF-beta 1 levels were directly correlated with the Na+/K+ ratio (p < 0.01), being higher in Na+/K+ > 3 cysts, though not significantly (p = 0.057). A significant negative relationship was found between EGF and TGF-beta 1 concentration. When the analysis was performed separately in the 2 cyst sub-populations, EGF and TGF-beta 1 were found to be negatively and significantly correlated in Na+/K+ < 3 cysts only (p < 0.01). Our results demonstrate that Na+/K+ < 3 cysts contain high levels of EGF, a growth-stimulating factor, and very low levels of TGF-beta 1, a growth-inhibiting factor. This may provide an explanation for the higher risk of breast cancer observed in women with Na+/K+ < 3 cysts. Our results also suggest that EGF accumulation in this type of cysts might be regulated by TGF-beta 1.

Topics: Epidermal Growth Factor; Exudates and Transudates; Female; Fibrocystic Breast Disease; Humans; Potassium; Sodium; Transforming Growth Factor beta

Gross cystic disease is a common benign breast disease that is associated with a twofold to fourfold increase in breast cancer risk. Both diseases are hormonally induced and may share a common biochemical environment conducive to abnormal proliferative responses. A large collection of breast cyst fluid samples was analyzed for growth factors associated with cell proliferation: epidermal growth factor (EGF), insulin-like growth factor I (IGF-I), insulin-like growth factor II (IGF-II), platelet-derived growth factor (PDGF), transforming growth factor-alpha (TGF-alpha), and transforming growth factor-beta (TGF-beta). The data demonstrate that significant amounts of proliferative growth factors are present in breast cyst fluid of all cyst subtypes. The presence of IGF-II, PDGF, and TGF-beta in breast cyst fluid was confirmed for the first time. EGF, PDGF, and TGF-beta concentrations in breast cyst fluid were several times greater than reported for serum; IGF-I and IGF-II concentrations were several times lower. In the first 100 samples tested, no TGF-alpha was detected. Only EGF and IGF-II levels demonstrated a consistent correlation with apocrine type 1 cysts. These results demonstrated that effective concentrations of proliferative growth factors are in breast cyst fluid and suggest that adjacent breast tissue may be a probable source of synthesis. Growth factor profiles of breast cyst fluid may indicate the presence in breast tissue of a hormonal and proliferative environment permissive to subsequent cancer growth.

Topics: Adult; Aged; Aged, 80 and over; Epidermal Growth Factor; Female; Fibrocystic Breast Disease; Growth Substances; Humans; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Middle Aged; Platelet-Derived Growth Factor; Potassium; Sodium

Topics: Epidermal Growth Factor; Exudates and Transudates; Fibrocystic Breast Disease; Humans

The concentration of insulin-like growth factor-I (IGF-I) and its relationship to other biochemical parameters of cyst fluids was investigated in 94 cyst fluids of 86 women with gross cystic breast disease. The relationship between the biochemical parameters and the cytological features of breast fluids (presence or absence of apocrine cells) was also studied. IGF-I was detected in all tested fluids, with a concentration 50 to 100 times lower than that found in plasma. IGF-I concentration was higher in cysts with a Na+/K+ ratio greater than 3 (greater than 3) and was inversely related to both dehydroepiandrosterone sulfate (DHEA-S) and epidermal growth factor (EGF) concentration (p less than 0.001). It is suggested that Na+/K+ greater than 3 cysts have a higher permeability to plasma and extracellular fluids compared to Na+/K+ less than 3 cysts. Apocrine cells were found in 78% of Na+/K+ less than 3 fluids as well as in 53% of Na+/K+ greater than 3 fluids. A well-defined relationship was found between the biochemical parameters of breast fluids, but the presence of either IGF-I or EGF was not related to the morphology of breast cysts as assessed by cytological examination.

Topics: Biopsy, Needle; Body Fluids; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Epidermal Growth Factor; Epithelium; Female; Fibrocystic Breast Disease; Humans; Insulin-Like Growth Factor I; Metaplasia; Potassium; Precancerous Conditions; Sodium

Cathespin D (Cath D) is a proteolytic enzyme secreted by human breast cancer cells with a growth promoting activity in vitro. In the present study, we measured Cath D and Epidermal Growth Factor/alpha Transforming Growth Factor (EGF/alpha-TGF) concentrations in the breast cyst fluid (BCF) of 43 patients with gross cystic disease of the breast. Both Cath D (median 2.45 pmoles mg-1 protein; range 0-4.84 vs 0.98 pmoles mg-1 protein; range 0-3.11) and EGF/alpha-TGF (28.71 ng mg-1 protein; range 7.05-50.63 vs 10.83 ng mg-1 protein; range 0.06-30.55) levels were higher in BCF of apocrine than flattened cysts (P less than 0.0005 and P less than 0.01, respectively). Premenopausal patients showed higher concentrations of Cath D (P less than 0.05) and EGF/alpha-TGF (P less than 0.05) than postmenopausal patients. A positive correlation was obtained between intracystic concentrations of Cath D and EGF/alpha-TGF (P less than 0.00001). The higher levels of Cath-D and EGF/alpha-TGF found in apocrine cysts could provide an explanation for the increased risk of subsequent breast cancer in women with this type of cyst.

Topics: Adult; Aged; Ascitic Fluid; Cathepsin D; Epidermal Growth Factor; Female; Fibrocystic Breast Disease; Humans; Middle Aged; Transforming Growth Factor alpha

The relationship between intracystic levels of epidermal growth factor (EGF) and those of dehydroepiandrosterone sulphate (DHEA-S), delta-4-androstenedione (delta-4-A), 17-beta-estradiol (17-beta-E) and progesterone (PROG) have been studied in 77 breast cyst fluid (BCF) samples. EGF and all tested hormones appeared to be inversely correlated with the intracystic Na+/K+ ratio (p less than 0.001). Consequently, when the BCFs were subdivided according to the Na+/K+ ratio, significantly higher levels of EGF, DHEA-S, delta-4-A, 17-beta-E and PROG were found in Na+/K+ less than 3 BCFs compared with Na+/K+ greater than 3 BCFs (p less than 0.001 in all cases). Strong direct relationships were found among all steroid hormones when they were correlated to one another (p less than 0.001). Intracystic EGF concentration was directly and significantly correlated with each tested hormone (p less than 0.001). However, the relationship between EGF and steroid hormones appeared to be different in the 2 BCF types (Na+/K+ less than 3 or greater than 3).

Topics: Adult; Aged; Androgens; Epidermal Growth Factor; Estradiol; Female; Fibrocystic Breast Disease; Humans; Middle Aged; Potassium; Progesterone; Sodium

Topics: Adult; Epidermal Growth Factor; Estradiol; Female; Fibrocystic Breast Disease; Humans; Middle Aged; Potassium; Sex Hormone-Binding Globulin; Sodium

Topics: Biopsy, Needle; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Epidermal Growth Factor; Epithelium; Exudates and Transudates; Female; Fibrocystic Breast Disease; Humans; Potassium

Topics: Adult; Chlorine; Electrolytes; Epidermal Growth Factor; Exudates and Transudates; Female; Fibrocystic Breast Disease; Humans; Insulin-Like Growth Factor I; Middle Aged; Potassium; Sodium; Somatomedins

Gross cystic breast disease is a common condition in women. Women with apocrine breast cysts (breast cyst fluid Na+/K+ less than 3) may be at higher risk of breast cancer than women who have cysts lined by flattened epithelium (Na+/K+ greater than or equal to 3). Breast cyst fluid concentrations of epidermal growth factor were significantly higher in the low electrolyte ratio group than in the high electrolyte ratio group (356.2 ng/ml vs 104.1 ng/ml, P less than 0.0003). A negative correlation was obtained between intracystic epidermal growth factor concentrations and Na+/K+ (rs = -0.666, P less than 0.001). No significant difference was found between the total oestradiol concentrations in the two cyst groups. However, the unbound oestradiol concentrations on a limited number of samples were significantly higher in the low electrolyte ratio group than in the high electrolyte ratio group (P less than 0.05). The higher concentrations of EGF in cyst fluid with Na+K+ less than 3 may explain why women with apocrine breast cysts may be at increased risk of developing breast cancer.

Topics: Apocrine Glands; Epidermal Growth Factor; Epithelium; Estradiol; Exudates and Transudates; Female; Fibrocystic Breast Disease; Humans; Potassium; Sodium

Women with palpable breast cysts which are lined with apocrine epithelium may be at higher risk of developing breast cancer than women with breast cysts which are lined with flattened epithelium, the former group being characterized by intracystic sodium to potassium ratios below 3, while the latter group has intracystic sodium to potassium ratios above 3. In this study the distribution of intracystic concentrations of the mitogenic peptides, epidermal growth factor, endothelin and gastrin-releasing peptide in the 2 groups of breast cysts were compared to see whether differences in concentrations between the 2 cyst groups might provide an explanation for the higher risk of breast cancer observed in women with "apocrine" breast cysts. The concentrations of epidermal growth factor and gastrin-releasing peptide were significantly higher in the low electrolyte ratio group (p less than 0.001). There was no difference in endothelin concentrations between the 2 groups. Negative correlations were found between epidermal growth factor concentrations and Na+/K+ and between gastrin-releasing peptide concentrations and Na+/K+ (p less than 0.001). A positive correlation was found between gastrin-releasing peptide and epidermal growth factor concentrations in breast cyst fluid (p less than 0.001). The significantly higher intracystic concentrations of both epidermal growth factor and gastrin-releasing peptide in the low-electrolyte-ratio group may provide an explanation for the higher risk of breast cancer which has been observed in women with "apocrine" breast cysts.

Topics: Endothelins; Epidermal Growth Factor; Exudates and Transudates; Female; Fibrocystic Breast Disease; Gastrin-Releasing Peptide; Growth Substances; Humans; Peptides; Potassium; Sodium

Breast cyst fluid from 35 women was stratified into risk groups based on personal and family history of breast cancer. Mitogenic activity in breast cyst fluid of women at highest risk to develop breast cancer was significantly higher than the activity in the lowest-risk group. There was a direct dose-dependent relationship between mitogenic activity and increased risk of developing breast cancer. Size-exclusion chromatography showed that breast cyst fluid from women at highest risk contained two peaks of growth factor activity: less than 6 kilodaltons (kd), identified as human EGF (epidermal growth factor), and 6 to 18 kd. Moderate-risk group samples demonstrated only the single less than 6 kd peak, whereas the lowest-risk group had insignificant growth-promoting activity. Breast cancer tissue analyzed in a similar manner revealed a predominant 6- to 14-kd peak of mitogenic activity demonstrating the same acid- and heat-stability found in breast cyst fluid.

Topics: Biomarkers, Tumor; Breast Neoplasms; Cells, Cultured; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Epidermal Growth Factor; Female; Fibrocystic Breast Disease; Growth Substances; Humans; Mitosis; Molecular Weight; Risk Factors

Topics: Apolipoproteins; Apolipoproteins D; Biomarkers, Tumor; Breast Neoplasms; Carrier Proteins; Epidermal Growth Factor; Exudates and Transudates; Female; Fibrocystic Breast Disease; Glycoproteins; Humans; Insulin-Like Growth Factor I; Membrane Transport Proteins; Neoplasm Proteins; Prolactin; Radioimmunoassay; Tumor Cells, Cultured

Topics: Adult; Epidermal Growth Factor; Exudates and Transudates; Female; Fibrocystic Breast Disease; Humans; Insulin-Like Growth Factor I; Middle Aged; Somatomedins

Topics: Apolipoproteins; Apolipoproteins D; Biomarkers, Tumor; Carrier Proteins; Chlorides; Epidermal Growth Factor; Female; Fibrocystic Breast Disease; Glycoproteins; Humans; Immunoglobulin A, Secretory; Membrane Transport Proteins; Neoplasm Proteins; Nipples; Potassium; Pyrones; Sodium; Suction

Epidermal growth factor (EGF), dehydroepiandrosterone (DHA)-sulphate and [Na+] and [K+] were assayed in 78 cyst fluids from patients with a palpable breast cyst. Epidermal growth factor was detected in all but 2 cysts, the mean value +/- SEM being 506.2 +/- 39.3 ng/ml, with a range of 0-1,599 ng/ml. When the cyst fluids were sub-divided according to their [Na+]:[K+] ratio, group A cyst fluids ( [Na+]:[K+] less than 3) had a significantly higher (p less than 0.001) level of EGF than group B cyst fluids ([Na+]:[K+] greater than 3). Furthermore, the relationship between EGF and [Na+] and [K+] and between EGF and DHA-sulphate seemed to differ between the 2 cyst types and each cyst type was therefore analyzed separately.

Topics: Aged; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Electrolytes; Epidermal Growth Factor; Female; Fibrocystic Breast Disease; Humans; Middle Aged; Proteins; Radioimmunoassay

Gross cystic breast disease is a common condition. Women with apocrine breast cysts may be at higher risk of breast cancer than women with cysts which are lined by flattened epithelium. Apocrine cysts have been shown to be associated with higher intracystic levels of dehydroepiandrosterone sulphate and intracystic sodium to potassium ratios of less than 3. In this study we measured the concentrations of epidermal growth factor, dehydroepiandrosterone and its sulphate in breast cyst fluid. The concentrations of all three analytes were significantly higher in cysts with intracystic Na+/K+ ratios of less than 3 than in cysts with electrolyte ratios of greater than or equal to 3 (P less than 0.001). The higher levels of EGF in cysts with low intracystic electrolyte ratios may provide an explanation of why women with apocrine cysts may be at greater risk of breast cancer. Positive correlations were obtained between concentrations of EGF and DHAS and between EGF and DHA, compatible with the view that intracystic EGF levels may be androgen-modulated. A positive correlation was also obtained between DHA and DHAS concentrations which supports the view that DHA in cyst fluid may be derived from the metabolism of DHAS in the breast cyst wall.

Topics: Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Epidermal Growth Factor; Female; Fibrocystic Breast Disease; Humans

insulin-like growth factor-I (IGF-I) was measured in breast cyst fluid and serum collected at the same time. In addition, epidermal growth factor (EGF) was measured in breast cyst fluid. The radioimmunoassay inhibition curve of cystic IGF-I was parallel to that of authentic IFG-I. Cystic immunoreactive IGF-I had an elution pattern similar to IGF-I from Sep-Pak C18 silica columns and from gel-filtration chromatography using Sephacryl 200. The material from Sephacryl 200 gave a radioimmunoassay curve which was parallel to IGF-I. The median (range) amount of IGF-I in cyst fluid was 9.3 ng/ml (0.8-33.3 ng/ml) and was 5-10% of that found in serum, although there was no significant correlation between the two levels. The median (range) level of cystic EGF was 416 ng/ml (14-1640 ng/ml). There was a weak negative correlation between cystic EGF and cystic IGF-I (P less than 0.01). Some women presented with multiple cysts and for these cysts there was a high degree of concordance of levels for both IGF-I or EGF. Unlike serum there was little or no protein present in cyst fluid which bound IGF-I.

Topics: Epidermal Growth Factor; Female; Fibrocystic Breast Disease; Humans; Insulin-Like Growth Factor I; Radioimmunoassay; Somatomedins

In recent years, several studies focused on the biochemical analysis of breast cyst fluid composition. It has been shown that breast cysts lined by apocrine epithelium contain higher levels of potassium and dehydroepiandrosterone-sulphate as compared to cysts lined by flattened cells, and that women with apocrine cysts are more likely to develop breast cancer. In the present study, we measured the intracystic levels of sodium (Na+), potassium (K+), dehydroepiandrosterone-sulphate (DHEA-S), and epidermal growth factor (EGF), a factor which could play a role in the autocrine or paracrine control of breast cancer cell growth as recently proposed by some investigators. Breast cyst fluids obtained by fine-needle aspiration from 86 women with gross cystic breast disease were assayed. On the basis of the relative intracystic concentrations of Na+ and K+ two main classes of cysts were defined. An arbitrary cut-off value of 3 for the Na+/K+ ratio seemed adequate to separate these two types of cysts. An inverse relationship was found between the Na+/K+ ratio and DHEA-S concentration, median levels of the androgen conjugate being 3615 micrograms/dl in Na+/K+ less than 3 cysts and 480 micrograms/dl in Na+/K+ greater than 3 cysts (P less than 0.001). EGF levels were found to be significantly higher in Na+/K+ less than 3 cysts as compared to Na+/K+ greater than 3 cysts: 103.26 ng/ml versus 57.22 ng/ml, respectively (P less than 0.001). EGF appeared inversely correlated with total protein concentration in the Na+/K+ greater than 3 cysts, while in the Na+/K+ less than 3 cysts high EGF levels were observed independently of total protein content. In addition, a direct correlation was found between EGF and DHEA-S concentrations. On the basis of these results, the hypothesis can be made that EGF, which is measurable in all breast fluids tested and is nearly undetectable in plasma, is actually produced by the epithelium lining the cyst wall, particularly as far as the Na+/K+ less than 3 cysts are concerned. In view of our results this type of cyst, which has been shown to be lined by apocrine epithelium, appears to be characterized by high DHEA-S and EGF levels. It is suggested that the latter finding could provide a clue for understanding the increased risk of subsequent breast cancer in women bearing apocrine cysts.

Topics: Adult; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Epidermal Growth Factor; Exudates and Transudates; Female; Fibrocystic Breast Disease; Humans; Menopause; Middle Aged; Potassium; Proteins; Sodium

The frequency of gross cystic breast disease in premenopausal women and its possible association with increased breast cancer risk emphasize the importance of investigations relating to breast cyst fluid composition. In order to contribute to a better analysis of this medium, we have measured four proteins the presence of which in human milk was well documented. Breast cyst fluid specimens from 266 breast cyst disease patients were assayed and compared as to concentrations of alpha-lactalbumin, gross cystic disease fluid protein (GCDFP-15), epidermal growth factor (EGF), and epithelial membrane antigen (EMA). All the analyzed cyst fluids contained GCDFP-15, EMA, and EGF whereas alpha-lactalbumin was detected in only 14.2% of fluids assayed. Positive correlations were observed between GCDFP-15 and EMA concentrations (P less than 0.005), as well as GCDFP-15 and EGF concentrations (P less than 0.0005). The cyst fluid GCDFP-15 and EGF levels were higher when alpha-lactalbumin concentrations were below detection limits. This association was statistically significant for GCDFP-15 (P less than 0.03) and for EGF (P less than 0.001). These results suggest that GCDFP-15 and EMA could be the biochemical expression of apocrine metaplasia and epithelial hyperplasia, respectively, two histopathological features which characterize breast cystic disease. On the other hand, the occasional presence of alpha-lactalbumin in the cyst fluid would reflect the persistence of differentiated cells in the epithelium surrounding the cyst and would be inversely proportional to the degree of cellular proliferation. The omnipresence of EGF in the cyst fluid argues for the hypothesis of its production by the mammary gland. The highly significant relationship between GCDFP-15 and EGF levels in the medium remains to be elucidated but may be related to an androgen sensitivity in the breast epithelium surrounding the cyst.

Topics: Apolipoproteins; Apolipoproteins D; Body Fluids; Carrier Proteins; Epidermal Growth Factor; Female; Fibrocystic Breast Disease; Glycoproteins; Humans; Immunoassay; Lactalbumin; Membrane Proteins; Membrane Transport Proteins; Mucin-1