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- The aim of the study was to assess the role of the estradiol and progesterone relationship during the late luteal phase and the occurrence of fibrocystic breast disease (FBD). The concentration of estradiol/progesterone was measured in the group of women with FBD as study group (n=50) and control group of women without FBD (n=40). All women had regular ovulation cycles. Blood samples for estradiol (E2), progesterone (P) and prolactin determination were obtained in the morning at 8 am on days 21 and 24 of menstrual cycle. Significant mastalgia and mastodynia history in women with FBD was obtained with yes or no questionnaire. FBD diagnosis was confirmed with ultrasound (size and number of simple cysts). In the control group, a reduced E2/P ratio was noticed from day 21 to day 24 of the cycle (from 14.8±11.5 pg/mL to 9.1±6.1 pg/mL; p<0.05), which was not recorded in the group of women with FBD (study group). Even the slightest disturbance of the E2/P ratio may contribute to the occurrence of FBD with clinical manifestations of mastalgia and mastodynia.

Background: Reduction in the level of tissue decorin is a hallmark of many types of cancer including breast carcinoma. However, reduced decorin expression has also been reported in several types of benign tumors to the extent that it has been proposed as a tissue marker to differentiate malignant from benign tumors. The aim of this study was to investigate the potential role of plasma decorin to distinguish breast cancer from fibroadenoma, the second most common type of benign tumor, after fibrocystic disease., Methods: From 35 patients recruited in this study, 24 were affected with invasive ductal carcinoma, either grade II (n = 14) or grade III (n = 10). The other 11 patients had fibroadenoma lesions in their breasts. Tissue decorin mRNA and protein levels were assessed with real-time qPCR and Immunohistochemical analysis. ELISA was employed to measure plasma levels of decorin., Results: The mean plasma decorin in cancer patients was measured to be 5.42 ± 1.83 ng/mL while fibroadenoma patients had an average of 4.22 ± 1.17 ng/mL decorin in their plasma. The difference was not significant. However, the mean expression level of decorin mRNA calculated by the 2-ΔΔCt method was 5.6-fold lower in the biopsied tissue specimens of IDC patients versus fibroadenoma, as expected. Consistent reduction in protein abundance was observed in the studied tissue sections., Conclusion: We have shown that tissue decorin is a reliable marker, unaffected by patient disease stage, to differentiate IDC from fibroadenoma. However, plasma decorin does not seem to have diagnostic value in this regard., (© 2018 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Equol (a bacterial metabolite of the soy isoflavone daidzein) is produced by 30% to 50% of humans and may be associated with health outcomes. We hypothesized that plasma equol would be inversely associated with risks of fibrocystic breast conditions (FBC) and breast cancer (BC). Plasma from women in a breast self-examination trial in Shanghai with BC (n=269) or FBC (n=443), and age-matched controls (n=1027) was analyzed for isoflavones. Equol was grouped into categories (<20, 20-<45, and ≥45nmol/L) and, among women with daidzein ≥20nmol/L, the log10 equol:daidzein ratio was grouped into tertiles. Where available, non-cancerous tissue (NCT) adjacent to the carcinomas from women with BC were classified as non-proliferative or proliferative (n=130 and 172, respectively). The lesions from women with FBC were similarly classified (n=99 and 92, respectively). Odds ratios (OR) and 95% confidence intervals (CI) were calculated across equol categories and tertiles of log10 equol:daidzein ratio. Equol categories were not associated with FBC or BC (P>.05). For log10 equol:daidzein, compared to controls there were positive associations in the mid tertile for proliferative FBC (OR 2.06, 95% CI 1.08-3.93), BC with proliferative NCT (OR 2.95, 95% CI 1.37-6.35), and all BC regardless of histology (OR 2.37, 95% CI 1.43-3.95). However, trends in ORs with increasing plasma equol values or equol:daidzein ratios were not observed (P>.05). The results of this study do not provide evidence that equol plays a role in the etiology of these breast conditions. However, further work is needed to confirm or refute this conclusion., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Obesity is a risk factor for breast cancer in postmenopausal women. Leptin, a hormone excessively produced during obesity, is suggested to be involved in breast cancer. The aim of the study was to investigate procarcinogenic potential of leptin by evaluating influence of leptin on cell proliferation, cell cycle, apoptosis, and signaling on numerous breast cells lines, including 184B5 normal cells, MCF10A fibrocystic cells and MCF-7, MDA-MB-231, and T47D cancer cells. Expressions of leptin and Ob-R were analyzed using qRT-PCR and immunohistochemistry, proliferation using fluorimetric resazurin reduction test and xCELLigence system, apoptosis and cell cycle by flow cytometry, and effect of leptin on different signalling pathways using qRT-PCR and Western blot. Cells were exposed to increasing concentrations of leptin. All cell lines expressed mRNA and protein of leptin and Ob-R. Leptin stimulated proliferation of all cell lines except for 184B5 and MDA-MB-231 cells. Leptin inhibited apoptosis but didn't alter proportion of cells within cell cycle in MCF7 cells. Leptin induced overexpression of leptin, Ob-R, estrogen receptor, and aromatase mRNA in MCF-7 and T47D cells. Autoregulation induced by leptin, relationship with estrogen pathway, and proliferative and antiapoptic activity in breast cancer cells may explain that obesity-associated hyperleptinemia may be a breast cancer risk factor.

Background: The true association between breast cancer and vitamin D is currently under investigation. We compared serum 25-hydroxy-vitamin D levels in women with benign and malignant breast masses and controls., Materials and Methods: Levels of vitamin D were measured by electrochemiluminescense. Serum levels >35 ng/ml, 25-35 ng/ml, 12.5-25 ng/ml and <12.5 ng/ml were considered as normal, mild, moderate and severe vitamin D deficiency, respectively., Results: Overall, 364 women were included in the control, 172 in the benign and 136 in the malignant groups. The median serum vitamin D level was significantly lower in breast cancers than controls. Levels were also lower in malignant than benign cases and in benign cases than controls although statistically non-significant., Conclusions: Multinomial logistic regression analysis showed that severe vitamin D deficiency causes a three-fold increase in the risk of breast cancer while this was not the case for moderate and mild deficiency.

Background: Fibrocystic breast disease is one of the most frequent conditions of the breast among women from 30 to 49 years, with a frequency of about 60%, hence the interest in studying and treating it with the most advanced and effective resources., Objective: To compare the efficacy and adverse events of alpha dihydroergocryptine with cabergoline in patients with fibrocystic breast disease., Material and Methods: A prospective, longitudinal, open, comparative study between alpha-dihydroergocryptine and cabergoline, made in the service of Gynecology and Obstetrics at the Dr. Miguel Silva General Hospital in Morelia, Michoacán. 171 patients diagnosed with fibrocystic breast disease were randomly assigned to the alpha-dihydroergocryptine or the cabergoline group. Assessments were made at baseline and every month subsequently. The following symptoms were evaluated: breast tenderness, breast pain, lumps and nipple discharge. The concentrations of prolactin were determined and an ultrasound was performed at baseline and at 3 and 6 months, patients were questioned about adverse events., Results: 171 patients were included (81treated with alpha-dihydroergocryptine and 90 with cabergoline); 156 completed the study. The age limits were 18 and 51 years. The evolution time prior to study entry was 17.71 +/- 18.3 months for the alpha-dihydroergocryptine group and 18.57 +/- 20.35 for the cabergoline group. 15 patients discontinued treatment due to adverse events (8 of the alpha-dihydroergocryptine group and 7 of the cabergoline group). The most common adverse event was headache., Conclusions: In this study alpha-dihydroergocryptine was better tolerated and had better clinical response compared with cabergoline; breast pain and breast tenderness disappeared within the first month of treatment. Adverse events were similar for both treatments.

Gross cystic disease (GCDB) is a breast benign condition predisposing to breast cancer. Cryopreserved sera from GCDB patients, some of whom later developed a cancer (cases), were studied to identify potential risk markers. A MALDI-TOF mass spectrometry analysis found several complement C3f fragments having a significant increased abundance in cases compared to controls. After multivariate analysis, the full-length form of C3f maintained a predictive value of breast cancer risk. Higher levels of C3f in the serum of women affected by a benign condition like GCDB thus appears to be correlated to the development of breast cancer even 20 years later., Biological Significance: Increased complement system activation has been found in the sera of women affected by GCDB who developed a breast cancer, even twenty or more years later. C3f may predict an increased breast cancer risk in the healthy population and in women affected by predisposing conditions., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The aim of this study is to evaluate the fibrocystic breast disease rates and its association with different clinical, endocrine and metabolic parameters between main polycystic ovary syndrome (PCOS) phenotypes. One hundred thirty two consecutive women were included in the study. Body mass index, serum follicle-stimulating hormone, luteinizing hormone (LH), progesterone, estradiol, testosterone, dehydroepiandrosterone sulphate, fasting glucose, low density lipoprotein (LDL-C), total cholesterol, high density lipoprotein, insulin, insulin sensitivity and fibrocystic breast disease rates were compared among different phenotypes of PCOS. Group 1: Polycystic ovaries (PCO)-anovulation (n = 32), Group 2: Hyperandrogenemia (HA)-anovulation (n = 28), Group 3: HA-PCO (n = 29), Group 4: HA-PCO-anovulation (n = 43). There were statistically significant differences between the different phenotype groups in terms of waist-hip ratio (p = 0.006), serum LDL-C (p = 0.008), LH (p = 0.002), estradiol (p = 0.022), fasting glucose (p = 0.001), progesterone (p = 0.007), free testosterone levels (p < 0.001) and Ferriman-Gallwey (FG) scores (p < 0.001). Different phenotype groups had significantly different fibrocystic breast disease rates. (p = 0.016). Higher free testosterone >3 pg/dl was protective for fibrocystic disease (RR = 0.316, 95:% CI 0.109-0.912, p = 0.033). Higher FG scores were more protective for fibrocystic disease (RR = 0.005, 95:% CI 0.001-0.042, p < 0.001). Group 3 ovulatory PCOS patients with PCO and hyperandrogenemia phenotype had lower risk to develop fibrocystic disease, while higher rates were observed in group 1 anovulatory-normoandrogenemic PCOS patients. Hyperandrogenemia is protective for fibrocystic diseases in PCOS.

Benign breast lesion is an important risk factor for breast cancer and elevated CA-15.3 in serum is a well established marker of breast cancer. Core-needle biopsy is now the method of choice to sample non-palpable mammographic abnormality and as well as clinically palpable lesion. To asses relationship of serum CA-15.3 with different histologic entities of benign breast lesion and usefulness of this marker in predicting breast cancer in this high risk group, a study was conducted among 140 patients who had a diagnosis of benign breast lesion and malignancy following fine needle aspiration cytology (FNAC) at department of surgery, Medical College, Kolkata between 2007 and 2009. We prospectively estimated serum CA-15.3 level in all patients. Different histologic entities of benign breast lesion, who showed serum CA-15.3 level >30U/ml underwent tru-cut biopsy to detect malignancy. Of 140 patients studied, 50 were stamped as malignancy and 90 as benign after FNAC of which 20 patients had fibroadenoma, 25 had fibro-adenoma with fibrocystic disease, 20 had fibrocystic disease with epitheliosis and 25 had fibrocystic disease with atypia. All breast cancer patients and 10 each from fibro-adenoma with fibrocystic disease, fibrocystic disease with epitheliosis and fibrocystic disease with atypia had serum CA -15.3 level>30U/ml. Thirty patients with benign breast lesion who had raised CA-15.3 underwent core-needle biopsy. Fifteen patients were detected to have intraductal carcinoma, mostly with fibrocystic disease with atypia. Clinical applicability of serum CA-15.3 to detect breast cancer should be strongly considered in management of patients with benign breast lesion and tru-cut biopsy than FNAC be done before benign breast lesion being stamped as benign. Biopsy results that are not concordant with the targeted lesion require surgical biopsy.

Various retinoic acid (RA) isomers (all-trans, 13-cis, 11-cis, and 9-cis) as well as retinol, carotenoids, and tocopherol concentrations were determined in both serum and breast adipose tissue of 22 benign breast disease patients and 52 breast cancer patients categorized into 4 stages by malignancy. Serum RA isomers were analyzed by a newly developed sensitive method combining a high-performance liquid chromatography and a gas chromatography-mass spectrometry, and retinol, carotenoid, and tocopherol concentrations using a high-performance liquid chromatography system. The breast cancer patients showed significantly lower serum retinol, whereas significantly higher breast adipose tissue retinol concentration than those of benign breast disease patients. Although breast cancer patients showed significantly higher serum all-trans and 13-cis RA concentrations, 11-cis RA in breast adipose tissue was significantly lower in the breast cancer patients than those of benign breast disease patients and it was associated with the stage of malignancy. The current study indicates that the retinol and RA isomers in the target tissue of breast tumor patients are not reflecting their concentrations in circulation. The mechanisms of tissue specific uptake of RA isomers and their functions warrant further studies.

The paper presents the results of an association study of a predisposition to increased somatic mutagenesis detected by the test for TCR-mutant lymphocytes (CD3-CD4+ phenotype). A study group consisted of 251 women who lived in the towns polluted by radionuclides after the Chernobyl accident and had estrogen-dependent reproductive system diseases (uterine myoma, fibrocystic mastopathy). The carriage of minor alleles in the genes (CYP1A1, GSTM1, and ABCB1) of all three stages of detoxification of xenobiotics was associated with the rise in the spontaneous frequency of TCR-mutant cells. Overweight modified the genotype (at CYP1A1 and GSTT1 loci) - environment interaction. When background radiation became higher, the contribution of minor alleles in the CYP1A1 genes to the instability recorded as the elevated frequency of TCR-mutant cells increased.

PSA-prostate specific antigen is considered to be a useful marker in the diagnosis and monitoring of prostate cancer Currently PSA was also detected in serum and tissues of women. We reviewed the literature dealing with the existence and role of this marker in women.

Objective: The aim of the study was to evaluate the relationship between serum free and total PSA and histopathological findings in women with fibrocystic mastopathy., Material and Methods: 176 women with fibrocystic breast disease, aged 18 to 45 years.--Group I: comprised 114 patients with cysts < 10 mm in diameter--group II: comprised 62 women with cysts > 10 mm in diameter. The control group consisted of 46 healthy women aged 18 - 45 years who had no breast pathology Total PSA (PSA-T) and free PSA (PSA-Free) were measured by an ultra-sensitive fluoroimmunometric DELFIA assay (Prostatus PSA Free/Total Wallac, Turku, Finland). The detection limit for PSA was 0.01 ng/ml. Endometrial samples have been obtained with Pipelle probe between 22 and 24 days of the menstrual cycle., Results: In the control group secretory endometrium was more frequently detected than in the mastopathy group (chi2 = 11,15, p = 0.01). Proliferatory (chi2 = 8.27, p = 0.004) and presecretory endometrium (chi2 = 4.61, p = 0.03) were more frequently detected in the mastopathy group than in controls. We did not find statistically significant relationship between the mean PSA concentrations between the groups in relation to histopathological findings., Conclusions: No relationships between free and total PSA measured in the follicular phase of the menstrual cycle and endometrial findings were detected in our study. Further research is required to evaluate the relationship between PSA and endometrial findings.

Background: Hepatocyte growth factor (HGF) also known as scatter factor (SF) and its receptor c-met play important roles in mammary differentiation and have been implicated in mammary carcinogenesis., Objective: Estimation of the plasma level of HGF in females with benign breast lumps or breast carcinomas and correlating levels with important prognostic parameters., Subjects: Sixty eight adult premenopausal females were divided into control group of fifteen healthy volunteers and fifty-three patients subdivided into fifteen with benign breast lumps and thirty-eight with breast carcinomas., Methods: A thorough clinical examination, plain chest x-rays, ultrasonography of the abdomen and pelvis, pre- operative fine needle aspiration cytology, estimation of fasting serum glucose, urea, creatinine and uric acid levels, alanine aminotransferase activities, C-reactive protein, HGF level and histopathological examination of the breast masses were performed., Results: Significant increase in HGF levels was found in patients with benign breast lumps and in breast cancer patients when each was compared to controls and when cancer patients were compared to the benign breast lumps group., Conclusion: The serum level of HGF is an independent prognostic indicator for breast cancer.

The objective of this study was to evaluate serum prostate specific antigen (PSA) levels in women with menstrual disturbances and fibrocystic mastopathy. A total of 114 women with fibrocystic breast disease with cysts <10 mm (group I), 62 with macrocysts >10 mm (group II) and 46 healthy volunteers, who served as control subjects, were recruited for this prospective study. Each patient underwent complete gynecological examination and had performed sonography of the breasts. Moreover menstrual pattern, serum levels of free and total PSA, LH, FSH, SHBG, PRL, estradiol, progesterone, TSH, T4, as well as serum total testosterone, were evaluated in each subject. We compared serum free and total PSA levels between women with different menstrual pattern within groups of women with micro- and macrocysts. We also evaluated correlations between serum free and total PSA and hormonal/descriptive variables. We found that, in group II, women with regular menses and polymenorrhea revealed significantly higher serum free PSA than women with oligomenorrhea and secondary amenorrhea. Moreover, we found a positive correlation between serum total testosterone and total PSA in the control group and between progesterone and total PSA in group II. Our data show that serum free PSA is increased in women with regular menstrual cycles and polymenorrhea. This later relationship refers to women with macrocysts. Further studies are required to clarify the relationships between serum PSA and menstrual disturbances in women with mastopathy.

Background: Although benign breast changes are more common than breast cancer, little evidence regarding risk factors for benign breast conditions is available. Omega-3 (n-3) fatty acids have antiinflammatory and antiproliferative actions and may be important in reducing the risk of benign conditions. There is a lack of research on the association of n-3 fatty acids with risk of benign fibrocystic breast changes., Objectives: The objectives of the study were to evaluate the role of n-3 and other fatty acids in the development of benign proliferative fibrocystic conditions (PFCs) and nonproliferative fibrocystic conditions (NPFCs) in the breast and to evaluate the progression of fibrocystic changes in breast cancer., Design: We conducted a case-control study to determine erythrocyte fatty acid concentrations in 155 women with NPFCs, 185 women with PFCs, 241 women with breast cancer (127 with nonproliferative and 114 with proliferative changes in the noncancerous extratumoral mammary epithelium), and 1,030 control subjects. We estimated the relative risk of NPFCs, PFCs, and breast cancer with proliferative and nonproliferative changes in extratumoral tissue compared with the risk of these changes alone., Results: Women in the highest quartile of eicosapentaenoic acid concentrations were 67% less likely to have an NPFC alone or with breast cancer and 49% less likely to have breast cancer than were women with PFCs. gamma-Linolenic acid (18:3n-6) was positively associated with all fibrocystic and cancerous conditions. Palmitic:palmitoleic acid (n-7 saturation index) was inversely associated with risk in all comparisons., Conclusion: Our results support a protective effects of n-3 fatty acid intake and the n-7 saturation index against benign fibrocystic breast changes and the progression of proliferative changes to breast cancer.

Unlabelled: Lipid metabolism disorders--breast cancer risk association in postmenopausal women was searched in many studies; the HDL-cholesterol value triggered most of controversies. Some authors plead for increased breast cancer risk in overweight/obese postmenopausal women if HDL is higher while others plead for higher risk if HDL is lower then in general population., Material and Method: We studied a 110 subjects female population aged between 41 and 69, and determined height, weight, body mass index (BMI), abdominal perimeter (AP), lipid parameters (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides). All women performed mammography and breast echography. Imagery divided the subjects in three groups: 30 breast cancer patients (first diagnosis)--group 1, 50 breast dysplasia women--group 2, and normal breast patients--group 3., Results: HDL-cholesterol proved significantly higher in group 2 compared to group 3 (control group), by the third and the fourth quartile; the same when it came to overweight/obese post-menopausal women. Nevertheless, more lipid disorders clustered in group 1 obese/overweight postmenopausal women., Conclusions: High HDL in breast dysplasia women is reported in international studies too. High menopause prevalence in group 3, implying abdominal obesity and lipid disorders may explain the small difference between group 1 (breast cancer patients) and group 3 (control group). High clustering in group 1 pleads for increased breast cancer risk in metabolic syndrome postmenopausal women. Comparing HDL values and the clustering phenomenon in group 1 to the other two groups considered as a control population (as done in international published studies), we can conclude that low HDL--abdominal obesity association increases breast cancer risk after the menopausal age.

Objectives: Fibrocystic mastopathy is the most common benign breast disease. Available evidence suggests that the presence of breast cysts increases the risk of breast cancer. The purpose of the study was to evaluate and compare the detection rate of total and free prostate-specific antigen (PSA) in the serum samples of healthy women and in those of women with cystic mastopathy. Moreover, we compared PSA concentrations in the serum samples of the study groups., Study Design: The study population included 114 women with fibrocystic breast disease, with cysts measuring <10mm (Group I) and 62 with macrocysts measuring >10 mm (Group II). Forty-six healthy volunteers were enrolled in the study as a control group. We analyzed the frequency of the detection level and the mean serum concentrations of total and free PSA in women with mastopathy and in healthy participants. Total PSA (PSA-T) and free PSA (PSA-Free) were measured by an ultrasensitive fluoroimmunometric DELFIA assay (Prostatus PSA Free/Total Wallac, Turku, Finland). The detection limits was 0.01 ng/ml., Results: Our results showed the statistical significance of the fact that the detection rate of free and total PSA was higher in all women with mastopathy (Group I with II) than it was in the control group. There were no differences between Group I and Group II regarding the detection rate of the two forms of antigen and between the control group and Group II in the detection rate of total PSA. We also demonstrated that the mean concentration levels of both free and total PSA were significantly higher in the serum of women with mastopathy than in the control group., Conclusion: These findings suggest that women with mastopathy, regardless of the size of the cysts, produce and release more PSA into the serum than women without breast pathology. The PSA may be a new marker for the assessment of benign breast disease.

Background: Proliferative benign breast conditions are associated with elevated risk of breast cancer, whereas nonproliferative conditions are not strongly associated with risk. Factors acting before onset of hyperplasia might be associated with both benign conditions and breast cancer, whereas those on the proliferative disease-to-cancer pathway would be associated only with cancer. Soy isoflavone exposure may influence breast cancer risk, but little is known of its association with benign conditions., Materials and Methods: We examined possible relationships between plasma genistein and daidzein concentrations and risk of breast disease in women, in a breast self-examination trial in Shanghai, China, diagnosed with breast cancer (n = 196) or a benign breast condition (n = 304), and 1,002 age-matched controls with no known breast disease. Benign conditions were classified as nonproliferative (n = 131) or proliferative with or without atypia (n = 173)., Results: Isoflavone concentrations were inversely associated with risk of nonproliferative and proliferative benign fibrocystic conditions, as well as with breast cancer, both with and without concomitant proliferative changes in ipsilateral noncancerous mammary epithelium (P(trend) < 0.01 for all comparisons with controls). Women in the highest quartile of plasma genistein (>76.95 ng/mL) were less likely to have breast cancer (odds ratio, 0.26; 95% confidence interval, 0.13-0.50) or benign conditions (odds ratio, 0.40; 95% confidence interval, 0.23-0.70) compared with women in the lowest quartile (<9.42 ng/mL). Observed risks for breast cancer with and without surrounding proliferative changes were not different, respectively, from observed risks for benign proliferative and nonproliferative conditions alone., Conclusion: Isoflavone exposure was inversely associated with fibrocystic breast conditions and breast cancer, and the results suggest that effects on cancer risk occur early in carcinogenesis.

A prospective clinical parametric study comprising women afflicted by breast cancer and otherwise healthy participants was undertaken. The mean plasmatic concentration of putative leucine amino peptidase and nucleoside diphosphate phosphotransferase enzymatic complex in breast cancer cases was significantly elevated [43.9 +/- 2.8 microg ml(-1) (n = 9)] when compared to those found in otherwise healthy women [8.07 +/- 0.14 microg ml(-1) (n = 8)]. Women without images compatible with any tumours (n = 13) had a mean concentration of 10.77 +/- 1.49 microg ml(-1). The mean value obtained in women with fibroadenomas was 10.15 +/- 0.81 microg ml(-1) (n = 6) and with cystic fibrosis mastopathy 8.75 +/- 0.28 microg ml(-1) (n = 7). The efficacy of a tandem quantitative biodiagnostic system as a parametric screening tool for the early detection of breast cancer is underlined, raising the possibility of increasing the cost effectiveness of current imaging non-parametric technologies.

Low levels of lignans, namely enterolactone, have been reported to be associated with an increased risk of breast cancer in the general female population. We assessed, retrospectively, the relationship between serum enterolactone concentrations and the occurrence of breast cancer in women with palpable cysts. The levels of enterolactone in cryopreserved serum aliquots, obtained from 383 women with palpable cysts at the time of their first cyst aspiration, were measured using a time-resolved fluoroimmunoassay (TR-FIA). After a median follow-up time of 6.5 years (range 0.5-12.75 years), 18 women were found to have developed an invasive breast cancer. Median values of serum enterolactone were significantly lower in women who subsequently developed breast cancer: 8.5 nM/l versus 16.0 nM/l: P=0.04. Odd Ratios (OR) for breast cancer were: 0.36 (P=0.03), 0.57 (P=0.3) and 0.38 (P=0.25) for 25th (8 nM/l), 50th (16 nM/l) and 75th (24 nM/l) percentile values, respectively. The receiver operating characteristic (ROC) analysis showed a satisfactory accuracy for enterolactone as a breast cancer risk indicator (area under the curve (AUC)=0.64: P=0.04). Logistic regression analysis confirmed that the enterolactone concentration had a strong protective effect on the breast cancer risk. These findings may have important clinical implications with regard to interventional diet-focused chemo-preventive trials.

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.

Objectives: Increased estrogen activity and prolactin hypersecretion is a hormonal reason for Benign Breast Diseases., Design: To evaluate hormonal disorders in women with gross breast cysts., Material and Methods: 30 women with gross breast cysts (over 10 mm in diameter) have been investigated. Cytohormonal vaginal swabs and serum levels of prolactin, estradiol and gonadotropins were evaluated., Results: Normal prolactin levels were found in 96.7% of cases, but in 8 women with recurrent breast cysts after repeated FNA-biopsies prolactin secretion stimulated by metoclopramide was significantly increased. Low progesterone activity in all women and low estrogen activity in 65.3% were shown. Absolute high estrogen activity was diagnosed only in 8.7% women with gross breast cysts., Conclusions: Nearly all patients with gross breast cysts have normal prolactin and low progesterone levels. High estrogen levels appear very seldom and in most cases these patients are hypoestrogenic.

Objective and Study Design: To evaluate the concentrations of prolactin and estrogens in blood sera in women with fibrocystic changes in the breast (FCC)., Material and Methods: The control group consisted of 32 women without any pathological changes in the breast (mean age 44.9 +/- 4.4 y.). The studied group comprised 81 women having FCC (mean age 45.5 +/- 3.5 y.). Both groups were divided into two subgroups according to age: the first subgroup ranged 40-44 y. and the second 45-51 y. The hormonal profiles, namely: prolactin in basal conditions (PRL I), and after metoclopramide-test (PRL II), follitropin (FSH), lutropin (LH), estradiol (E2), progesterone (P) were assayed by means of "bioMerioux" kits. Estrone (E1) was assayed by means of "DBC Diagnostic kits., Results: In both subgroups of the study group (40-44 and 45-51 y.) a significantly higher (p < 0.001) concentration of prolactin was shown after metoclopramide test, as well as significantly higher percentage increase in prolactin after metoclopramide test (p < 0.001) were shown in comparison with the control group. In age compartment of 40-44 y. in the study group significantly lower (p < 0.05), progesterone-estradiol index (PEL) was found in comparison with the control group. In age compartment of 45-51 y. a progesterone-estradiol index (PEL) in study group was significantly lower (p < 0.05) in comparison with the control group., Conclusion: Functional hyperprolactinemia and relative hyperestrogenism are risk factors of the development concerning fibrocystic changes in the breast.

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.

The efficacy of CEA and CA15-3 tumor markers in monitoring breast cancer was evaluated in 1365 patients with either benign (n = 534) or malignant (n = 831) breast diseases. Thirty-nine breast cancer patients were monitored before and after neoadjuvant chemotherapy. Three hundred forty-nine patients were monitored during post-surgical follow-up for either a minimum of 5 years or until time of recurrence. Twenty-one patients with metastases were also monitored during chemotherapy. Elevated CA 15-3 and TPS levels were found in 28.6% and 30.0% of patients. CA 15-3 and TPS sensitivities rose to 71.9% and 66.3% in metastatic patients, respectively. The addition of TPS to CA 15-3 increased the sensitivity up to 44.4% in the overall population, and to 87.6% in patients with metastases. During post-surgical follow-up CA 15-3 was elevated in 65.7% and TPS in 61.3% of patients with recurrence. The combination of TPS and CA 15-3 increased the overall sensitivity by 12.7%. Longitudinal monitoring of metastatic patients undergoing chemotherapy demonstrated that, when positive, both CA 15-3 and TPS paralleled response to treatment. TPS monitoring may provide additional value when used in combination with CA15-3 during post-surgical follow-up of breast cancer patients.

Measurement of serum levels of PSA is widely used as a screening tool for prostate cancer. PSA has been shown to be associated with malignancies of many other organs than prostate, including the female breast. Therefore, PSA is not prostate-specific. PSA serum levels in females increase with excess of androgens. Variable PSA expression was observed in membranes of adipocytes of fat tissue and in the endothelium of small vessels in female and male breast. There is increasing evidence that androgens play a significant role in the development and progression of breast cancer. 5alpha-reductase is an enzyme that is expressed in androgen-dependent tissues, including the female breast, catalyzing the reduction of testosterone to its more bioactive form, dihydrotestosterone, which then transactivates a number of genes. One of these genes encodes for PSA, a favorable prognostic factor in breast cancer. Interactions of PSA and sex hormones in physiological processes and in prostatic and mammary cancer have been reported. The possible influence of PSA on breast cancer growth and progression and even its physiological functions are still under controversial debate. There are some findings which might indicate similarities in the influence of steroid hormones on the development of prostate and breast malignancies, perhaps a unique hormone-dependent molecular pathway for both types of cancer., (Copyright 2001 S. Karger GmbH, Freiburg)

Objective: Angiogenin (ANG), a potent inducer of neovascularization, is secreted by some types of human tumor cells and appears crucial for their growth. This study was designed with the aim to investigate any correlation between the serum angiogenin and the clinicopathological variables and furthermore evaluate the prognostic value of serum angiogenin in patients with breast cancer., Material and Methods: Sixty-four consecutive patients with invasive breast cancer undergoing surgery were prospectively included and evaluated. Venous blood samples were collected before surgery. Sera were obtained by centrifugation and stored at -70 degrees C until assayed. The control group consisted of 16 patients with benign breast tumor (8 with fibrocystic disease and 8 with fibroadenoma). Serum concentration of angiogenin was measured by the quantitative sandwich enzyme immunoassay technique. The data on primary tumor staging, age, estrogen receptor, lymph node status, distant metastases and TNM staging were reviewed and recorded., Results: The mean value of serum angiogenin in patients with invasive breast cancer was 2123.95 +/- 324.34 pg/ml and that of control group were 2108.16 +/- 398.20 pg/ml (fibrocystic disease) and 2010.27 +/- 318.40 pg/ml (fibroadenoma). The difference was not significant (p = 0.66). Furthermore, with univariate analysis, there were no significant differences in serum angiogenin levels between the subgroups of the above-mentioned clinicopathological variables., Conclusion: Serum angiogenin levels did not appear as a meaningful prognostic parameter for invasive breast cancer.

Prostate-specific antigen (PSA) is a serine protease expressed at high levels in prostate epithelium, and elevated PSA in serum is a well-established marker of prostate cancer. Recently, the relative proportions of free PSA and PSA complexed to the serine protease inhibitor alpha 1-antichymotrypsin have become important variables in distinguishing between prostate cancer and benign prostatic hyperplasia. Numerous studies have demonstrated the production of PSA in female tissues such as the breast, and low levels of PSA are present in female sera. The objective of this study was to measure and compare the relative proportions of free PSA and PSA complexed to the serine protease inhibitor alpha 1-antichymotrypsin in the serum of women with breast cancer or benign breast disease or women with no known malignancies. PSA was measured with an established immunoassay for total PSA and a novel immunoassay for free PSA, both of which had a detection limit of 0.001 microgram/liter (1 ng/liter). The percentage of breast cancer patients with free PSA as the predominant molecular form (> 50% of total PSA) in serum was five times higher than that of healthy women or women with benign breast disease, and PSA decreased in the serum of breast cancer patients after surgery. The diagnostic use of free PSA for breast cancer is limited at this point, due to the low diagnostic sensitivity (approximately 20%); however, free PSA as the predominant molecular form shows a high diagnostic specificity (approximately 96%) in comparison to women free of breast cancer or with benign breast disease. These results suggest that the clinical applicability of free PSA for breast cancer diagnosis and the biological mechanism behind its increase should be further investigated.

Objective: To observe the therapeutic effect of Jianruling (JRL) on hyperplasia of mammary gland (HMG) and to explore its mechanism in regulating sex hormones., Methods: Clinical changes of HMG were observed and serum sex hormones measured before and after JRL treatment. In experimental study, the effect of JRL was estimated by using electron microscope, pathologic and radioimmunoassay., Results: JRL could not only cure HMG, but also regulate the sex hormone secretion both in HMG patients and in rats. Clinical study showed that the clinical cure rate was 72.5%, and the total effective rate was 90.8%, it demonstrated a significant difference in comparing with the control group, P < 0.01. The estradiol and prolactin levels of patients lowered significantly after JRL treatment, P < 0.05, while progestogen and testosterone increased significantly, P < 0.05, but no significantly change of follicle-stimulating hormone and luteinizing hormone was found. JRL showed marked effect in treating and preventing experimental HMG in rats, it could modulate the secretive function of sex hormone, and improve the construction of mammary gland., Conclusion: JRL has significant effect in treating HMG, it can adjust the endogenous sex hormone level, delay the development of chronic cystic hyperplasia of mammary gland.

Using a highly sensitive chemiluminescent enzyme immunoassay, we have evaluated the measurement of serum prostate-specific antigen (PSA) as a potential diagnostic test for differentiation between women with breast cancer and those with benign breast disease. In a controlled study consisting of 284 women with well-documented patient files and matched for age and long-term place of residence, serum samples collected from 90 women with histologically confirmed breast cancer, 94 women with benign breast disease and 100 controls were analysed. Serum total PSA levels in benign breast disease and cancer patients are not statistically different from those of healthy controls. Total PSA levels decrease with age in normal controls and breast cancer patients but not in those with benign breast disease. The total PSA concentration decreases after menopause in healthy women, though not in patients with breast cancer or benign breast disease. Total PSA bore no relation to the histological type or grade of the tumour or the disease stage of the breast cancer patients. In benign breast disease, all mastopathy patients had normal total PSA, whereas elevation of the values was observed in 7% of fibroadenoma patients. Our results show that serum total PSA cannot be used to distinguish between healthy women and/or women with breast cancer or benign breast disease.

We have analyzed matched serum and breast cyst fluid samples for total PSA from 148 patients with fibrocystic breast disease. We have also determined the molecular forms of PSA (free PSA and PSA bound to alpha1-antichymotrypsin) in 78 breast cyst fluid samples. We found that total PSA can be detected in all cyst fluids and in about 75% of female sera. The median total PSA concentration in breast cyst fluid (bcf) is about 30 times higher than the median in the corresponding sera. Breast cyst fluid and serum PSA are not correlated with each other. Total serum PSA is inversely associated with patient age but the inverse association between bcf PSA and age is weak. Lower total PSA in bcf was seen in women who breast feed, and higher bcf PSA is associated with multiple cysts. Type I cysts (with a high K+/ Na+ ratio) tend to have higher total PSA than Type II cysts. All but three of the fractionated cyst fluids (75/78; 96%) had free PSA as the predominant molecular form. The most consistent finding of our study was the positive association between the cyst fluid K+/Na+ ratio and the free to bound PSA ratio. This association was confirmed by Spearman correlation as well as by Wilcoxon and chi-square analysis. Secretory/apocrine cysts (Type I) tend to have more total PSA and proportionally more free PSA than transudative/flattened cysts (Type II).

The organochlorines, dichloro-diphenyl-trichloroethane and polychlorinated biphenyl (PCB) are pervasive environmental contaminants. Results from previous studies have been conflicting regarding the relationship between the internal dose of these organochlorine residues and breast cancer risk. To determine whether these compounds are present in breast cyst fluids and whether cyst fluid and plasma concentrations are correlated, we analyzed organochlorines in paired cyst fluid and plasma samples from 24 subjects using gas chromatography and electron capture detection. All but one of the women had a history of multiple cysts, suggesting that they were at elevated risk for future breast cancer. DDE (a metabolite of dichloro-diphenyl-trichloroethane) was present in 22 of the cyst samples and PCB was detected in 19 of the cyst samples. Organochlorine levels were more concentrated in the plasma than in breast cyst fluids. Levels of DDE in plasma were significantly correlated with those in cyst fluid (r = 0.73; P < 0.001); in contrast to PCB levels in cyst and plasma (r = 0.37; P = 0.12). Congener specific analysis of the PCBs showed that some individual congeners were preferentially excluded from or concentrated in the cyst fluid. To our knowledge, this study is the first to demonstrate that PCB and DDE are present in cyst fluids and thus in contact with the ductal epithelium of the breast. These results support the use of plasma DDE as a proxy for DDE in the target tissue in research on the role of environmental factors in breast cancer.

The study was carried out on 25 women with breast cancer, 25 with fibrocystic breast disease and 19 healthy subjects. Antioxidant enzyme activities and total antioxidant status (AOX) were measured in erythrocyte and plasma of patients and healthies. Among the studied parameters, the erythrocyte Glutathione Peroxidase (GSH-Px) and Catalase (CAT) activities of patients with breast cancer were significantly different as compared to the control group values (p < 0.002 and p < 0.001) respectively. There was no correlation between total antioxidant status and any of these enzymes in erythrocyte and plasma activities of subjects. However, the positive correlation was found between erythrocyte and plasma Superoxide Dismutase [SOD(CuZn)] activities in all groups. Our results indicate that enzymatic and nonenzymatic antioxidants are differentially altered in human breast tumors. Since the total antioxidant status measurement isn't sufficient to evaluate the oxidant damage in breast disease, antioxidant enzymes must be measured separately in order to get additional information.

There have been assessed selected hormonal parameters in patients with mastopathy in postmenopausal period. The hormonal evaluation showed significantly higher mean concentration of prolactin in blood serum of patients with mastopathy than in the blood serum of healthy women. There was not functional hyperprolactinaemia in the patients in postmenopausal period. In the examined patients in postmenopausal age, there was revealed significantly higher mean concentration of oestradiol in blood serum, in comparison with the healthy women. There was also found significantly lower mean concentration of follicle-stimulating and luteotrophic hormones, which is probably due to enhanced inhibition of gonadotrophic hormones secretion by prolactin and oestradiol. The results of the conducted hormonal examinations suggest that prolactin is an agent, which produces mastopatial changes in women. Furthermore, it seems that genesis of mastopathy in postmenopausal period may be connected not only with disprolactinaemia but also with persistent oestrogenic activity. It should be thus admitted that hormonal examinations (with particular consideration given to prolactin) are appropriate management in diagnosis and treatment of patients with mastopathy.

We have examined the predictive value of measurements of CASA (Cancer Associated Serum Antigen) levels in patients with breast carcinoma. The measurement uses monoclonal antibodies that bind to an epitope on the polymorphic epithelial mucin. CASA levels were of less value compared with the levels of other tumor markers (CA 15-3, CA 549 and CEA) in the management of patients with early breast cancer.

The usefulness of serum measurements of mucin-like carcinoma associated antigen (MCA) in 100 women at presentation with breast cancer was evaluated. Peripheral venous blood was drawn and MCA values determined by radioimmunoassay. Twenty women presenting with benign breast disease and 20 normal women served as controls. There was no difference in the MCA values between the benign breast disease group and the normal group: 4.1 +/- 0.9 units/ml versus 5.0 +/- 0.75 units/ml (mean +/- sem). The following were the MCA values for patients by stage; stage 1: 11.2 +/- 1.02, stage 2: 11.0 +/- 1.29, stage 3: 20.2 +/- 6.7, stage 4: 31 +/- 5.0. Statistical analysis of stage versus controls showed significant elevations only in stage 3 and 4 disease (p < 0.05). We conclude that MCA may be a useful serum tumour marker only in advanced breast cancer but is unreliable in detection of early breast cancer.

The activity of thymidine kinase, thymidine phosphorylase, adenosine deaminase and 5'-nucleotedase of AMP was studied in tissues, blood serum and lymphocytes of 60 healthy females and 50 females with fibrocavernous mastopathy aged 23-70. It was revealed that age-related changes in the activity of thymidine kinase in blood serum reflect the analogous changes in enzyme activity in tissues of healthy women. A direct correlation was established between thymidine kinase activity and age both in healthy females and those with mastopathy. A significant decrease in activity of thymidine phosphorylase was demonstrated in blood serum of patients with mastopathy aged 46-60. Determined 4-fold increase in activity of adenosine deaminase in serum was accompanied by decreased enzyme activity in lymphocytes and decreased Lymphocyte Blast Transformation Index in the same age range. The revealed metabolic changes in DNA-precursors' metabolism in patients with mastopathy aged 46-60 might be one of the reasons of increased risk of oncological diseases in this age group.

The adhesion of circulating cancer cells to the vascular endothelium is an important at step in the hematogenous metastasis of cancer. E-selectin expressed on endothelial cells and carbohydrate ligands expressed on cancer cells mediate this adhesion. We investigated the clinical significance of such cell adhesion molecules in breast cancer. The cytosol concentration of sialyl Lewis(x) was found more elevated in cancerous tissue than that in adjacent non-cancerous tissue. In the serum, sialyl Lewis(x) and soluble E-selectin were seen elevated in patients with advanced and recurrent breast cancer, especially in those with distant metastases. From the above, we have concluded that sialyl Lewis(x) and soluble E-selectin could be used as tumor markers with a close relationship to the metastasis of breast cancer.

Measuring the level of progesterone in 80 women who according to the ultrasound images had fibrocystic mastopathy. I've concluded by comparing the ultrasound images with the measurement of hormones that there was conformity of 75%.

Objectives: To develop an immunoassay for osteopontin (OPN), a secreted phosphoglycoprotein that is implicated in a number of human diseases, and establish basal plasma OPN levels in healthy women., Design and Methods: An antigen-capture ELISA was developed to quantity OPN in plasma using a combination of mouse monoclonal and rabbit polyclonal antibodies. Basal OPN levels were determined in blood plasma of 21 pre- and 14 postmenopausal women obtained at 7-day intervals over a 4-week period., Results: A group of 35 healthy women had a median OPN level of 31 micrograms/L (range = 14-64 micrograms/L). Comparison between pre- and postmenopausal women showed that their 4-week average OPN levels did not differ significantly (p > 0.16, Mann-Whitney test), and that levels in each premenopausal individual remained constant during the menstrual cycle, unaffected by cyclical levels of leuteinizing hormone and progesterone., Conclusion: Systematic quantification of plasma OPN can now be done by ELISA, which was used to establish basal plasma OPN levels in a group of healthy women. Levels in pre- and postmenopausal women appeared relatively stable over a 4-week period.

Benign mammary gross cystic disease is the most common breast lesion; women with apocrine changes of epithelium lining the cysts are at higher risk for developing breast cancer than the normal population. Total cholesterol, high- and low-density lipoproteins fractions, triglycerides and phospholipids, lipase activity and total lipid concentrations were measured in cyst fluids and sera from 89 women affected by gross cystic breast disease. Total cholesterol and high-density lipoprotein content were significantly (P < 0.001) greater in pooled cyst fluids than normal sera. Moreover, data analyses show a significant increase in the mean values of total lipids and lipase activity in metabolically active apocrine cysts, when compared to the flattened cysts (P < 0.001). The lipids feature of apocrine cysts could represent an altered expression of biosynthetic activity of the surrounding apocrine cell surface glycolipid and steroidogenic metabolism and may provide further knowledge about the functional stage changes of gross breast cysts.

Mammary serum antigen (MSA) serum levels were evaluated for its association with histopathologic outcome of breast biopsies. 212 women were undergoing a diagnostic extirpation for suspicious lesions of the breast. Invasive breast cancer was found in 24.5%, in-situ-carcinomas in 7.1% respectively. 56.1% of the women were diagnosed with proliferating benign breast diseases and normal breast tissue was found in 12.3% of the patients. In all women pretherapeutic MSA-serum levels were measured by Inhibition-ELISA using the monoclonal antibody 3E1.2. The positivity-rates of MSA, CA15-3, TPA and CEA were compared separately and in combination. MSA was positive in 25% of breast cancer patients when a cut-off level of 55 U/ml was applied. The addition of CA15-3, TPA or CEA increased the sensitivity to 42.3% and the increment of the positivity-rate was smaller by addition of CA15-3, when compared with TPA or CEA. The highest MSA serum levels and positivity-rates were associated with malignant tumours, but there was no significant difference compared with benign epithelial proliferations (19.5% positivity rate). The lowest positivity-rate was detected in mesenchymal proliferations of the breast (4.8%, p = 0.02). To sum up one can say that MSA serum levels do not allow to discriminate benign from malignant breast diseases and MSA is 2.5 to 3 times more sensitive for the prediction of early stages breast cancer compared to CA15-3, TPA and CEA.