THE ROLE OF E2/P RATIO IN THE ETIOLOGY OF FIBROCYSTIC BREAST DISEASE, MASTALGIA AND MASTODYNIA.

- 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.

Leptin induces a proliferative response in breast cancer cells but not in normal breast cells.

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.

[Clinical comparision of alpha dihydroergocryptine against cabergoline in the treatment of the fibrocystic mastopathy]. / Comparación clínica de alfa dihidroergocriptina contra cabergolina en el tratamiento de la mastopatía fibroquística.

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.

Retinoids, carotenoids, and tocopherols in breast adipose tissue and serum of benign breast disease and breast cancer patients.

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.

Is hyperandrogenemia protective for fibrocystic breast disease in PCOS?

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.

[Variability in the frequency of TCR-mutant lymphocytes associated with gene polymorphisms in women living in radiation-polluted areas].

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.

[Prostate specific antigen--PSA and histopathological findings of endometrium in women with fibrocystic breast disease]. / Antygen specyficzny dla prostaty--PSA a obraz blony sluzowej macicy u kobiet ze zmianami mastopatycznymi gruczolów sutkowych.

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.

[Prostate specific antigen in women]. / Antygen specyficzny dla prostaty--PSA u kobiet.

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.

Prostate specific antigen in women with menstrual disturbances and fibrocystic mastopathy.

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.

Prostate-specific antigen in the serum of women with benign breast disease.

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.

Patients With Invasive Ductal Carcinoma Have Reduced Levels of Decorin Expression in Their Breast Tissue Compared to Patients With Fibroadenoma While Plasma Decorin Remains Unchanged.

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.

Plasma isoflavones and fibrocystic breast conditions and breast cancer among women in Shanghai, China.

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.

Effect of a low-fat diet on hormone levels in women with cystic breast disease. II. Serum radioimmunoassayable prolactin and growth hormone and bioactive lactogenic hormones.

For investigation of the bioactivity of circulating prolactin and growth hormone (lactogenic hormones) in symptomatic benign breast disease, serum was assayed by the Nb2 lymphoma cell method in premenopausal patients with cystic breast disease and cyclic mastalgia and in normal premenopausal women. The results were compared with serum prolactin and growth hormone concentrations determined by radioimmunoassay. The serum bioassayable hormone levels in the benign breast disease patients (74.0 +/- 77.6 ng/ml) were significantly higher (P less than .001) than in normal women (23.8 +/- 10.7 ng/ml). There were no significant differences in the radioimmunoassayable prolactin or growth hormone levels between the 2 groups. When 16 cystic breast disease patients were placed on a low-fat (20% of total kilocalories) diet for 3 months, there were significant reductions in the serum bioassayable hormone levels (P less than .02). It is concluded that the bioactivity of prolactin may be elevated in the serum of patients with cystic breast disease and cyclic mastalgia, without corresponding increases in levels determined by radioimmunoassay; that this abnormality is reversible by a reduction in dietary fat consumption to 20% of the total kilocalories; and that serum prolactin may provide a valuable biomarker in clinical trials of a low-fat diet in women at high breast cancer risk.

Effect of a low-fat diet on hormone levels in women with cystic breast disease. I. Serum steroids and gonadotropins.

For examination of the effect of a low-fat diet on serum estrogen, progesterone, and gonadotropin levels, 16 patients with cystic breast disease and cyclic mastalgia were studied before dietary intervention and at 2 and 3 months thereafter. Four-day food diaries indicated that total fat intake was reduced from a prediet average of 69 g (35% of total kilocalories/day) to an average of 32 g (21% of total kilocalories) after 3 months. Highly significant reductions (P less than .001) occurred in dietary cholesterol and less changes occurred in protein and total kilocalorie consumption (P less than .05); fiber intakes were not affected. After 3 months on this low-fat diet, there were significant reductions in luteal-phase serum total estrogens (P less than .001), estrone (P less than .005), and estradiol (P less than .01); progesterone, luteinizing hormone, and follicle-stimulating hormone levels were unchanged. Two of the 16 patients were excluded from the hormone statistical analyses because the serum progesterone levels were not consistent with sampling in the luteal phase of the menstrual cycle. It is concluded that a reduction of dietary fat intake to 20% of the total kilocalories will result in significant decreases in circulating estrogens in benign breast disease patients and that this effect is achievable without increasing dietary fiber consumption. Absence of changes in serum progesterone and gonadotropins during the dietary intervention is consistent with altered enterohepatic circulation of estrogens rather than with effects on the pituitary-ovarian axis.

Plasma equol concentration is not associated with breast cancer and fibrocystic breast conditions among women in Shanghai, China.

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.

Serum total and free prostate-specific antigen for breast cancer diagnosis in women.

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.

Organochlorine compounds (DDE and PCB) in plasma and breast cyst fluid of women with benign breast disease.

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.

Serum enterolactone levels and the risk of breast cancer in women with palpable cysts.

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.

Alpha 1-antichymotrypsin complexes in human breast cyst fluids.

Alpha 1-antichymotrypsin, a serum protease inhibitor, was found in 72 breast cyst fluids aspirated from women affected by gross cystic breast disease. When fractionated by gel chromatography, the presence of protein complexes or aggregates was demonstrated. A different distribution of the alpha 1-antichymotrypsin appeared to be related to the ionic composition of the breast cyst fluid; when compared with metabolically active apocrine cysts, a statistically significant increase of alpha 1 protease inhibitor values in flattened epithelial cysts was revealed (P < 0.001). Two-dimensional immunoelectrophoresis showed in apocrine cysts (Na/K ratio < 3) a characteristic double peak of alpha 1-antichymotrypsin immunoprecipitin curve. The relationship between this alpha 1 protease inhibitor and electrolyte profiles may provide further knowledge about the imbalance between proteases and their inhibitors on functional changes of gross cysts and might be useful in studies on their mechanism of formation and relationship to subsequent breast cancer.