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.

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.

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.

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.

Levels of serum 25-hydroxy-vitamin d in benign and malignant breast masses.

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.

[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.

Complement C3f serum levels may predict breast cancer risk in women with gross cystic disease of the breast.

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.

Usefulness of serum CA-15.3 in the management of benign breast lesion.

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.

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.

Hepatocyte growth factor in Egyptian females with breast benign lumps and cancers.

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.

[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--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 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.

Erythrocyte fatty acids and risk of proliferative and nonproliferative fibrocystic disease in women in Shanghai, China.

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.

[Metabolic syndrome and breast cancer risk in post-menopausal women]. / Sindromul metabolic si cancerul mamar la vârsta menopauzei.

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.

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.

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.