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Background: The infertile women have an increased risk of developing benign and malignant tumors, in particular, breast cancer. Most studies have examined the role of gene variants in the risk of developing breast cancer, but there is little evidence of genetic risk factors for benign tumors., Aim: To assess the combined genetic risk of developing mastopathy in women with FSHR (rs6165, rs6166) and ESR1 (rs9340799, rs2234693) gene variants., Materials and Methods: The study included 87 infertile women (45 with concomitant fibrocystic mastopathy and 42 without mastopathy)., Results: For rs9340799 and rs2234693 variants of the ESR1 gene, we did not find any significant differences in the distribution of genotypes in infertile women with or without mastopathy. In patients with mastopathy, there was a reliable increase in the frequency of 307Ala/Ala and 680Ser/Ser genotypes of FSHR gene (χ 2  = 6.39, p = 0.012, OR = 4.49 (1.48-13.65)) as compared to patients without mastopathy. In the presence of 307Thr/Thr and 680Asn/Asn genotypes of the FSHR gene, a 4.88-fold reduction of mastopathy risk (χ 2  = 8.06, p = 0.005, OR = 0.21(0.07-0.59)) was observed. The frequency of the FSHR and the ESR1 genotypes combinations - 307Thr/Thr+680Asn/Asn+351AG+397TC was significantly decreased in patients with mastopathy., Conclusions: Our study did not find an association of ESR1 gene variants with the risk of developing of mastopathy in infertile women although heterozygous variants of the ESR1 gene enhanced the "protective" effect of FSHR gene variants and reduced the risk of mastopathy.

The risk of secondary tumors in patients who have received mediastinal radiation therapy is well-known. Microglandular adenosis of the breast is a rare lesion that is considered benign, although its possible role as a precursor of invasive breast carcinoma has been considered. We present a case of microglandular adenosis in a patient who received mediastinal radiation therapy in childhood for Hodgkin's lymphoma. To our knowledge, this is the first reported case of microglandular adenosis in a patient with mediastinal radiotherapy which may shed light on its pathogenesis., (Copyright © 2020 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.)

Diabetic mastopathy (DM) is a rare benign inflammatory disease of the breast, which nevertheless gives suspicious image of malignancy by breast ultrasound and mammography. MRI studies of this disease have indicated both nonspecific enhancement and non-enhancement of the lesion, depending on its degree of lymphocytic infiltration. This is the first case report discussing the appearances of DM on CESM, a novel mammographic technique., (© 2016 The Royal Australian and New Zealand College of Radiologists.)

Background: Monocentric cohorts suggested that radiation-induced CD8 T-lymphocyte apoptosis (RILA) can predict late toxicity after curative intent radiotherapy (RT). We assessed the role of RILA as a predictor of breast fibrosis (bf +) after adjuvant breast RT in a prospective multicenter trial., Methods: A total of 502 breast-cancer patients (pts) treated by conservative surgery and adjuvant RT were recruited at ten centers. RILA was assessed before RT by flow cytometry. Impact of RILA on bf + (primary endpoint) or relapse was assessed using a competing risk method. Receiver-operator characteristic (ROC) curve analyses were also performed in intention to treat. This study is registered with ClinicalTrials.gov, number NCT00893035 and final analyses are presented here., Findings: Four hundred and fifty-six pts (90.8%) were included in the final analysis. One hundred and eight pts (23.7%) received whole breast and node irradiation. A boost dose of 10-16 Gy was delivered in 449 pts (98.5%). Adjuvant hormonotherapy was administered to 349 pts (76.5%). With a median follow-up of 38.6 months, grade ≥ 2 bf + was observed in 64 pts (14%). A decreased incidence of grade ≥ 2 bf + was observed for increasing values of RILA (p = 0.012). No grade 3 bf + was observed for patients with RILA ≥ 12%. The area under the ROC curve was 0.62. For cut-off values of RILA ≥ 20% and < 12%, sensitivity and specificity were 80% and 34%, 56% and 67%, respectively. Negative predictive value for grade ≥ 2 bf + was equal to 91% for RILA ≥ 20% and positive predictive value was equal to 22% for RILA < 12% where the overall prevalence of grade ≥ 2 bf + was estimated at 14%. A significant decrease in the risk of grade ≥ 2 bf + was found if patients had no adjuvant hormonotherapy (sHR = 0.31, p = 0.007) and presented a RILA ≥ 12% (sHR = 0.45, p = 0.002)., Interpretation: RILA significantly predicts the risk of breast fibrosis. This study validates the use of RILA as a rapid screening test before RT delivery and will change definitely our daily clinical practice in radiation oncology., Funding: The French National Cancer Institute (INCa) through the "Program Hospitalier de Recherche Clinique (PHRC)".

Background and Purpose: The aim of this study is to assess the toxicity and cosmetic outcome of preoperative accelerated partial breast irradiation (PAPBI) for breast cancer patients with low risk on local recurrence., Material and Methods: Women aged ⩾60years with an invasive, unifocal ⩽3cm on MRI, (non-lobular) adenocarcinoma of the breast and a negative sentinel node received PAPBI (40Gray in 10 fractions over 2 weeks). Six weeks after radiotherapy a wide local excision was performed., Results: 70 patients with a median follow-up of 23 months (3-44 months) were evaluated. The overall postoperative infection rate was 11%. At 1, 2 and 3 years of follow-up respectively 89%, 98% and 100% of patients had no or mild induration-fibrosis. Fibrosis was only found in a small volume of the breast. The global cosmetic outcome was good to excellent in 77% at 6 months to 100% at 3 years. Two patients developed a local recurrence., Conclusion: Our first results show limited fibrosis in a small volume and good to excellent cosmetic outcome. In selected patients, preoperative radiotherapy appears to be a good option for breast conserving therapy., (Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Diabetic mastopathy is an uncommon, benign breast condition seen in type 1 and less frequently type 2 diabetic patients. It is characterized by a dense fibrous stromal proliferation of breast tissue, clinically mimicking cancerous masses, thus leading to worrisome investigations. Clinicians and pathologists must distinguish this benign condition from malignant causes because surgery may worsen the case as these lesions tend to recur more extensively at the site of resection. We present the case of a young woman with type 1 diabetes with typical diabetic mastopathy and summarize the literature to increase awareness of this troublesome but benign disorder., (Copyright © 2014 Canadian Diabetes Association. Published by 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: Adult alcohol consumption during the previous year is related to breast cancer risk. Breast tissue is particularly susceptible to carcinogens between menarche and first full-term pregnancy. No study has characterized the contribution of alcohol consumption during this interval to risks of proliferative benign breast disease (BBD) and breast cancer., Methods: We used data from 91,005 parous women in the Nurses' Health Study II who had no cancer history, completed questions on early alcohol consumption in 1989, and were followed through June 30, 2009, to analyze breast cancer risk. A subset of 60,093 women who had no history of BBD or cancer in 1991 and were followed through June 30, 2001, were included in the analysis of proliferative BBD. Relative risks (RRs) were estimated using Cox proportional hazard regression., Results: We identified 1609 breast cancer cases and 970 proliferative BBD cases confirmed by central histology review. Alcohol consumption between menarche and first pregnancy, adjusted for drinking after first pregnancy, was associated with risks of breast cancer (RR = 1.11 per 10 g/day intake; 95% confidence interval [CI] = 1.00 to 1.23) and proliferative BBD (RR = 1.16 per 10 g/day intake; 95% CI = 1.02 to 1.32). Drinking after first pregnancy had a similar risk for breast cancer (RR = 1.09 per 10 g/day intake; 95% CI = 0.96 to 1.23) but not for BBD. The association between drinking before first pregnancy and breast neoplasia appeared to be stronger with longer menarche to first pregnancy intervals., Conclusions: Alcohol consumption before first pregnancy was consistently associated with increased risks of proliferative BBD and breast cancer.

Previous investigations found high dairy intakes in girls associated with rapid height growth and excess weight gain, which had opposite relationships with benign breast disease (BBD) in young women. We use data from the longitudinal Growing Up Today Study (GUTS) to investigate whether dairy intakes, in older children/adolescents, are associated with BBD risk in young women. GUTS includes 9,039 females, ages 9-15 years in 1996, who completed questionnaires annually through 2001, then in 2003, 2005, 2007, and 2010. Dietary food frequencies (1996-2001) obtained milk, yogurt, and cheese intakes. On 2005-2010 surveys, 7,011 females (18-29 years) reported whether a health care provider ever diagnosed them with BBD (n = 250) and if confirmed by breast biopsy (n = 105). Logistic regression models estimated associations between prevalent biopsy-confirmed BBD and dairy intakes, adjusted for age and energy. Multivariable-adjusted models additionally included menarche age, childhood adiposity, adolescent alcohol consumption, and pregnancy. Further analyses stratified by family history. Age-energy-adjusted models of dairy (milk, yogurt, cheese, total dairy servings, dairy protein, dairy fat) intakes at 14 yr found no significant associations with BBD risk [milk: OR, 0.90/(serving/d); 95% confidence interval (CI), 0.76-1.05; dairy protein: OR, 0.98/(10 g/d); 95% CI, 0.82-1.17). Separate analyses of dairy intakes at 10 yr, intakes before the growth spurt, during the growth spurt, before menses-onset, and after menses-onset provided no significant associations with BBD. Multivariable adjustment, and family history stratification, did not alter the above findings. We conclude that dairy intakes by older girls have no strong relation with BBD risk in young women. Because of small number of cases, it is important to continue follow-up and re-examine later.

The appearance of endometrial cancer in adolescence is uncommon and warrants investigation for an hereditary cancer syndrome. Cowden syndrome is an autosomal dominant cancer syndrome associated with a germline PTEN mutation and increased risk of breast, thyroid, endometrial and colon cancer. In this report we present a case of a 14-year-old nulligravid female diagnosed with grade 1 endometrial adenocarcinoma. She subsequently developed fibrocystic breast disease and colon polyps and was diagnosed with Cowden syndrome at age 20. We therefore recommend formal evaluation for Cowden syndrome to be considered when endometrial cancer is diagnosed in adolescence., (© 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.)

Background: Diabetic mastopathy is a rare condition, which is clinically not easily to differentiate from breast cancer., Case Description: A 32-year-old woman, with a long-standing history of insulin-dependent diabetes mellitus presented at the breast outpatient clinic with a firm palpable, painless mass in her right breast. Mammography and ultrasound examination showed, respectively, slight asymmetry with dense glandular tissue and a hypoechoic area with posterior shadowing. MR mammography showed no suspicious abnormalities. Histopathological examination revealed fibrous tissue with lymphocytic inflammation. The combination of clinical presentation, history of diabetes mellitus, and histological findings led to a diagnosis of diabetic mastopathy., Conclusion: A palpable breast abnormality in a woman with diabetes mellitus can be caused by diabetic mastopathy. Knowledge of this condition by the disciplines involved can prevent over-diagnosis and unnecessary interventions.

A 64-year-old postmenopausal female had been treated with insulin therapy for type 2 diabetes mellitus for 18 years, but her diabetes mellitus was not well controlled and she developed retinopathy. Her screening mammography showed abnormal findings, and thus she consulted a hospital. A physical examination showed her mammary glands to be hard on both sides and no palpable mass was observed. Mammography revealed an amorphous calcification in the middle outer portion of the left breast. Ultrasonography showed an irregular hypoechoic mass measuring about 11 mm in size in the upper outer portion of the left breast. Although a core-needle biopsy specimen of the hypoechoic mass showed hyalinizing fibrosis without any evidence of malignancy, a stereotactic guided vacuum-assisted biopsy was performed because magnetic resonance imaging revealed an enhanced area in the region of the amorphous calcification that could not be distinguished from breast cancer. The histological findings indicated noninvasive ductal carcinoma, and therefore a quardrantectomy with a sentinel lymph node biopsy was performed. The pathological diagnosis was invasive ductal carcinoma (0.7 × 0.3 cm) with a predominant intraductal component accompanying diabetic mastopathy. The sentinel lymph nodes demonstrated no metastasis. The surgical margin was positive for carcinoma and the patient later underwent a mastectomy. No malignant cells were observed in the specimen. The patient has so far experienced no recurrence after surgery.

Extranodal NK/T-cell lymphoma, nasal type, is a rare type of non-Hodgkin lymphoma that is most common in Asia and is driven by Epstein-Barr virus infection. These tumors usually arise in the nasal region; in rare cases they can involve extranasal sites, most often skin, with involvement of the breast being rare. Lymphomas arising adjacent to breast implants are rare, and most cases reported to date have been anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma. Here we report a 41-year-old white woman with bilateral saline breast implants placed for cosmetic reasons who almost 9 years later developed painful swelling at the right-breast implant site. Excisional biopsy revealed lymphoma composed of monomorphic large cells associated with necrosis and angioinvasion. Immunohistochemical analysis showed an aberrant, NK/T-cell immunophenotype with the lymphoma cells being CD2+, CD3+, CD56+, partial CD30+, granzyme B, TIA-1+, CD4+, CD5+, CD7+, and CD8+. In situ hybridization analysis showed Epstein-Barr virus-encoded RNA within the neoplastic cells. Polymerase chain reaction analysis showed monoclonal T-cell receptor-γ chain gene rearrangement. These findings support the diagnosis of extranodal NK/T-cell lymphoma, nasal type. On the basis of our review of the literature, this case is unique. In addition, we believe this case is important to report, because it expands the spectrum of T-cell lymphomas that can be associated with breast implants and may be a forerunner of additional cases to follow.

Diabetic mastopathy (DMP) is an uncommon collection of clinical, radiological, and histological features, classically described in premenopausal women with long-term insulin-dependent diabetes mellitus. This entity can mimic breast carcinoma, but, in the appropriate clinical and imaging setting, the diagnosis can be made by core biopsy, avoiding unnecessary surgeries. We report the case of a 34-year-old female, with a 12-year history of type 1 diabetes, who presented with bilateral breast lumps. Mammography, ultrasonography, and magnetic resonance imaging could not exclude the suspicion of malignancy, and a core biopsy was performed showing the typical histologic features of DMP. The literature is briefly reviewed., (Copyright © 2012 Elsevier Inc. 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.

Objectives: To examine the combined effect of alcohol and folate intake during adolescence on the risk of proliferative benign breast disease (BBD)., Methods: We used data from 29 117 women in the Nurses' Health Study II who completed both adolescent alcohol consumption questions in 1989 and an adolescent diet questionnaire in 1998. A total of 659 women with proliferative BBD diagnosed between 1991 and 2001 were confirmed by central pathology review. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals (CIs), adjusted for established risk factors of breast cancer., Results: Adolescent alcohol consumption was dose-dependently associated with an increased risk of proliferative BBD (hazard ratio = 1.15 per 10 g/day consumption; 95% CI, 1.03-1.28). There was no significant association between adolescent folate intake and the risk of proliferative BBD. Stratified analyses showed that each 10-g/day alcohol intake during adolescence was associated with a 21% (95% CI, 1.01-1.45) increase in the risk of proliferative BBD among women with low folate intake during adolescence, which was not significantly different from the alcohol-associated risk among women with moderate and high folate intake during adolescence (P for interaction = 0.18)., Conclusions: Adolescent alcohol consumption is associated with increased risk of proliferative BBD, which may not be reduced by increased folate intake during adolescence.

Background: The American Society of Breast Surgeons (ASBrS) enrolled women in a registry trial to prospectively study patients treated with the MammoSite RTS device. This report presents 6-year data on treatment-related toxicities from the trial., Methods: A total of 1449 primary early-stage breast cancers were treated with accelerated partial breast irradiation (APBI) using the MammoSite device (34 Gy in 10 fractions) in 1440 women. Of these, 1255 case (87%) had invasive breast cancer (IBC) (median size = 10 mm) and 194 cases (13%) had ductal carcinoma in situ (DCIS) (median size = 8 mm). Median follow-up was 59 months. Fisher exact test was performed to correlate categorical covariates with toxicity., Results: Breast seromas were reported in 28% of cases (35.5% with open cavity and 21.7% with closed cavity placement). Also, 13% of all treated breasts developed symptomatic seromas, and 77% of these seromas developed during the 1st year after treatment. There were 172 cases (11.9%) that required drainage to correct. Use of chemotherapy and balloon fill >50 cc were associated with the development of symptomatic seromas. Also, 2.3% of patients developed fat necrosis (FN). The incidence of FN during years 1 and 2 were 0.9% and 0.8%, respectively. Seroma formation, use of hormonal therapy, breast infection, and A/B cup size were associated with fat necrosis. There were 138 infections (9.5%) recorded; 98% occurred during the 1st year after treatment. Chemotherapy and seroma formation were associated with the development of infections., Conclusions: Treatment-related toxicities 6 years after treatment with APBI using the MammoSite device are similar to those reported with other forms of APBI with similar follow-up.

The article presents results obtained in study of relationship between polymorph variants of CYP1A1 and CYP1A2 genes with reproductive and thyroid diseases risk in female workers of petrochemical industry, when compared with reference group females. Variants TD and DD of CYP1A2 gene appeared to be associated with nodes formation in uterus and breast in female workers and reference group females. Following liability markers are obtained: homozygous in rare allele genotype CC of CYP1A1 gene for reproductive and thyroid diseaes (fibrous cystic mastopathy and nodular goitre), heterozygous genotype AG of CYP1A1 gene in uterine myoma and fibrous cystic mastopathy, homozygous in deleted T genotype of CYP1A2 gene in autoimmune thyroiditis. Occupational hazards and long length of service at hazardous industries increase effects of rare alleles of the genes studied.

The present review outlines the various issues of breast pathology in diabetes. Diabetic mastopathy is an uncommon proliferation of fibrous tissue in the breast that mimics tumour. Breast arterial calcifications represent calcium deposits in the media of arterioles and are more frequently detected on mammograms of diabetic subjects. Importantly, type 2 diabetes mellitus (T2DM) has been associated with breast cancer, but the mechanism underlying this association is complex, since the two entities frequently co-exist and seem to share common aetiological factors and pathways. Furthermore, diabetes has been suggested to negatively affect breast cancer outcomes, but it is unclear whether better glycaemic control would ameliorate prognosis. Preliminary data suggest that antidiabetic treatment may also influence both the incidence and prognosis of breast cancer. However, available evidence is inconclusive and further research is needed. Therefore, treatment of diabetes should not be determined by its potential effect on breast cancer., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Diabetic mastopathy is an uncommon benign entity occurring in young women with type 1 diabetes. Its clinical and radiological signs are not specific and often mimic a breast carcinoma. However, the benign nature of this lesion is easily recognized on histological examination, visualizing dense keloid-like fibrosis, lymphocytic lobulitis and ductitis with lymphocytic perivascular inflammation, with or without epithelioid-like fibroblasts. Surgery can generally be avoided. The evolution of this entity is characterized by the risk of local growth, bilateralisation or recurrence after surgical treatment. We present a case in which the core biopsy allowed the diagnosis of a diabetic mastopathy and we discuss its clinical, diagnostic, pathological and therapeutic particularities., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Objective: To investigate prospectively, using alcoholic beverage consumption data collected in real time, the association between adolescent drinking and risk of biopsy-confirmed benign breast disease (BBD) in young women., Participants and Methods: The Growing Up Today Study is a prospective cohort study of US girls, aged 9 to 15 years at baseline, with annual questionnaires from 1996 through 2001, followed by questionnaires in 2003, 2005, and 2007. On the 2003 survey, the participants (then aged 16-23 years) provided information about their alcoholic beverage consumption in the previous year. On the 2005 and 2007 surveys, a total of 6899 women (aged 18-27 years) reported whether a health care provider had ever diagnosed them with BBD (n = 147 cases) and whether it was confirmed by biopsy (n = 67 cases); 6752 women reported never being diagnosed with BBD., Results: Adjusted for age and BMI, quantity of alcohol consumed was associated with increased risk of biopsy-confirmed BBD (odds ratio: 1.50 per drink per day [95% confidence interval: 1.19-1.90]). Girls who typically drank 6 or 7 days/week were at higher risk (odds ratio: 5.50 [95% confidence interval: 1.23-24.53]) compared with those who never drank or who drank less than once per week., Conclusions: Higher amounts consumed, and more frequent consumption, of alcoholic beverages in adolescence may increase the occurrence of BBD in young women. Advising teenagers to avoid alcoholic beverages, along with smoking and sun exposure, may reduce cancer incidence in adulthood.

Gross cystic breast disease (GCBD) is the most common benign breast disorder, but the molecular basis of cyst formation remains to be identified. If the use of aluminium-based antiperspirant salts is involved in the etiology of gross breast cyst formation, it might be expected that aluminium would be at elevated levels in human breast cyst fluid (BCF). Aluminium was measured by ICP-MS in 48 samples of BCF, 30 samples of human blood serum and 45 samples of human breast milk at different stages of lactation (colostrum, intermediate, mature). The median level of aluminium in apocrine type I BCF (n = 27, 150 microg l(-1)) was significantly higher than in transudative type II BCF (n = 21, 32 microg l(-1); P < 0.0001). By comparison, aluminium measurements gave a median concentration of 6 microg l(-1) in human serum and 25 microg l(-1) in human breast milk, with no difference between colostrum, intermediate and mature milk. Levels of aluminium were significantly higher in both types of BCF than in human serum (P < 0.0001). However when compared with human breast milk, aluminium levels were only significantly higher in apocrine type I BCF (P < 0.0001) and not in transudative type II BCF (P = 0.152). It remains to be identified why such high levels of aluminium were found in the apocrine type I BCF and from where the aluminium originated. However, if aluminium-based antiperspirants are found to be the source and to play any causal role in development of breast cysts, then it might become possible to prevent this common breast disorder., (Copyright (c) 2008 John Wiley & Sons, Ltd.)

We report a case of diabetic mastopathy in a man with type 2 diabetes. The patient was a 62-year-old man who had been diagnosed with type 2 diabetes at the age of 46 years. He had been treated with oral hypoglycemic agents. He noticed a mass in his left breast in February 2007, when HbA(1)c was 7.6% with the treatment using oral hypoglycemic agents, including acarbose, glimepiride, buformine, and pioglitazone. Mammography of the breast showed increased density, and ultrasonography showed a regular-shaped hypoechoic mass. Core needle biopsy was performed, and diabetic mastopathy was confirmed pathologically. Diabetic mastopathy usually occurs in women with type 1 diabetes. This case, a man with type 2 diabetes, is very rare.

Modifiable factors, including diet, might alter breast cancer risk. We used the Women's Health Initiative Dietary Modification trial to test the effect of the intervention on risk of benign proliferative breast disease, a condition associated with increased risk of, and considered to be on the pathway to, invasive breast cancer. The Women's Health Initiative Dietary Modification trial was a randomized, controlled, primary prevention trial conducted in 40 U.S. clinical centers from 1993 to 2005. A total of 48,835 postmenopausal women, ages 50 to 79 years, without prior breast cancer, were enrolled. Participants were randomly assigned to the dietary modification intervention group or to the comparison group. The intervention was designed to reduce total dietary fat intake to 20% of total energy intake, and to increase fruit and vegetable intake to > or =5 servings/d and intake of grain products to > or =6 servings/d, but resulted in smaller, albeit significant, changes in practice. Participants had biennial mammograms and regular clinical breast exams. We identified women who reported breast biopsies free of cancer, obtained the histologic sections, and subjected them to standardized central review. During follow-up (average, 7.7 years), 570 incident cases of benign proliferative breast disease were ascertained in the intervention group and 793 in the comparison group. The hazard ratio for the association between dietary modification and benign proliferative breast disease was 1.09 (95% confidence interval, 0.98-1.23). Risk varied by levels of baseline total vitamin D intake but it varied little by levels of other baseline variables. These results suggest that a modest reduction in fat intake and increase in fruit, vegetable, and grain intake do not alter the risk of benign proliferative breast disease.

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.

Sclerosing lymphocytic lobulitis is strongly associated with type one diabetes, when it is then known as diabetic mastopathy. This very rare benign condition tends to present in premenopausal women, often with diabetic complications particularly retinopathy. Patients present with clinically suspicious fibrous breast lumps; these are commonly multiple, bilateral, and recurrent. Mammograms show asymmetric densities and no focal mass and ultrasound investigation tends to show ill-defined hypoechoic attenuation with strong posterior acoustic shadowing. Magnetic resonance imaging can be used to further differentiate the lesion from malignancy. However, a core biopsy or excisional biopsy is essential so that a pathologic diagnosis can be made. The constellation of pathologic findings is: lymphocytic lobulitis and ductitis with glandular atrophy, lymphocytic/mononuclear perivascular inflammation which is predominantly B-cell and dense often keloid-like fibrosis, with or without epithelioid-like fibroblasts. A review of the current literature on diabetic mastopathy was carried out as it was noted that there has been no recent review of the literature. Detailed Pubmed and other medical data base searches were carried out and all publications were considered, irrespective of language and date, wherever possible.

Objective: To evaluate the biological behavior and treatment method for the breast atypical lobular hyperplasia (ALH) and breast lobular carcinoma in situ (LCIS)., Methods: Seventeen cases of ALH and thirty-five cases of LCIS were reviewed from July 1982 to January 1996. All cases were followed by physical examination, mammography and B-ultrasound for an average of 146.6 months (range, 3 - 257 months)., Results: Most cases of ALH and LCIS occurred before menopause (about 69.2%). Fifty-two cases of ALH and LCIS were occasionally verified pathologically after surgery for benign diseases. The microcalcification with ALH and LCIS had been detected in 25 cases, accounted for 48.1%. Eight cases of ALH/LCIS became invasive carcinoma. There were 5 cases in the same breast, 3 cases in the contralateral breast; The subsequent breast cancer occurred longer than nine years after ALH/LCIS was diagnosed. The family history of breast carcinoma and ovary carcinoma occurred in 4 cases of breast carcinoma, accounted for 50%, but it was no significant (P > 0.05). Also, there was no difference between LCIS and ALH, which occurred the breast carcinoma (P > 0.05)., Conclusion: The excisional biopsy might be necessary to ALH and LCIS.

Spontaneous mammary tumors were seen in seven of the 12 breeding female rats aged 2 years. All mammary tumors were diagnosed as mammary dysplasia (MD). Bone mineral contents (BMC) and bone mineral density (BMD) of their lumbar vertebrae and femur were determined using dual energy X-ray absorptiometry (DXA). In rats with MD, body weight (BW), BMD of the lumbar vertebrae and BMC of the femur were significantly higher than in the rats without MD. Although corpus luteum (CL) and follicles were seen in the ovaries of all animals, the number of CL in rats with MD was significantly lower than the rats without MD. It was suggested that high BMD, BW and decreased CL promoted mammary tumors.

Objective: To observe the changes of mental stress life events (MSLE) in patients with cyclomastopathy of liver stagnation syndrome type (LSS)., Methods: Clinical epidemiological research method was adopted, the changes of MSLE were observed in cyclomastopathy patients of LSS or non-LSS, classified by syndrome differentiation of TCM., Results: Not only the mean age (33.38 +/- 6.76 years) of patients with LSS was obviously lower than that of patients with non-LSS (38.36 +/- 9.89 years, P < 0.01), but also the mean age of patients with moderate and serious symptoms of LSS (33.96 +/- 7.31 and 37.43 +/- 7.38 years) were higher than that of patients with mild symptoms of LSS (31.67 +/- 5.39 years, P < 0.05 and P < 0.01). MSLE score of patients with LSS (32 scores) was significantly higher than that of patients with non-LSS (22 scores, P < 0.01). MSLE score of patients with moderate and serious LSS was 34.69 +/- 17.78 scores and 51.65 +/- 20.75 scores respectively, both were significantly higher than that of patients with mild LSS (26.57 +/- 15.85 scores, P < 0.05 and P < 0.01)., Conclusion: The high incidence age of cyclomastopathy is under 40 years, and most of cyclomastopathy patients are classsified to LSS by TCM syndrome differentiation. So age and life event scores may be the objective bases for syndrome typing and liver stagnation syndrome grading in patients with cyclomastopathy.

The hedgehog signaling network regulates pattern formation, proliferation, cell fate and stem/progenitor cell self-renewal in many organs. Altered hedgehog signaling is implicated in 20-25% of all cancers, including breast cancer. We demonstrated previously that heterozygous disruption of the gene encoding the patched-1 (PTCH1) hedgehog receptor, a negative regulator of smoothened (Smo) in the absence of ligand, led to mammary ductal dysplasia in virgin mice. We now show that expression of activated human SMO (SmoM2) under the mouse mammary tumor virus (MMTV) promoter in transgenic mice leads to increased proliferation, altered differentiation, and ductal dysplasias distinct from those caused by Ptch1 heterozygosity. SMO activation also increased the mammosphere-forming efficiency of primary mammary epithelial cells. However, limiting-dilution transplantation showed a decrease in the frequency of regenerative stem cells in MMTV-SmoM2 epithelium relative to wild type, suggesting enhanced mammosphere-forming efficiency was due to increased survival or activity of division-competent cell types under anchorage-independent growth conditions, rather than an increase in the proportion of regenerative stem cells per se. In human clinical samples, altered hedgehog signaling occurs early in breast cancer development, with PTCH1 expression reduced in approximately 50% of ductal carcinoma in situ (DCIS) and invasive breast cancers (IBC). Conversely, SMO is ectopically expressed in 70% of DCIS and 30% of IBC. Surprisingly, in both human tumors and MMTV-SmoM2 mice, SMO rarely colocalized with the Ki67 proliferation marker. Our data suggest that altered hedgehog signaling may contribute to breast cancer development by stimulating proliferation, and by increasing the pool of division-competent cells capable of anchorage-independent growth.

We report a case of diabetic mastopathy in an elderly woman with type 2 diabetes. The patient was a 69-year-old woman diagnosed with type 2 diabetes at the age of 33 years. She had been treated with insulin for 25 years, however, her blood glucose had been poorly controlled. She noticed bilateral breast lumps in September 2002. Mammography of the breast showed increased density in the glandular pattern and architectural distortion without focal mass and microcalcification. Ultrasonography of the breast showed an irregular-shaped hypoechoic mass with an acoustic shadow. As malignancy needed to be excluded, core needle biopsy was performed in the left breast and diabetic mastopathy was confirmed pathologically. Diabetic mastopathy is usually a complication of pre-menopausal type 1 diabetes and develops in a unilateral breast. This case developed in bilateral breasts in an elderly type 2 diabetic patient.

Objectives: To briefly review previously published evidence for Helicobacter pylori (Hp), colonization of extra-intestinal sites and suggest an hypothesis that breast acini and ducts be added to this list, concluding such breast colonization is not rare and is a sexually transmitted infection., Methods: PubMed literature search and review with a case report., Conclusions: (1) Evidence indicates oral Hp is common and can remain in the mouth after successful eradication in stomach and duodenum. (2) Evidence indicates that the breast is also occasionally colonized by Hp. (3) Hp may be injected retrograde up into ducts of the breast during oral nipple stimulation during sexual activity and this Hp may give rise to some cases of fibrocystic breast change. (4) A case of painful fibrocystic change that had been present for two years in a 27 year old female, resolved after gastrointestinal Hp treatment.

The reference data contain a lot of information on the interrelation between destroying of a thyroid gland and fibrocystic diseases. However contradictions in these data proves that this issue is not solved completely. The aim of the given study was the investigation of interrelations between frequency of occurrence of pathology of a functional condition of the thyroid gland and the frequency of occurrence of fibrocystic diseases. 90 women aged 23-50 were investigated. Concentration of thyroxin (FT4), thyrotrophic hormone (TSH), titers of antibodies to thyreoperoxidase, microsomal fraction of thyreocytes and thyreoglobulin were measured by ELISA. Palpation and ultrasonic investigations of thyroid and mammary glands were used, morphology of central formations of mammary glands according to indications was also carried out. A special questionnaire was completed for each patient. Our investigations showed that along with the declining of function of thyroid gland and the increased level of TSH in the blood, the risk of development of fibrocystic diseases is increased twice.

Objective and Importance: Lhermitte-Duclos disease, or dysplastic cerebellar gangliocytoma is a rare entity characterized by a hamartomatous lesion in the posterior fossa. Cowden's syndrome, or hamartoma-neoplasia syndrome is a rare underdiagnosed autosomal dominant genodermatosis with high incidence of malignant tumors. Several recent reports suggest that Lhermitte-Duclos disease may be a component of Cowden's syndrome., Clinical Presentation: We report two cases of Lhermitte-Duclos and Cowden disease occurring in adult patients. A 40-year-old woman had symptoms of raised intracranial pressure and macrocephaly. She displayed the stigmata of fibrocystic breast disease, thyroid goitre. Clinical examination showed mucocutaneous lesions. Her mother, brother and uncle had manifestations of Cowden's disease. An asymptomatic 38-year-old male had bilateral optic nerve drusen related to a cerebellar neoplasm. He exhibited manifestations of Cowden's syndrome and his familial history confirmed this hypothesis., Intervention: The first patient was operated on for Lhermitte-Duclos disease. A conservative strategy was performed for the second patient and the clinical and imaging follow-ups were uneventful over 5 years., Conclusion: We stress the possibility that Lhermitte-Duclos and Cowden disease might be a peculiar form of phakomatosis. A conservative strategy can be chosen without neurological signs because of slow tumor growth. However, these patients should be carefully examined and followed up because of the risk of future malignancy.

Objective: To compare therapeutic effects of red-hot needle therapy and filiform needle therapy on nodules of breast of the type of stagnation of liver-qi and phlegm coagulation., Methods: Six hundred cases were randomly divided into a treatment group and a control group, 300 cases in each group. The treatment group were treated with red-hot needle pricking at the proliferative parts and Ashi points as main, and the control group with filiform needle therapy., Results: In the treatment group, 240 cases were cured, 58 cases improved and 2 cases were not cured with an effective rate of 99.3%; and in the control group, 113 cases were cured, 165 cases improved and 22 were not cured with an effective rate of 92.7%, with a significant difference between the two groups (P = 0.001)., Conclusion: The therapeutic effect of red-hot needle therapy is better than that of filiform needle therapy on nodules of breast of the type of stagnation of liver-qi and phlegm coagulation.

We investigated whether circulating insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) levels are associated with the risk of fibrocystic breast conditions (FBC), in a case-control study nested within a randomized trial of breast self-examination conducted in Shanghai, China. Participants were enrolled during 1989-1991 and were followed over 10 years for the development of breast diseases. Controls (n = 897) were frequency-matched by age to cases (n = 451), who were diagnosed with FBC between 1995 and 2000. Circulating IGF-I and IGFBP-3 levels and their molar ratio were positively associated with risk of FBC. The odds ratios (ORs) and 95% confidence intervals (CI) for the upper fourth of the distribution compared to the lowest fourth for IGF-I, IGFBP3 and their molar ratio were 3.02 (2.02-4.52), 1.92 (1.37-2.71) and 2.26 (1.52-3.36), respectively. The strength of the association between IGF-I levels and FBC was attenuated after adjustment for IGFBP-3 and that for IGFBP-3 was largely eliminated after adjustment for IGF-I. Increasing levels of IGF-I were particularly associated with increasing risk of FBC with proliferative elements (ORs and 95% CIs for the 2nd, 3rd and upper fourth of the distribution of IGF-I: 3.13 (1.50-6.53), 4.57 (2.22-9.39) and 6.30 (3.08-12.89), compared with the lowest fourth. Our results suggest that elevated levels of IGF-I may contribute to the development of FBC., (2005 Wiley-Liss, Inc.)

Diabetic mastopathy is an uncommon tumor-like proliferation of fibrous tissue of the breast that usually occurs in a patient who has suffered from type I diabetes mellitus of long duration. Here we report a rare case of diabetic mastopathy that occurred in type II non-insulin dependent diabetes mellitus. This patient was a 63-year-old postmenopausal woman. Mammography, ultrasonography and MR imaging could not distinguish it from breast cancer. Although the core needle biopsy specimen showed fibrosis without evidence of malignancy, excisional biopsy was performed. Histological findings demonstrated typical diabetic mastopathy with keloid-like fibrosis, perivascular lymphocytic infiltration, and lymphocytic lobulitis without evidence of malignancy. These lymphocytes were composed predominantly of B-cells. Five months after surgical biopsy, a nodular formation approximately 4 cm in diameter recurred adjacent to the resected end of the biopsy.

Proliferative benign breast disease is a marker of increased breast cancer risk, yet little is known about its etiology. Most studies of benign breast disease have focused only on risk factors in adulthood, despite growing evidence that factors in early life influence breast cancer risk. We explored the relations of several early life factors with incidence of proliferative benign breast disease among 71,896 premenopausal women in the Nurses' Health Study II who recalled their body fatness at young ages, physical activity in adolescence, birthweight, and history of being breastfed. Between 1991 and 1997, 901 of these women were identified as having proliferative benign breast disease from a centralized pathology review. Relative risks (RR) and 95% confidence intervals (95% CI) were estimated from Cox proportional hazards models. Greater childhood body fatness (ages 5-10) was associated with decreased risk of proliferative benign breast disease; the multivariate RR (95% CI) for the most overweight compared with the most lean was 0.61 (0.44-0.86; P(trend) < 0.0001) and remained significant after adjustment for current body mass index. Body mass index at age 18 was also inversely associated with incidence of proliferative benign breast disease, with a multivariate RR (95% CI) of 0.67 (0.52-0.88) for those who were > or =25 kg/m(2) compared with those who were <19 kg/m(2) (P(trend) = 0.001). There were no clear associations for physical activity in adolescence, birthweight, or being breastfed. These results indicate that premenopausal women who were heavier at young ages have lower incidence of proliferative benign breast disease, consistent with previous findings for breast cancer.

Risk of breast cancer is increased in women with proliferative benign breast conditions. Most of these conditions, however, do not progress to breast cancer. The purpose of our study was to identify factors possibly associated with this progression. Women with proliferative fibrocystic breast conditions alone (214), and women with proliferative fibrocystic breast conditions and concurrent breast cancer (130), were compared to each other, and each of these groups of women were also compared to 1,070 controls; and 176 women with non-proliferative benign breast conditions alone, and 155 also with breast cancer, were similarly compared. All study subjects were selected from a cohort of women enrolled in a trial of breast self-examination in Shanghai. Women were interviewed to ascertain information on suspected risk factors for breast cancer and dietary habits. Conditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Increased risks of both proliferative fibrocystic breast conditions alone, and with breast cancer, were associated with low parity, a prior benign breast lump and breast cancer in a first-degree relative. Decreasing trends in the risk of both conditions with increasing intake of fruits and vegetables were observed. No factors were significantly associated with risk of breast cancer relative to risk of proliferative changes. Similar, but in some instances weaker, associations were observed for non-proliferative fibrocystic conditions with and without breast cancer. The possible risk or protective factors that were observed in our study most likely alter the risk of breast cancer at an early stage in the carcinogenic process, and probably do not alter risk of progression from proliferative fibrocystic breast conditions to breast cancer., (Copyright 2005 Wiley-Liss, Inc.)

Fibrous and inflammatory lesions of the breast in patients with early-onset, longstanding insulin-dependent diabetes mellitus (IDDM) can lead to misdiagnosis because the clinical, mammographic, and sonographic findings simulate breast cancer. We report a case of diabetic fibrous mastopathy with suspicious clinical, imaging, and cytologic findings., (2004 Wiley Periodicals, Inc.)

Diabetic mastopathy can mimic cancer. We report 2 cases of diabetic mastopathy in patients with long-standing type II diabetes. One was insulin-dependent, and the other had never been treated with insulin. These 2 patients had classical acoustical shadow on ultrasonograms. Breast core biopsies showed constellations of morphological features resembling diabetic mastopathy, including sclerotic changes of the fibrous stroma with keloid-like collagen fibers, few epithelioid fibroblasts, perivascular and interlobular mononuclear cell infiltrates, and focal atrophic changes of the ductal-lobular units. Both patients were free of malignancy at 3 and 4 years of follow-up, respectively. There are limited data on diabetic mastopathy in insulin-naive type II diabetes mellitus patients. Better awareness of this entity and its sonographic features may allow more patients to be spared from excisional biopsy.

This study was conducted to identify reproductive and dietary factors associated with benign proliferative mammary epithelial cell changes. Subjects were women enrolled in a randomized trial of breast self-examination in Shanghai, China. Women who developed fibrocystic breast conditions classified as nonproliferative (175 women), proliferative (181 women), or proliferative with atypia (33 women) between 1995 and 2000 and 1,070 unaffected trial participants were administered general risk factor and food frequency questionnaires. Conditional logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals. High parity and consumption of fresh fruits and vegetables were more strongly associated with a reduced risk of proliferative and atypical lesions than with nonproliferative conditions. For the fourth quartile of consumption versus the first, odds ratios for lesions diagnosed as nonproliferative, proliferative, and proliferative with atypia were 0.4 (95% confidence interval (CI): 0.2, 0.7), 0.2 (95% CI: 0.1, 0.4), and 0.1 (95% CI: 0.03, 0.5), respectively, for fruit intake and 0.6 (95% CI: 0.3, 1.1), 0.4 (95% CI: 0.2, 0.7), and 0.1 (95% CI: 0.1, 0.9), respectively, for vegetable intake. Reduced but nonsignificant risks in relation to soy products were observed for proliferative and atypical lesions. No single nutrient or botanical family was appreciably more strongly associated with proliferative conditions than with nonproliferative conditions, after results were controlled for total fruit and vegetable consumption. A diet rich in fruits and vegetables may reduce cellular proliferation in the mammary epithelium; this is one mechanism by which such a diet could reduce risk of breast cancer.

Diabetic fibrous mastopathy (DFM) is an uncommon lesion that may clinically mimic breast carcinoma. Routine mammographic and ultrasonographic features of this disease also mimic the those of malignant disease, making an accurate preoperative diagnosis difficult. Dynamic contrast-enhanced magnetic resonance imaging (MRI), however, reveals a homogeneous low-enhancement with a gradual and progressive course without a washout. A corresponding time intensity curve is related to benign lesions of low vascularity, and by being a potential criterion for making a differentiation between DFM and malignant processes, spares patients from excisional biopsy.

Objective: To compare the effects of five different hormone replacement regimens on fibrocystic mastopathy in postmenopausal women., Design: This was a randomized, prospective, clinical, case-control study., Methods: Two hundred and twelve women with benign cystic mastopathy were studied. The largest diameters of the breast cysts were measured using ultrasonography at study entry. Forty-eight women were randomized to the control group and did not take any medication. One hundred and sixty-four women were randomized to the following study groups. Group I (n = 46) were given conjugated estrogen (0.625 mg/day) and medroxyprogesterone acetate (5 mg/day) continuously. Group II (n = 22) were given only conjugated estrogens (0.625 mg/day) continuously; these were hysterectomized women. Group III (n = 32) were given transdermal estrogen (50 microg/day) and medroxyprogesterone acetate (5 mg/day) continuously. Group IV (n = 32) were given only transdermal estrogen (50 microg/day) continuously; these were also hysterectomized women. Group V (n = 32) were given tibolone (2.5 mg/day) continuously. Hormone therapy was continued for 12 months. Every 3 months the women were rescanned using ultrasonography to determine cyst diameters and examine characteristics such as internal echogenicity, and thickness and regularity of the cyst wall. Statistical assessment used Students' t test and Friedman analysis., Results: In the control group, there was no statistically significant change in cyst dimensions. However, tibolone was associated with a decrease in cyst dimensions which was statistically significant, but none of the other four hormone replacement therapy regimens caused any significant negative effect on the benign cystic mastopathy.