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Com a crescente urbanização e individualidade social há o aumento da criação com guarda responsável de animais de estimação, com principais exemplares os cães e gatos, este último como preferencial pelos tutores de forma ascendente nos últimos anos. Naturalmente os felinos podem ter até três gestações no período de um ano, com variação de um a nove filhotes em cada uma delas. Desta forma, a superpopulação destes animais ocorre de maneira exponencial. Esta característica, leva os proprietários a procurar por formas de contracepção para os animais. Dentre as formas existentes, destacam-se a ovariosalpingohisterectomia (OSH) e a contracepção hormonal. Os fármacos anticoncepcionais de maior utilização são os análogos sintéticos da progesterona, como, Acetato de Medroxiprogesterona (AMP), o Acetato de Megestrol e a proligestona. Porém, estes provocam efeitos negativos como hiperplasia endometrial cística, levando à piometra, hiperplasia mamária, resultando em tumores mamários, aborto, diabetes mellitus, dermatopatias e distúrbios comportamentais, portanto não é recomendado o seu uso nesta espécie. Foi realizado um levantamento de dados por meio de questionários, com proprietários de gatas levadas para atendimento clínico do Hospital Veterinário Universitário Jeremias Pereira da Silva da Universidade Federal do Piauí, com o objetivo de analisar quantitativamente os casos de animais com efeitos colaterais, de acordo com a raça e a idade, correlacionado ao uso de fármacos contraceptivos. Os dados obtidos se referem aos meses de março a maio de 2015. Todos os animais descritos neste estudo que apresentaram características patológicas fizeram a utilização de fármacos contraceptivos. Nos 2 casos de piometra encontrados a faixa etária de 4 anos (50%) e 8 anos (50%) foi observada, e todos (100%) os casos ocorreram em gatas Sem Raça definida (SRD). Dos 3 casos de neoplasia mamária, animais com 9 meses correspondem a 33,3%, 1 ano (33,33%) e 2 anos (33,33%) de idade, e todos (100%) eram SRD. Dos 2 casos de abortos, a faixa etária observada foi de 2 anos (50%) e de 3 anos (50%) de idade, e as raças afetadas foram SRD (50%) e siamesa (50%). Dos 2 casos de hiperplasia mamária observados. em gatas com 6 meses (50%) e 8 meses (50%) de idade, e a única raça acometida foi a SRD (100%). Conclui-se que o uso indiscriminado de fármacos contraceptivos ainda é frequente, assim como, é elevada a quantidade de animais que apresentam efeitos negativos ao seu uso.

optical breast spectroscopy (OBS) can predict breast density and can be used for risk assessment of breast cancer (BC). We have used this method to study the classification and prediction of breast hyperplasia. In this paper, the collected spectral data of clinical breast hyperplasia and normal human breast were classified and predicted by using machine learning Bayesian model, decision tree and k-nearest neighbor model (KNN). The research shows that the accuracy of machine learning algorithm for classification and diagnosis of breast hyperplasia can reach 93%. The combination of machine learning algorithm and practical medical diagnosis technology is of great significance, and it can be further developed to improve the efficiency and accuracy of clinical diagnosis.

The aim of this article is to present briefly new pathological entities which are recently increasingly commonly used in pathology reports, as well as to discuss their clinical consequences. The new WHO classification of breast diseases includes, inter alia , invasive carcinoma of no special type: this is not a specific entity, but rather a group of malignancies without specific features. The lobular hyperplasia group includes a classical variant and a pleomorphic variant of lobular carcinoma in situ, as well as atypical lobular hyperplasia. The ductal hyperplasia group, according to the current revision of the WHO classification of breast diseases, encompasses: typical (i.e. non-atypical) ductal hyperplasia, columnar cell change, columnar cell hyperplasia, atypical ductal hyperplasia. The mesenchymal breast hyperplasia group includes pseudoangiomatous stromal hyperplasia. We briefly discuss the above mentioned entities together with their respective clinical and therapeutic consequences.

A Hiperplasia mamária felina (HMF) é uma alteração não neoplásica, caracteriza pela proliferação celular do estroma do ducto das glândulas mamárias, comumente diagnosticada no Brasil. Tal alteração muitas vezes é causada pelo uso inadequado de progestágenos exógenos em gatos, que podem ser armazenados no organismo do animal, e sensibilizam as glândulas à proliferação exacerbada por estímulo hormonal. Um dos fatores associados aos casos recorrentes da HMF é a venda desses medicamentos em lojas que prestam serviço de venda de produtos veterinários, aplicados sem restrições e sem conhecimento da fisiologia felina, na tentativa de controle gestacional. A conscientização de tutores sobre os malefícios da aplicação sem critério de progestágenos e a estimulação dos mesmos para que optem por esterilização cirúrgica dos seus animais deve ser feita pelos médicos veterinários, a fim de que se evitem maiores complicações como neoplasia mamária, garantindo, portanto, maior bem estar da população felina. O objetivo dessa revisão é abordar aspectos epidemiológicos, fisiológicos e clínicos, e promover alusão ao uso indiscriminado de anticoncepcionais nessa espécie.

Breast cancer is estimated to be the leading cancer type among new cases in American women. Core biopsy data have shown a close association between breast hyperplasia and breast cancer. The early diagnosis and treatment of breast hyperplasia are extremely important to prevent breast cancer. The Mongolian medicine RuXian-I is a traditional drug that has achieved a high level of efficacy and a low incidence of side effects in its clinical use. However, for detecting the efficacy of RuXian-I, a rapid and accurate evaluation method based on metabolomic data is still lacking. Therefore, we proposed a framework, named the metabolomics deep belief network (MDBN), to analyze breast hyperplasia metabolomic data. We obtained 168 samples of metabolomic data from an animal model experiment of RuXian-I, which were averaged from control groups, treatment groups, and model groups. In the process of training, unlabelled data were used to pretrain the Deep Belief Networks models, and then labelled data were used to complete fine-tuning based on a limited-memory Broyden Fletcher Goldfarb Shanno (L-BFGS) algorithm. To prevent overfitting, a dropout method was added to the pretraining and fine-tuning procedures. The experimental results showed that the proposed model is superior to other classical classification methods that are based on positive and negative spectra data. Further, the proposed model can be used as an extension of the classification method for metabolomic data. For the high accuracy of classification of the three groups, the model indicates obvious differences and boundaries between the three groups. It can be inferred that the animal model of RuXian-I is well established, which can lay a foundation for subsequent related experiments. This also shows that metabolomic data can be used as a means to verify the effectiveness of RuXian-I in the treatment of breast hyperplasia.

The aim of the present study was to examine Ki-67 expression in tissue of luminal type breast cancer and to investigate the association between the Ki-67 expression level and clinicopathology of breast cancer. A total of 62 patients with breast cancer were included in the study group, whereas 30 patients undergoing a health check-up who were diagnosed with breast hyperplasia were included in the control group. Levels of Ki-67 expression in patients of the two groups were assessed using fluorescent quantitative polymerase chain reaction. The association between Ki-67 and the clinicopathology of the cancer was investigated by analyzing cancer cell proliferation and migration by reducing Ki-67 expression in the human MCF-7 cancer cell line. Compared with the controls, Ki-67 expression was significantly increased in the serum and cancer tissue of breast cancer patients (P

In this work, the clinical significance of changes in the activity of adenosine deaminase (ADA) and the content of polyamines in the blood plasma of cats with breast cancer was studied. There were examined 30 cats aged 1 to 20 years, operated on in veterinary clinics due to spontaneous neoplasms. Histological studies of surgical material were performed to establish nosological forms of the tumor. The results of the measurements showed that there were no significant differences between ADA activity in the blood plasma of cats diagnosed with invasive non-specific carcinoma and ADA activity in the blood of healthy animals. In the plasma of animals diagnosed with fibroadenomatous breast hyperplasia, ADA activity was reduced by 35% compared with the control group. The content of putrescine in the red blood cells of cats with benign neoplasms of the mammary gland (fibroepithelial hyperplasia) was statistically significantly increased 5 times compared with the control group. In malignant neoplasms of the mammary gland (invasive non-specific carcinoma, tubular cancer and fibrosarcoma), the content of putrescine and spermine in the blood significantly exceeded the control values by 60 and 10 times, respectively, compared with the control group. Thus, the data obtained indicate the possibility of using polyamines in order to improve the accuracy of diagnosis and treatment of cats with breast cancer. The determination of ADA activity in the blood plasma of cats with breast tumors in the early stages of cancer is not an informationally significant indicator as a tumor biomarker.

Introduction: Abnormal proliferation in the breast is clinically seen ranging from hyperplasia to atypia to in situ carcinomas (DCIS) to invasive cancers. Whether these states comprise points along an evolutionary continuum is a subject of debate, but has significant implications for prevention, prognosis, and treatment. Due to the length of time involved, tumor evolution is difficult to study in vivo and in vitro models. We hypothesize a continuum from hyperplasia to cancer can be demonstrated by examining patterns of accumulated mutations in tumors. We employ a previously developed computational model of ductal epithelial dynamics, the DEABM (1), to simulate and track accumulated mutations during the progression from a normal epithelial population through hyperplastic states to the development of invasive tumors Methods: Simulation experiments were performed using an expanded DEABM, which incorporates the functions of luminal and myoepithelial cells, their progenitors and fibroblasts. DNA damage can potentially disrupt 12 functional pathways regulated by oncogenes and tumor suppressors implicated in breast cancer (BRCA1, P53, E-cadherin, RUNX3, Myc, ER, TGF-b, MMP-3, EGFR, HER-2 and Telomerase). The expanded DEABM allows for sequential tracking of genetic lesions in each cell. 3,000 simulations in both wild-type (WT) and BRCA1-mutated states were run over 40 years of simulated menses. Cell populations were characterized as normal, hyperplastic or malignant based on quantitative cell expansion from baseline, as well as by mutational profiles, sequential order of mutations and ER status. Results: Tumor profiles approximated epidemiologic rates of cancer incidence and ER/HER2 status. 2.6 % of WT developed malignancy vs. 45.9% of BRCA1. WT tumors were 54% ER+/HER2-, 17% ER+/HER2+, 6% ER-/HER2+ and 22% ER-/HER2-. BRCA1 tumors were 29% ER+/HER2-, 7% ER+/HER2+, 13% ER-/HER2+ and 50% ER-/HER2-. Hyperplastic populations carried more mutations than non-hyperplastic populations (p>.01) and were more likely to carry mutations in telomerase, E-cadherin and genes related to ER expression (TGFB, RUNX3, p Conclusion: The DEABM generates diverse tumors that express tumor markers consistent with epidemiologic data. The DEABM also generates non-invasive, hyperplastic populations, analogous to atypia and/or DCIS, via mutations to genes known to be present in hyperplastic lesions and early mutations in breast cancers. The results demonstrate that agent-based models are well-suited to studying tumor evolution through stages of carcinogenesis and have the potential to be used to develop prevention and treatment strategies. Ref: Chapa J, et al. "Examining the Pathogenesis of Breast Cancer Using a Novel Agent-Based Model of Mammary Ductal Epithelium Dynamics." PloS one 8.5 (2013). Citation Format: Joaquin Chapa, Gary An, Swati A Kulkarni. Demonstration of the evolutionary dynamics of the progression from breast hyperplasia to cancer using the duct epithelial agent based model (DEABM) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-08-03.

The objective of the present study was to investigate a comparative estimation screening method of prostate specific antigen levels in serum samples with immunohistochemistry results for analysis expression of prostate specific antigen in female breast tissues at benign breast hyperplasia and breast cancer. This study was applied on 65 women suffering from breast cancer, 31 of them have benign breast hyperplasia and 34 have malignant breast cancer. Each group was divided into 2 subgroups, pre and postmenopause, both subgroups were compared with 15 normal cases to assess serum and tissue PSA in benign and malignant patients in pre and post menopause state by immunoradiometric assay in blood and immunohistochemistry in tissue. No significant difference in serum Total PSA concentration between any of the studied cases. However, there were different variations in the distribution of PSA in the breast tumor tissue, with complete absence of PSA in the tissue samples of the malignant in postmenopausal patients. In conclusion, PSA presence in benign breast hyperplasia in either serum or tissue may show clinical value regarding the diagnosis and prognosis of the disease.

Uncontrolled proliferation is one of the hallmarks of breast cancer. We have previously identified the human Ecd protein (human ortholog of Drosophila Ecdysoneless, hereafter called Ecd) as a novel promoter of mammalian cell cycle progression, a function related to its ability to remove the repressive effects of Rb-family tumor suppressors on E2F transcription factors. Given the frequent dysregulation of cell cycle regulatory components in human cancer, we used immunohistochemistry of paraffin-embedded tissues to examine Ecd expression in normal breast tissue versus tissues representing increasing breast cancer progression. Initial studies of a smaller cohort without outcomes information showed that Ecd expression was barely detectable in normal breast tissue and in hyperplasia of breast, but high levels of Ecd were detected in benign breast hyperplasia, ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDCs) of the breast. In this cohort of 104 IDC patients, Ecd expression levels showed a positive correlation with higher grade (P = 0.04). Further analyses of Ecd expression using a larger, independent cohort (954) confirmed these results, with a strong positive correlation of elevated Ecd expression with higher histological grade (P = 0.013), mitotic index (P = 0.032), and Nottingham Prognostic Index score (P = 0.014). Ecd expression was positively associated with HER2/neu (P = 0.002) overexpression, a known marker of poor prognosis in breast cancer. Significantly, increased Ecd expression showed a strong positive association with shorter breast cancer specific survival (BCSS) (P = 0.008) and disease-free survival (DFS) (P = 0.003) in HER2/neu overexpressing patients. Taken together, our results reveal Ecd as a novel marker for breast cancer progression and show that levels of Ecd expression predict poorer survival in Her2/neu overexpressing breast cancer patients. Electronic supplementary material The online version of this article (doi:10.1007/s10549-011-1946-8) contains supplementary material, which is available to authorized users.

RuXian-I has traditionally been used as a remedy for breast hyperplasia in the Inner Mongolia Autonomous Region of China. As a first step toward the investigation of biomarkers associated with RuXian-I treatment, a proteome-wide analysis of rat breast tissue was conducted. First, rat breast hyperplasia was induced by injection of estradiol and progesterone. After treatment with RuXian-I, there is a marked decrease in the hyperplasia, as can be shown by decreases in the nipple diameter and the pathological changes in breast. Subsequently, we used an approach that integrates size-based 2D-DIGE, MALDI-TOF/TOF-MS, and bioinformatics to analyze data from the control group, the model group and the RuXian-I treatment group. Using this approach, seventeen affected proteins were identified. Among these, 15 (including annexin A1, annexin A2, superoxide dismutase [Mn], peroxiredoxin-1, translationally-controlled tumor protein and a B-crystallin) were significantly up-regulated in the model group and down-regulated upon treatment with RuXian-I, and two (Tpil protein and myosin-4) have the opposite change trend. The expression of annexin A1 was confirmed using immunohistochemistry. The expression of superoxide dismutase (SOD) activity was confirmed biochemically. These results indicated that RuXian-I treats rat breast hyperplasia through regulation of cell cycle, immune system, metabolic, signal transduction, etc. The differential expressions of these proteins (annexin A1, superoxide dismutase [Mn], alpha B-crystallins and translationally controlled tumor protein, among others) were associated with occurrence and metastasis of breast cancer. These findings might provide not only far-reaching valuable insights into the mechanism of RuXian-I action, but also leads for prognosis and diagnosis of breast hyperplasia and breast cancer.

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is one of the most frequently mutated human tumor suppressor genes. The present study aims to investigate the role of PTEN mutation in breast carcinogenesis by analyzing PTEN mutation spectrum and the protein expression in breast cancers, adjacent hyperplastic lesions, benign breast lesions and normal breast tissues. All 9 exons of PTEN gene were amplified by PCR with DNA extracted from 50 of human breast cancers and corresponding adjacent breast hyperplasia tissues, adjacent normal breast tissues, as well as 50 breast benign lesions residing in or around Yunnan, China, respectively. PCR products were then sequenced for mutation screening. And we also proved the effect of mutations on the expression of PTEN protein by immunohistochemistry. PTEN mutations were detected in 11 of 50 (22%) breast cancers and 4 of 50 (8%) adjacent ductal hyperplasia, all of which were atypical ductal hyperplasia and same PTEN mutation were detected in the corresponding cancer tissues. No PTEN mutation was detected in all adjacent normal breast tissues and 50 cases of breast benign lesions. The mutation sites concentrated at exon 3, 4, 5 and 7; no mutation was detected in exon 1, 2, 6, 8, or 9 and splicing sites of all introns. The hottest mutation spots were exon 5 with missense mutations. Immunohistochemical analysis showed that 24 of 50 (48%) breast cancers and 6 of 50 (12%) adjacent breast hyperplasia demonstrated negative immuno-staining of PTEN (loss of PTEN protein expression). All the 4 adjacent breast tissues harbored PTEN mutations and 9 of 11 breast cancers with PTEN mutation were loss of PTEN expression. Statistical analysis revealed that PTEN gene mutations were correlated with the PTEN expression. The incidence of PTEN mutations is relatively high in patients with sporadic breast cancer in the region of Yunnan, China and exists at the early stage of breast cancer development. The PTEN mutations have significant effect on the expression silencing of PTEN protein indicating the important role of PTEN mutation in carcinogenesis of breast cancers.

BACKGROUND: The precise timing of the angiogenic switch and the role of angiogenesis in the development of breast malignancy is currently unknown. METHODS: Therefore, the expression of CD31 (pan endothelial cells (ECs)), endoglin (actively proliferating ECs), hypoxia-inducible factor-1 (HIF-1alpha), vascular endothelial growth factor-A (VEGF) and tissue factor (TF) were quantified in 140 surgical specimens comprising normal human breast, benign and pre-malignant hyperplastic tissue, in situ and invasive breast cancer specimens. RESULTS: Significant increases in angiogenesis (microvessel density) were observed between normal and benign hyperplastic breast tissue (P

Purpose The NOEY2 gene mutations and protein expression in human breast cancers, adjacent breast tissues and breast benign lesions were analysed to explore the potential correlation between the mutation spectrum and breast cancer development and progression. Experimental design The promoter, exon and intron regions of NOEY2 gene were amplified by polymerase chain reaction (PCR) with DNA extracted from 50 human breast cancer and corresponding adjacent breast tissues as well as 50 breast benign lesions, respectively. The PCR products were then sequenced and analysed. The effect of mutations on the expression of NOEY2 protein by immunohistochemistry were proven as well. Results Twenty-one of 50 (42%) breast cancer mutations were identified in promoter (11 cases) and exon 2 (seven cases on untranslation region and three on coding region) and 17 of 50 (34%) adjacent breast tissues (all were atypical hyperplasia lesions) occurred mutations, including six promoter mutations and 11 exon 2 changes (10 cases on untranslation region and one on coding region). Interestingly, the mutations were identified in both breast cancers and the corresponding adjacent breast tissues collected from the same patient in seven of them. No mutation was identified in all benign breast tissues. Immunohistochemical analysis showed that two of 17 mutational adjacent breast tissue samples were NOEY2 immunoreaction negative, and in all 21 mutations of breast cancers five cases were of loss of NOEY2 expression. All mutations with immunoreaction negative factor were located at promoter and/or exon 2 coding region. NOEY2 gene mutations were not correlated with patient ages, histological types, tumour sizes, histological grades, clinical stages, axillary lymph node metastases or with the condition of hormone receptor (ER, PR) expression and HER2 amplification. Conclusions The mutations of human NOEY2 were identified in human breast cancers and the corresponding adjacent breast tissues. The hot mutation spots were its promoter and exon 2 regions, and those occurring at the exon2 coding region and part of the promoter may alter the expression of NOEY2. The presence of NOEY2 mutations in human breast cancer and early-stage lesions indicates that NOEY2 mutations may be partly associated with breast tumourigenesis.

The cyclooxygenase-2 (COX-2) enzyme, which is induced by inflammatory and mitogenic stimuli, plays a protumorigenic role in several human cancers. COX-2 is overexpressed in invasive and in situ breast cancers. Atypical hyperplasia in breast tissue, although benign, is associated with a high risk of breast cancer. We investigated whether COX-2 overexpression in atypical hyperplasia is associated with the risk of subsequent breast cancer.COX-2 expression was assessed immunohistochemically in archival sections from 235 women with atypia whose biopsy specimens were obtained at the Mayo Clinic from January 1, 1967, through December 31, 1991. COX-2 expression was scored as 0 (negative), 1+ (weak), 2+ (moderate), or 3+ (strong). Risk factor information and follow-up for breast cancer events were obtained via a study questionnaire and the medical records. All statistical tests were two-sided.Forty-one (17%) of the 235 women developed breast cancer during a median follow-up of 15 years. Moderate (category 2+) or strong (category 3+) COX-2 expression was identified in 71 (30%) and 34 (14%) of the 235 samples, respectively. The risk for developing breast cancer, relative to a control population (the Iowa Surveillance, Epidemiology, and End Results registry), increased with increasing COX-2 expression (relative risk [RR] = 2.63, 95% confidence interval [CI] = 1.56 to 4.15, for those with negative or weak COX-2 expression; RR = 3.56, 95% CI = 1.94 to 5.97, for those with moderate expression; and RR = 5.66, 95% CI = 2.59 to 10.75, for those with strong expression; P = .07). Overexpression of COX-2 was statistically significantly associated with the type of atypia (lobular vs ductal, P.001), number of foci of atypia in the biopsy (P = .02), and older age at time of biopsy (45 years, P = .01).COX-2 appears to be a biomarker that further stratifies breast cancer risk among women with atypia and may be a relevant target for chemoprevention strategies.

The main disadvantage of Vacuum Assisted Breast Biopsy (VABB) is the probability of underestimating atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS). This study evaluates a modified way of performing VABB.266 women with microcalcifications graded BI-RADS 34 underwent VABB (11G) on the Fischer's table. 133 women were allocated to the "standard" protocol and 24 cores were obtained (1 offset-main target and one additional offset). 133 women were randomly allocated to the "extended" protocol and 96 cores were excised (one offset- main target and 7 peripheral offsets). A preoperative diagnosis was established, and the removed volume was calculated. When precursor or malignant lesions were diagnosed, open surgery was performed. A second pathologist, blind to the preoperative results and to the protocol made the postoperative diagnosis. The discrepancy between preoperative and postoperative diagnoses was evaluated.When the standard protocol was applied, the underestimation rate for preoperative ADH, lobular neoplasia (LN), DCIS was 16.7%, 50% and 14.3% correspondingly. In the extended protocol, no underestimation was present in LN, ADH, but the underestimation rate for DCIS was 6.3%. In the extended protocol, no precursor/malignant tissue was left after VABB in all ADH cases, in 87.5% of LN cases, in 73.3% of DCIS, and in 50% of invasive carcinomas. The volume excised was 2.33 +/- 0.60 cc and 6.14 +/- 1.30 cc for the standard and the extended protocol, respectively. The rate of hematoma formation did not differ between the two protocols.This recently introduced, "extended" way of performing VABB in microcalcifications safely minimizes the underestimation rate, which may lead to a modified management of ADH lesions.

To detect the expressions of E-cadherin, α-catenin and β-catenin and analyze the relationship between E-cadherin-catenin adhesion complex and clinicopathological features in breast cancer. The expressions of E-cadherin, α-cadherin and β-catenin in specimens of 54 breast cancer, 21 normal breast tissues around tumor, 15 breast hyperplasia of usual type and 15 breast atypical hyperplasia were detected by immunohistochemical method. In 21 normal breast tissues, E-cadherin and α-catenin were expressed on cell membrane of ductal and acinic cells, showing cellular contour and border among cells. The staining character of the three proteins in breast hyperplasia of usual type was the same as that in normal breast tissue. In breast atypical hyperplasia, the abnormal expression rates of E-cadherin, α-catenin and β-catenin were 6.7%, 13.3% and 26.7%, respectively. The total abnormal expression rate of E-cadherin-catenin complex was 33.3%. In breast cancer, the abnormal expression rates of E-cadherin, α-catenin and β-catenin were 51.9%, 63.0% and 61.1%, respectively. The total abnormal expression rate of E-cadherin-catenin complex was 88.9%. Abnormal expression of E-cadherin and α-catenin were significantly correlated with histological grade. Abnormal expressions of α-catenin and β-catenin were significantly correlated with TNM staging, axillary lymph nodes metastasis and postoperative distant metastasis. Abnormal expression of E-cadherin-catenin complex was correlated with TNM staging, histological grade and axillary lymph nodes. Abnormal expression of β-catenin was negatively correlated with expression of HER-2. COX multiple factor analysis showed that E-cadherin or α-catenin or β-catenin was not independent prognostic indicator. Abnormal expressions of E-cadherin, α-catenin and β-catenin frequently occur in breast cancer. Abnormal expression of E-cadherin-catenin complex is correlated with differentiation disturbance and metastasis. Combined measurement of E-caherin, α-catenin and β-catenin may improve accuracy and sensitivity of predicting metastasis and prognosis of breast cancer.

It remains unclear whether hyperplastic breast lesions, especially with atypia, are cancer precursors or markers of increased cancer risk. Quantified comparisons of genomic alterations in coexisting lesions could address this question. Therefore, we examined allele imbalance (AI), also known as loss of heterozygosity (LOH), at 20 microsatellite markers on nine chromosome arms, in DNA from 106 samples microdissected from 17 randomly selected cancer-containing breast specimens: 13 simple (DH) and 45 atypical ductal hyperplastic (ADH) lesions, 30 in situ (DCIS) and 18 invasive ductal carcinomas (IDC). Data were analysed using regression models and generalized estimating equations. We found that AI increased as histology became more aberrant and varied with histology across the chromosome arms (p

Dietary phytosterol supplements are readily available to consumers since they effectively reduce plasma low-density lipoprotein cholesterol. Several studies on cell cultures and xenograft mouse models suggest that dietary phytosterols may also exert protective effects against common cancers. We examined the effects of a dietary phytosterol supplement on tumor onset and progression using the well-characterized mouse mammary tumor virus polyoma virus middle T antigen transgenic mouse model of inherited breast cancer. Both the development of mammary hyperplastic lesions (at age 4 weeks) and total tumor burden (at age 13 weeks) were reduced after dietary phytosterol supplementation in female mice fed a high-fat, high-cholesterol diet. A blind, detailed histopathologic examination of the mammary glands (at age 8 weeks) also revealed the presence of less-advanced lesions in phytosterol-fed mice. This protective effect was not observed when the mice were fed a low-fat, low-cholesterol diet. Phytosterol supplementation was effective in preventing lipoprotein oxidation in mice fed the high-fat diet, a property that may explain - at least in part - their anticancer effects since lipoprotein oxidation/inflammation has been shown to be critical for tumor growth. In summary, our study provides preclinical proof of the concept that dietary phytosterols could prevent the tumor growth associated with fat-rich diet consumption. © 2013 Elsevier Inc.

Benign breast hyperplasia is a diseases of civilization associated in women with hormonal disorders, estrogen dominance syndrome. Risk of developing breast cancer for women with proliferative forms of benign breast disease increased tenfold. Absolutely all patients seek medical attention, regardless of pathology, must undergo breast examination and obtain recommendations for the prevention and the multiplicity of diagnostic tests. An important role in the pathogenesis of benign breast hyperplasia plays an increase prolactin levels. Hyperprolactinemia is a frequent cause of menstrual and generative dysfunctions, as well as benign breast hyperplasia, which negatively affects the quality of women life. Quite often there is not a permanent but temporary (latent or hidden) increase prolactin secretion. Occasional bursts of prolactin levels, combined with hyperestrogenemia cause bloating, breast tenderness (mastalgia). Hyperprolactinemia induced menstrual dysfunction causes abnormal steroidogenesis in the ovaries, which also exacerbates the morphological and functional abnormalities in the mammary glands, promotes dishormonal breast diseases and increases the risk of breast cancer. Due to the increase of cancer incidence in all countries is increased emphasis on early tumors diagnosis and prevention. Special nutrition and various diets are considered as one of the variants of the anti-tumor protection. Numerous studies in recent years devoted phytonutrients – substances of plant origin. Phytopreparation that can be used in these disorders is Epigalin Brest® that contained indole-3-carbinol, epigallocatechin-3-gallate and Vitex agnus castus extract. Indole-3-carbinol and epigallocatechin-3-gallate are biologically active substances with a well-deserved popularity among clinicians in Europe and the United States. Herbal drug Epigalin Brest® regulates the metabolism of estrogen by blocking the synthesis of its “aggressive” forms, reduces the level of prolactin, inhibits the abnormal proliferation in hormone-dependent organs (mammary gland) and tissues of the reproductive system. Also Epigalin Brest® has antiproliferative effects.

CREB-2, also known as ATF-4, belongs to the CREB proteins, a family of transcription factors phosphorylated at serine residues by protein kinase A (PKA). This family is known to stimulate the transcription of genes containing CRE elements. Recently, some studies have demonstrated elevated CREB-2 expression in certain tumor types, including breast carcinoma, compared to their corresponding non-tumor tissues. However, the expression and clinical significance in malignant tumors, including breast carcinoma, of p-CREB-2 (ser 245), a phosphorylated form of the CREB-2 protein at serine 245 site, which is believed to be an active type of this protein, have not been clearly documented. In the present study, we investigated the expression of p-CREB-2 (ser 245) in a group of tumor and non-tumor breast tissues, including normal breast epithelia, hyperplasia, dysplasia, carcinoma in situ and infiltrating carcinoma of the breast using tissue microarray and immunohistochemistry (IHC). p-CREB-2 (ser 245) immunostaining was detected in the nucleus and cytoplasm of these tissues. Compared to normal breast epithelia and breast hyperplasia (total positive rate 13.3%), there was increased expression of p-CREB-2 (ser 245) in dysplasia, carcinoma in situ (total positive rate 35.7%) and infiltrating carcinoma of the breast (total positive rate 60.0%) (p

Estrogens play a key role in the genesis and progression of breast cancer, activating two estrogen receptors, alpha and beta (ERα and ERβ). We have previously observed that ERα methylation occurs in high frequency and may be one of the mechanisms of ERα expression silence in a subset of Chinese sporadic breast cancers. However, the ERβ promoter methylation status and the relationship between clinicopathological characteristics and ERβ methylation in sporadic breast cancer are still unknown, especially in Chinese women. This study acted to determine the methylation status of the ERβ promoter and its correlation with clinicopathological features of sporadic breast cancers in Chinese women, and lay a foundation for the management of breast cancer. In total, 178 cases with sporadic breast cancers were enrolled in the study. ERβ methylation was determined using a methylation-specific polymerase chain reaction (MSP). In general, ERβ promoter methylation was found in 44.9% (80/178) of breast tumor samples, significantly higher than the benign breast hyperplasia (44.9% vs. 14.3%, X(2) = 4.986, P = 0.026). A total of 58% (40/69) of ERβ-negative tumors got methylation compared with 36.7% (40/109) of ERβ-positive cases being methylated (X(2) = 7.728, P = 0.005). The levels of ERβ protein expression diminished with the frequency of ERβ methylation (r = -0.249, P < 0.0001). In addition, we observed a strong correlation between ERα promoter and ERβ promoter methylation (odds ratio 2.054, 95% confidence interval 1.086-3.886, P = 0.026), and the triple-negative tumors showed a significantly higher methylation rate of ERβ. This study presents, for what we believe to be the first time, that ERβ methylation is also a frequent event in breast cancer and maybe also one of the mechanisms of ERβ expression silence in a subset of Chinese sporadic breast cancers. Epigenetic alteration of the ERβ gene may play an important role in the pathogenesis of breast cancer.

Obesity has been associated with abnormally high expression of the enzyme aromatase in the breast, increased local estrogen production, and predisposition to breast hyperplasia and cancer. Increased adiposity in postmenopausal women may trigger signaling pathways that induce aromatase expression. In breast adipose fibroblasts, increased TNF production may induce the distal aromatase promoter, whereas increased local PGE(2) production may induce the proximal promoter region. We review here the mechanisms that control aromatase gene expression in breast adipose tissue, and the paracrine interactions between malignant breast epithelial cells and the surrounding adipose fibroblasts. Systematic characterization of these signaling pathways will facilitate the identification of potential drug targets to selectively reduce aromatase expression and excessive estrogen production, with therapeutic benefit.

Expressions of Notch1 and Cyclin D1 were analysed by immunohistochemical method in the specimens of normal mammary tissue, usual hyperplasia, atypical hyperplasia, cancer in situ, and invasive cancer tissue, which were obtained from the patients operated due to some kind of breast disease. We observed an evidently decreased Notch1 and increased cyclin D1 expression respectively from normal tissue to invasive cancer, and a negative correlation was drawn between Notch1 and Cyclin D1. No correlation was found between Notch1 expression and any clinicopathologic parameter, but there was positive correlation between the Cyclin D1 expression and ER. This indicated the inhibiting function of Notch1 and promoting function of Cyclin D1 in proliferating process of mammary ductal tissue. From hyperplasia to cancer, there is a continus and sequential process, which suggest an intimate relationship between mammary hyperplasia and breast cancer. Key words-mammary ductal hyperplasia; invasive mammary cancer; Notch1; Cyclin D1; immunohistochemistry

Previous studies have shown the chromosomal alterations in usual ductal hyperplasia (UDH), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) in the breast with bilateral ductal hyperplasia or adjacent to invasive ductal carcinoma (IDC). However, the role of UDH as a putative precursor of breast IDC is not clear and has not been fully addressed. The aim of this study was to clarify the role of UDH in breast carcinoma pathogenesis. To investigate chromosomal imbalances and commonality, samples of pure unilateral UDH (n=20) were obtained by laser capture microdissection and analyzed by comparative genomic hybridization. Other ductal lesions, including ADH (n=2), high-grade DCIS (n=3), and grade III IDC (n=5), were assessed at the same time for comparison. The mean values of alteration were 1.95 (39/20) in UDH, 9.5 (19/2) in ADH, 11.0 (33/3) in DCIS and 18.2 (89/5) in IDC, respectively. Some common predisposition regions for the deletions were at chromosomes 1p36-pter, 13q11-14, and 16q11-23, while the high frequency amplification regions were 1q31-qter, 3p21-pter, 6p21-pter, 11q11-14, 12q11-qter, 13q21-qter, 16p12-pter, 17q12-22, and 20q. The genetic abnormalities in the spectrum of breast ductal hyperplasia revealed that the deletion of DNA copy in UDH was the lowest, and gradually increased in the lineages of ADH, DCIS and IDC. Results showed that a significant portion of UDH shares common genetic alterations with ADH, DCIS and IDC, indicating UDH as a precursor of invasive breast ductal carcinoma.

BACKGROUND. Atypical lobular hyperplasia (ALH) is associated with a 10% to 20% risk of subsequent invasive carcinoma, primarily in the ipsilateral breast. Nottingham grading, special tumor types, and survival after invasive cancer diagnosis were analyzed consistently for the first time. METHODS. A longitudinal follow-up study of 252 women who underwent 261 benign surgical biopsies between 1950 and 1985 with a diagnosis of ALH was undertaken. Subsequent invasive breast cancers were graded and subtyped based on histologic features and the cohort assessed for cancer survival. RESULTS. Forty-eight (19%) women developed invasive breast cancer at an average of 15.1 years. Twenty (42%) of the tumors were special subtype tumors with good prognosis. By an average of 13 years after invasive cancer diagnosis, 2 (10%) of 20 women with special type and variant tumors had died of breast cancer, compared with 9 (32%) of 28 women with tumors of no special type (24 tumors) or an unknown type (4 tumors). Only 1 patient with a tumor of low Nottingham grade died of breast cancer. CONCLUSIONS. ALH is a nonobligate cancer precursor associated with a moderate risk of breast cancer and predicts that later cancers are associated with overall excellent survival. Nearly half of the subsequent cancers show classic or variant patterns of special types with a good prognosis and the majority are of low or intermediate combined histologic grade. Treatment of women with ALH should be influenced by their modest elevation in breast cancer risk and the good prognosis and low mortality of many of these cancers. Cancer 2006. © 2006 American Cancer Society.

Laminin is a glycoprotein of the basement membrane (BM), involved in a variety of normal and pathological cellular events including tumour invasion and metastasis. Cells bind laminin through different types of receptor. The 67-kD laminin receptor (67LR) is a cell-surface protein which binds laminin with high affinity. 67LR expression has been shown to increase in neoplastic cells, compared with normal tissues, and 67LR seems to play an important role during the first steps of neoplastic progression. In this study, 67LR expression was analysed during the morphological phases of breast cancer progression from normal tissue to invasive carcinoma. A total of 506 formalin-fixed, paraffin-embedded normal breast structures and lesions were stained by immunohistochemistry using the MLuC5 monoclonal antibody, which is specific for 67LR. The results show that in normal breast and in any kind of breast lesion, myoepithelial and endothelial cells express 67LR. While 67LR is not seen in the epithelium of normal breast, cysts, adenosis, and benign tumours, it is expressed in the epithelial cells of several hyperplasias and carcinomas in situ, both ductal and lobular, as well as in all invasive carcinomas. The 67LR-positive cell subpopulation expands from hyperplastic lesions to invasive carcinoma, suggesting that 67LR could be related to the induction and progression of breast cancer. © 1997 John Wiley & Sons, Ltd.

Purpose: The need for surgical excision in patients with ultrasound-guided core needle biopsy (CNB)-diagnosed atypical ductal hyperplasia (ADH) remains an issue of debate. The present study sought to validate a scoring system (the U score, for underestimation) that we have previously developed for predicting malignancy in CNB-diagnosed ADH. Methods: The study prospectively enrolled 85 female patients with CNB-diagnosed ADH who underwent subsequent surgical excision. Underestimation was defined as a surgical specimen having malignant foci. Results: The overall underestimation rate was 37% (31/85). Multivariate analysis showed that a clinically palpable mass, microcalcification on imaging, size > 15 mm and a patient age of ≥ 50 years were independently associated with underestimation. When applied to the scoring system, the validation score was significant (p< 0.001; area under the curve, 0.852). No patient with a U score < 3.5 had an underestimated lesion. Conclusion: The present study successfully validated the efficacy of our scoring system for predicting malignancy in CNB-diagnosed ADH. A U score of ≤ 3.5 indicates that surgical excision may not be necessary.

Breast core needle biopsy (CNB) is an established method for diagnosing benign and malignant breast disease and CNB is widely used in daily practice. However, CNB samples only part of a lesion, and this can be the reason for an inaccurate diagnosis.(1) This size limitation of CNB gives rise to important diagnostic problems because one of the important factors for making the differential diagnosis between atypical ductal hyperplasia (ADH) and lowgrade ductal carcinoma in situ (DCIS) is the size of the lesion.(2,3) Previous studies have reported that ADH in a CNB showed significant discordance in the subsequent surgical excision specimens for which 33-87% demonstrated ductal carcinoma such as DCIS and invasive ductal carcinoma (IDC).(4-11) Therefore, surgical excision is presently recommended when ADH is diagnosed in a CNB. Investigations to determine the factors that are predictive of more advanced lesions in surgical excision specimens when ADH was diagnosed in the CNB have suggested cytologic atypia,(11) more than 4 foci (7) and micropapillary architecture (7), yet consistent results were not demonstrated. The purpose of this study was to identify the predictive factors that suggest the diagnosis of ductal carcinoma in the subsequent surgical excision specimens when ADH is diagnosed in a CNB.