Comparative genomic hybridization analysis of benign and invasive male breast neoplasms

Comparative genomic hybridization (CGH) analysis was performed for the identification of chromosomal imbalances in two benign gynecomastias and one malignant breast carcinoma derived from patients with male breast disease and compared with cytogenetic analysis in two of the three cases. CGH analysis demonstrated overrepresentation of 8q in all three cases. One case of gynecomastia presented gain of 1p34.3similar topter. 11p14similar toq12. and 17p11.2similar toqter, and loss of 1q41similar toqter and 4q33similar toqter. The other gynecomastia presented del(1)(q41) as detected by both cytogenetic and CGH analysis. CGH analysis of the invasive ductal carcinoma confirmed a gain of 17p11.2similar toqter previously detected by cytogenetic analysis. These regions showed some similarity in their pattern of imbalance to the chromosomal alterations described in female and male breast cancer. (C) 2002 Elsevier B.V. All rights reserved.

Tempo para acesso ao tratamento do câncer de mama no Distrito Federal, Brasil Central

PURPOSE: To analyze the time between the first symptom and treatment in patients treated for breast cancer in public hospitals in the Federal District. METHODS: This was a cross-sectional analysis. We interviewed 250 women diagnosed with breast cancer treated in six hospitals of the State Department of Health of the Federal District from November 2009 to January 2011. The time intervals studied were the time between the detection of the symptoms and treatment subdivided into intervals until and after the first medical appointment. The variables were: age, menopausal status, color, educational level, average monthly household income, origin, reason for the initial consultation, staging, tumor size, laterality, metastasis to axillary lymph nodes, neoadjuvant chemotherapy, and type of surgery. The Mann-Whtney test was used to assess the association of these variables with the time intervals until treatment. RESULTS: The mean age was 52 years, with a predominance of white women (57.6%), from the Federal District (62.4%), with a family income of up to 2 minimum wages (78%), and up to four years of schooling (52.4%). The staging of the disease ranged from II to IV in 78.8% of the women. The time between the first symptom and treatment was 229 days (median). After detection of the first symptom, 52.9% of the women attended a consultation within 30 days and 88.8% took more than 90 days to start treatment. Women with elementary school education had a greater delay to the start of treatment (p=0.049). CONCLUSIONS: There was a significant delay to start treatment of women with breast cancer in public hospitals of the Federal District, suggesting that efforts should be made to reduce the time needed to schedule medical appointments and to diagnose and treat these patients.

Human breast tumor slices as an alternative approach to cell lines to individualize research for each patient

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

An unusual case of malignant cystosarcoma phyllodes of the breast

A unusually large tumor of the left breast diagnosed as a cystosarcoma phyllodes with multiple malignant sarcomatous changes of the stroma, consisting of liposarcoma, myxoid fibrosarcoma, anaplastic, and giant cell sarcoma is described. The weight of 6200 g (13.5 lb) seems to be the largest so far presented in the literature reviewed by the authors. © 1986.

Necrotizing soft tissue infection of the breast: Case report and literature review

Background: Necrotizing soft tissue infection (NSTI) is characterized by progressive infectious gangrene of the skin and subcutaneous tissue. Its treatment involves intensive care, broad-spectrum antibiotic therapy, and full debridement. Methods: We present two cases of NSTI of the breast, adding these cases to the 14 described in the literature, reviewing the characteristics and evolution of all cases. Case Report: On the fourth day after mastectomy, a 59-year-old woman with ulcerated breast cancer developed Type I NSTI caused by Pseudomonas aeruginosa, which had a favorable evolution after debridement and broad-spectrum antibiotics. The second patient was a 57-year-old woman submitted to a mastectomy and axillary dissection, who had recurrent seromas. On the 32nd post-operative day, after a seroma puncture, she developed Type II NSTI caused by β-hemolytic streptococci. She developed sepsis and died on the tenth day after debridement, intensive care, and broad-spectrum antibiotics. The cases are the first description of breast NSTI after mammary seroma aspiration and the first report of this condition caused by P. aeruginosa. Conclusion: Necrotizing soft tissue infection is rare in breast tissue. It frequently is of Type II, occurring mainly after procedures in patients with breast cancer. The surgeon's participation in controlling the focus of the infection is of fundamental importance, and just as important are broad-spectrum antibiotic therapy and support measures, such as maintenance of volume, correction of electrolytic disorders, and treatment of sepsis and septic shock. Once the infection has been brought under control, skin grafting or soft tissue flaps can be considered. The mortality rate in breast NSTI is 18.7%, all deaths being in patients with the fulminant Type II form. Surgical oncologists need to be alert to the possibility of this rare condition. © 2012, Mary Ann Liebert, Inc.

Polymorphisms of estrogen receptor-α gene in Brazilian women with high breast density after menopause

The association of genetic polymorphism in the estrogen receptor alpha (ERα) gene and risk for diseases including breast cancer (BC) has been the subject of great interest. Objective: Checking on women with high breast density after menopause, the frequency of the Pvull and Xbal polymorphisms of the ERα gene and the correlation between them and the known risk factors for breast cancer. Method: Observational study with 308 women between 45 and 65 years old with high breast density, without hormonal therapy, menstruation for a year or more, breast and ovarian cancer history. It was characterized in clinical history and physical examination: menarche, menopause, parity, family history of BC, smoking, alcohol intake and body mass index. Results: The allelic and genotypic frequencies for ERα-Pvull and Xbal: p=43.99%; p=56.01%; pp=32.14%; Pp=47.73% and PP=20.13%; X=41.56%; x=58.44%; xx=33.44%; Xx=50.00% and XX=16.56%, respectively. The most frequent risk factors for BC: menarche before 12 years old (35.38%), nulliparity or first child after 28 years old (41.66%), family history of BC (19.16%) and overweight/obesity (62.01%). Conclusion: Allelic and genotypic distribution similar to literature. The risk factors for BC were more prevalent in women with high breast density but without significant associations with these polymorphisms. © 2013 Informa UK Ltd. All rights reserved.

Influence of estradiol and triiodothyronine on breast cancer cell lines proliferation and expression of estrogen and thyroid hormone receptors

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influência da terapêutica hormonal prévia sobre os indicadores de prognóstico do câncer de mama em mulheres na pós-menopausa

OBJETIVO: avaliar a influência da terapêutica hormonal (TH) prévia sobre alguns indicadores de prognóstico do câncer de mama, em pacientes na pós-menopausa. MÉTODOS: estudo transversal por meio da aplicação de questionários e levantamento de prontuários. Foram entrevistadas 157 pacientes com diagnóstico de câncer de mama na pós-menopausa, registrando-se dados clínicos, antecedentes pessoais e familiares, uso de TH e mamografias. Nos prontuários foram obtidas informações sobre o câncer de mama quanto ao diâmetro do tumor, tipo de cirurgia e estudo imuno-histoquímico. Para a estatística empregou-se ANOVA e teste do chi2. RESULTADOS: 38,2% das pacientes eram ex-usuárias de TH e 61,8% não usuárias. O tempo médio de uso da TH foi de 3,7±3,6 anos. As ex-usuárias eram de menor faixa etária e com menor tempo de menopausa quando comparadas às não usuárias (p<0,05). Constatou-se que 26,8% das pacientes apresentavam antecedentes familiares de câncer de mama, em ambos os grupos. Entre as ex-usuárias de TH, 43,3% foram submetidas a mamografias prévias, ao passo que entre as não usuárias, apenas 11,3% (p<0,001). O diâmetro médio do tumor foi menor entre as ex-usuárias de TH (2,3±1,1 cm), com predomínio de quadrantectomias (60%), quando comparadas as não usuárias (3,3±1,5 cm e 32%, respectivamente) (p<0,001). No estudo imuno-histoquímico, observou-se correlação positiva entre a presença de receptores de estrogênio e progesterona positivos e o uso de TH (p<0,001). Não houve correlação entre TH e c-erbB-2 e p53. CONCLUSÃO: nesta casuística, as mulheres na pós-menopausa que usaram TH prévia ao diagnóstico de câncer de mama apresentaram indicadores de prognóstico mais favoráveis quando comparadas às não usuárias.

Carcinoid tumour of male breast diagnosed by fine needle aspiration.

A primary carcinoid tumour of the breast in a 66-year-old man was diagnosed by fine-needle aspiration cytology. The nature of the lesion was proved by histochemical and immunocytochemical studies. The importance of a conclusive diagnosis is discussed and the value of immunocytochemical analysis as an aid to cytomorphologic diagnosis is demonstrated.

Detection of estrogen receptor in formalin-fixed and paraffin-embedded breast carcinoma: correlation with histological patterns.

The authors studied the expression of estrogen receptor (ER) in tissues of breast carcinomas which were previously fixed in formalin and paraffin-embedded. The ER expression was correlated with several histological findings, namely grade of differentiation, tumor necrosis, desmoplasia, lymphocytic infiltration and elastosis. The ER was detected in tissues using the avidin-biotin immunoperoxidase technique associated with the H222 monoclonal antibody from Abbott. All 39 biopsies were of infiltrating ductal carcinoma of breast and 16 of them expressed ER. The statistical analysis showed that the expression of ER was correlated with histological findings of good prognosis as well differentiated carcinomas, no tumor necrosis, absence or mild lymphocytic infiltration around the tumor cells and severe elastosis.

Considerações sobre o câncer localmente avançado de mama (CLAM) acrescidas de identificação dos receptores de estrogênios usando anticorpos monoclonais.

The effects of therapy in locally advanced breast cancer submitted to combined conventional telecobalt therapy plus chemotherapy with cyclophosphamide and 5-fluorouracil were studied in 49 patients. Associated to radical mastectomy in operable cases. Local tumor control was achieved in 86.7%. There were no local recurrences in those submitted to surgery but they reached 21.7% in inoperable patients who received only radiation therapy and chemotherapy. The median follow-up time for dead patients was 29.5 months and for living patients 79.3 months. The index of complete responses was 24.5% and the median disease free interval was 22.9 months. The overall survival rate, between three and five years, was 32.7%. Estrogen receptors were identified by using immunohistochemical assay ER-ICA and monoclonal antibody H222-SP gamma, Abbott. There were no differences in the complete response index, disease free interval and survival rates, among ER-positive and ER-negative patients, explained by the far advanced stage of the disease. ER-positivity was significantly correlated with histological features of the tumors: cell differentiation, presence of elastosis, absence of lymphocytic infiltration and absence of tumor necrosis.

Simple mucin-type carbohydrate antigens (T, sialosyl T, Tn and sialosyl-Tn) in breast carcinogenesis

Immunohistochemical analysis of the expression of simple mucin-type carbohydrate antigens (Tn, sialyl-Tn and T) was performed in a series of 43 cases of intraductal hyperplasia without atypia, 9 cases of intraductal hyperplasia with atypia, 54 cases of ductal carcinoma in situ (DCIS) and 26 cases of invasive breast carcinoma. We also studied 36 cases of isolated breast normal epithelium, 20 cases of 'normal' breast epithelium adjacent to neoplasms and 14 cases of apocrine metaplasia. All antigens were detected in different frequencies in normal, hyperplastic, metaplastic and neoplastic breast epithelium. Tn and sialyl-Tn are expressed more frequently in malignant than in benign breast epithelium; while Tn expression increases from normal to invasive carcinomas, sialyl-Tn increases until DCIS and drops in invasive carcinomas, suggesting that either there is a failure of a proportion of DCIS to progress to invasive carcinoma or loss of expression of sialyl-Tn when some carcinomas become invasive. The high frequency of Tn and sialyl-Tn expression in breast intraductal proliferations probably reflects incomplete glycosylation in these lesions, which is a well-known tumour-associated phenomenon and supports the assumption that such lesions are putative precursors of breast cancer. T antigen was expressed in all groups studied, but its prevalence differed significantly between normal and neoplastic epithelium. The expression of these antigens in epithelium adjacent to carcinomas is similar to that found in isolated normal breast epithelium, whereas apocrine metaplasia has a pattern of simple mucin-type glycosylation that is specific and distinct from that of the normal breast epithelium, with a high frequency of marked expression of Tn and sialyl-Tn. The similarity of the pattern of expression of simple mucin-type antigens in metaplasia and malignant neoplasia reduces the usefulness of these markers from a diagnostic standpoint.

Cytogenetic evaluation of 20 primary breast carcinomas

Chromosome analysis was performed on samples from 20 Brazilian patients with breast cancer. All the samples were from untreated patients who presented the clinical symptoms for months or years before surgical intervention. Six cases showed axillary lymph node metastases. Clonal chromosome abnormalities were detected in all cases. The numerical alterations most frequently observed involved the loss of chromosomes X, 19, 20, and 22 followed by gain of chromosomes 9 and 8. Among the structural anomalies observed, there was preferential involvement of chromosomes 11, 6, 1, 7, 3, and 12, supporting previous reports that these chromosomes may harbour genes of importance in the development of breast tumors. Two cases with a family history of breast cancer had in common total or partial trisomy 1.

Correlation between carotenoid concentrations in serum and normal breast adipose tissue of women with benign breast tumor or breast cancer

To evaluate the relationship between carotenoid concentrations in serum and breast tissue, we measured serum carotenoid concentrations and endogenous carotenoid levels in breast adipose tissue of women with benign breast tumor (n = 46) or breast cancer (n = 44). Before extraction, serum was digested with lipase and cholesterol esterase, and breast adipose tissue was saponified. Serum and tissue carotenoids were extracted with ether/hexane and measured by using HPLC with a C30 column. Serum retinoic acid was extracted with chloroform/methanol and measured using HPLC with a C18 column. There were no significant differences in serum carotenoids [lutein, zeaxanthin, cryptoxanthin (both α- and β-), α-carotene, all-trans β-carotene, 13-cis β-carotene and lycopene], retinoids (retinol, all-trans and 13-cis retinoic acids), and α- and -γ- tocopherol concentrations between benign breast tumor patients and breast cancer patients. A substantial amount of 9-cis β- carotene was present in adipose tissue and was the only carotenoid that had a significantly lower level in benign breast tumor patients than in breast cancer patients. Correlations between carotenoid concentrations in serum and in breast adipose tissue were determined by combining the data of the two groups. Concentrations of the major serum carotenoids except cryptoxanthin showed significant correlations with breast adipose tissue carotenoid levels. When the concentrations of serum carotenoids were adjusted for serum triglycerides or LDL, correlations between serum carotenoid concentrations and breast adipose tissue carotenoid levels markedly increased, including that of cryptoxanthin (P <0.001). The strong correlation between serum carotenoid concentrations and endogenous breast adipose tissue carotenoid levels indicate that dietary intake influences adipose tissue carotenoid levels as well as serum concentrations, and that adipose tissue is a dynamic reservoir of fat-soluble nutrients.

Tamoxifen down-regulates CaMKII messenger RNA levels in normal human breast tissue

Tamoxifen was proven to reduce the incidence of breast cancer by 49% in women at increased risk of the disease in the Breast Cancer Prevention Trial. In order to identify potential candidates to explain the preventive effect induced by tamoxifen on breast cancer, normal breast tissue obtained from 42 fibroadenoma patients, randomly assigned to receive placebo or tamoxifen, was analyzed by the reverse Northern blot and RT-PCR techniques. The cDNA fragments used on Northern blot membranes were generated by the Human Cancer Genome Project funded by the Ludwig Institute for Cancer Research and FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo, Brazil). Total RNA was obtained from normal breast tissue from patients with clinical, cytological and ultrasound diagnosis of fibroadenoma. After a 50-day treatment with tamoxifen (10 or 20 mg/day) or placebo, normal breast tissue adjacent to the tumor was collected during lumpectomy with local anesthesia. One differentially expressed gene, Calcium/calmodulin-dependent protein kinase II (CaMKII), was found to be down-regulated during TAM treatment. CaMKII is an ubiquitous serine/threonine protein kinase that has been implicated in the diverse effects of hormones utilizing Ca2+ as a second messenger as well as in c-fos activation. These results indicate that the down-regulation of CaMKII induced by TAM might represent alternative or additional mechanisms of the action of this drug on cell cycle control and response to hormones in normal human breast tissue.