Ki-67 antigen expression in the mammary epithelium of female rats in persistent estrus treated with anastrozole.

OBJECTIVES: To evaluate Ki-67 antigen expression in mammary epithelium of female rats in persistent estrus treated with anastrozole. MATERIALS AND METHODS: Twenty-eight Wistar-Hanover female rats in persistent estrus induced by subcutaneous injection of 1.25 mg of testosterone propionate in the second day of life were randomly divided into two groups, control and experimental, with 14 animals each. The animals of control group received only the vehicle (propyleneglycol) and the animals of group experimental received 0.125 mg daily of anastrozole by gavage during 28 days. After 28 days of treatment, all animals were sacrificed and the first pair of abdominal-inguinal mammary glands was removed and fixed in 10% buffered formalin to investigate Ki-67 antigen expression by immunohistochemistry. RESULTS: The mean percentage of Ki-67-stained nuclei per 500 cells in the mammary epithelium was 76.97 ± 0.76 and 14.44 ± 2.02 [mean ± standard error of the mean (SEM)] in the control and experimental groups, respectively (p < 0.0001). CONCLUSIONS: Anastrozole treatment significantly reduced Ki-67 expression in the mammary epithelium of rats in persistent estrus.

Evaluation of Ki-67 antigen expression in the vaginal epithelium of castrated female rats treated with raloxifene and tamoxifen: a comparative study.

OBJECTIVE: The aim of this study was to evaluate the effects of raloxifene and tamoxifen on Ki-67 antigen expression in the vaginal epithelium of castrated rats. MATERIAL AND METHODS: Thirty-nine virgin, adult, castrated female Wistar-Hannover rats were randomly divided into three groups: Group I (control, n = 13), Group II (raloxifene, n = 13) and Group III (tamoxifen, n = 13). After confirmation of their hypoestrogenic state, the rats were given 0.5 ml of propylene glycol (vehicle), 750 µg of raloxifene or 250 µg of tamoxifen, respectively, by gavage, for 30 days. On the 31st day, the rats were euthanized and their vaginas removed and fixed in 10% buffered formalin for of Ki-67 immunohistochemical evaluation. Data were analyzed using Levene's test and Tukey's method (p < 0.05). RESULTS: Mean Ki-67 expression in groups I, II and III was 27 ± 2.6, 32.3 ± 1.9 and 43.7 ± 3.5, respectively. In Group III (tamoxifen), there was a greater proportion of stained cells compared to Groups I and II (p < 0.0003), with no statistically significant difference between Groups I and II (p = 0.3626). CONCLUSIONS: The present results show that tamoxifen significantly increased cell proliferation in the vaginal epithelium of the castrated rats and no difference between the raloxifene and control groups.

Evaluation of estrogen receptor expression in low-grade and high-grade astrocytomas.

OBJECTIVE: This study aims to compare estrogen receptor expression between low and high-grade astrocytomas. METHOD: A study using paraffin blocks of glial tumors from the Anatomy Pathology archives of São Marcos Hospital was carried out and began after approval by the Review Board of the Federal University of Piaui. Specimens were histochemically marked with an anti-ER alpha antibody. Brown-stained nuclei were considered positive, regardless of reaction intensity. Data were statistically analyzed using the Mann-Whitney test and Spearman's correlation. Statistical significance was established at p<0.05. RESULTS: The mean percentage of nuclei stained with anti-ER alpha in low-and high-grade astrocytomas was 0.04 and zero, respectively, while Spearman's correlation showed a strong negative association between low and high-grade tumors (p<0.001) and (r= -0.67), respectively. CONCLUSION: In the current study, estrogen receptor expression was positive only in low-grade astrocytomas and nil in high-grade astrocytomas, showing that ER expression declines with the grade of tumor malignancy.

A comparative study of Ki-67 antigen expression between luminal A and triple-negative subtypes of breast cancer.

Tumor biomarkers such as hormone receptors, HER-2 and Ki-67 are used routinely in clinical practice for classification of molecular subtypes of breast cancer. Cell proliferation evaluated by Ki-67 antigen expression is important to determine tumor aggressiveness. However, there is a paucity of studies comparing Ki-67 expression in an expressive number of cells among molecular subtypes of breast cancer, particularly among less and more aggressive tumors, such as luminal A and triple-negative, which have led us to the present study. The current study included invasive ductal carcinoma samples of 59 patients, which were divided into two groups: luminal A (n = 29) and triple-negative (n = 30). For immunohistochemical reaction, the samples were incubated with monoclonal anti-Ki-67 antibody (clone MIB1) and cells expressing Ki-67 protein were identified by dark brown staining of the nuclei, counting at least 600 cells per slide. The mean percentages of stained nuclei were analyzed by Student's t test (p < 0.05). The mean percentage of nuclei stained with anti-ki-67 was 10.14 and 77.22 in luminal A and triple-negative breast cancers, respectively (p < 0.0001). Our study showed a high cell proliferation of triple-negative breast cancer in comparison with luminal A, justifying its aggressiveness and poor clinical outcome.

Comparative study between ultrasound-guided fine needle aspiration cytology of axillary lymph nodes and sentinel lymph node histopathology in early-stage breast cancer.

The replacement of sentinel lymph node biopsy (SNB) by ultrasound-guided fine-needle aspiration (US-guided FNA) cytology of axillary lymph nodes is controversial, despite the simplicity and reduced cost of the latter. In the present study, US-guided FNA was performed in 27 patients with early-stage breast cancer for comparison with SNB. Data were analyzed by calculation of sample proportions. Tumor subtypes included invasive ductal carcinoma (85%), invasive lobular carcinoma (7%), and tubular and metaplastic carcinoma (4%). FNA had a sensitivity of 45%, specificity of 100%, positive predictive value of 100% and a negative predictive value of 73%. Axillary lymph node cytology obtained by US guided-FNA in patients with breast cancer had a specificity similar to that of sentinel lymph node histopathology in the presence of axillary node metastases. However, when lymph node cytology is negative, it does not exclude the existence of metastatic implants, due to its low sensitivity in comparison to sentinel lymph node histopathology.

Use of anastrozole in the chemoprevention and treatment of breast cancer: A literature review.

Aromatase inhibitors have emerged as an alternative endocrine therapy for the treatment of hormone sensitive breast cancer in postmenopausal women. The use of third-generation inhibitors represented by exemestane, letrozol and anastrozole is currently indicated. Anastrozole is a nonsteroidal compound and a potent selective inhibitor of the aromatase enzyme. Although a few studies have shown that its pharmacodynamic and pharmacokinetic properties may be affected by interindividual variability, this drug has been recently used in all configurations of breast cancer treatment. In metastatic disease, it is currently considered the first-line treatment for postmenopausal women with estrogen receptor-positive breast tumors. Anastrozole has shown promising results in the adjuvant treatment of early-stage breast cancer in postmenopausal women. It has also achieved interesting results in the chemoprevention of the disease. Therefore, due to the importance of anastrozole both for endocrine treatment and chemoprevention of hormone-sensitive breast cancer in postmenopausal women, we proposed the current literature review in the SciELO and PubMed database of articles published in the last 10 years.

Bcl-2 antigen expression in luminal A and triple-negative breast cancer.

Biomarkers for the prognosis of breast cancer have been routinely used in clinical practice, including the expression of hormone receptors, Ki-67 and HER-2. More recently, Bcl-2 has been recognized as an important prognostic factor in breast cancer, although controversies persist with respect to the significance of its expression. The aim of the present study was to evaluate Bcl-2 antigen expression in luminal A and triple-negative breast cancer. Sixty women with invasive ductal carcinoma were included in the study and divided into two groups: Group A (luminal A) and Group B (triple-negative), with 30 cases in each group. Immunohistochemistry was performed on tissue sections to evaluate Bcl-2 antigen expression. Fisher's exact test was used to compare the proportions of cases with cells expressing Bcl-2 between the two subtype cancer groups, with statistical significance being established at p < 0.05. The number of cases with cells expressing Bcl-2 in Groups A and B was 26 (86.7%) and 12 (40.0%), respectively (p < 0.0003). In the present study, the expression of the anti-apoptotic protein Bcl-2 was greater in luminal A breast cancer tissue samples compared to triple-negative breast cancer.

Large mammary hamartoma of axillary supernumerary breast tissue.

Hamartoma is an uncommon breast tumor and it is extremely rare to find it in ectopic breast tissue. We report the first case, to our knowledge, of a large hamartoma axillary supernumerary breast tissue. This report describes the case of a 33-year-old Brazilian patient who detected a lump in her left axillary supernumerary breast tissue at the same time as she was diagnosed with systemic erythematous lupus and corticoid treatment was initiated. The lesion showed progressive growth, reaching considerable proportions within a year, and it was removed with good esthetic and functional results.

Expression of estrogen and progesterone receptors in astrocytomas: a literature review.

Gliomas are the most common type of primary central nervous system neoplasm. Astrocytomas are the most prevalent type of glioma and these tumors may be influenced by sex steroid hormones. A literature review for the presence of estrogen and progesterone receptors in astrocytomas was conducted in the PubMed database using the following MeSH terms: "estrogen receptor beta" OR "estrogen receptor alpha" OR "estrogen receptor antagonists" OR "progesterone receptors" OR "astrocytoma" OR "glioma" OR "glioblastoma". Among the 111 articles identified, 13 studies met our inclusion criteria. The majority of reports showed the presence of estrogen and progesterone receptors in astrocytomas. Overall, higher tumor grades were associated with decreased estrogen receptor expression and increased progesterone receptor expression.

CYP2D6 gene polymorphisms in Brazilian patients with breast cancer treated with adjuvant tamoxifen and its association with disease recurrence.

At present, there is controversy regarding the efficacy of tamoxifen in breast cancer patients who are carriers of cytochrome P450 2D6 (CYP2D6) gene polymorphisms, in terms of recurrence and overall survival. Thus, the aim of the present study was to investigate the association of the CYP2D6 *4, *10 and *17 gene polymorphisms with breast cancer recurrence in a Brazilian population. The cohort comprised 40 receptor-positive breast cancer patients without recurrence and 40 with distant recurrence. A 3-ml sample of peripheral blood was collected from each patient to determine the presence of the *4, *10 and *17 single nucleotide polymorphisms of the CYP2D6 gene by quantitative polymerase chain reaction analysis. There was no statistically significant difference between the two groups regarding the polymorphism frequency (P=0.246). The results revealed that intermediate metabolizers occurred in 5% of patients without recurrence and in 15% of those with distant recurrence. Poor metabolizers occurred in only 1 patient (2.5%) per group, and there was no significant difference between the groups (P=0.789). The present study concluded that the CYP2D6 gene polymorphism in women with hormone-sensitive breast cancer treated with tamoxifen was not associated with disease recurrence.

Evaluation of estrogen receptor expression in low-grade and high-grade astrocytomas

SUMMARY OBJECTIVE: This study aims to compare estrogen receptor expression between low and high-grade astrocytomas. METHOD: A study using paraffin blocks of glial tumors from the Anatomy Pathology archives of São Marcos Hospital was carried out and began after approval by the Review Board of the Federal University of Piaui. Specimens were histochemically marked with an anti-ER alpha antibody. Brown-stained nuclei were considered positive, regardless of reaction intensity. Data were statistically analyzed using the Mann-Whitney test and Spearman's correlation. Statistical significance was established at p<0.05. RESULTS: The mean percentage of nuclei stained with anti-ER alpha in low-and high-grade astrocytomas was 0.04 and zero, respectively, while Spearman's correlation showed a strong negative association between low and high-grade tumors (p<0.001) and (r= −0.67), respectively. CONCLUSION: In the current study, estrogen receptor expression was positive only in low-grade astrocytomas and nil in high-grade astrocytomas, showing that ER expression declines with the grade of tumor malignancy.

RESUMO OBJETIVO: O objetivo deste estudo é comparar a expressão do receptor de estrogênio entre astrocitomas de baixo e alto grau. MÉTODO: Foi realizado um estudo usando blocos de parafina de tumores gliais dos arquivos de Anatomia Patológica do Hospital São Marcos e iniciado após aprovação pelo Comitê de Ética da Universidade Federal do Piauí. Os espécimes foram marcados histoquimicamente com anticorpo anti-ER alpha. Os núcleos corados em marrom foram considerados positivos, independentemente da intensidade da reação. Os dados foram analisados estatisticamente utilizando o teste de Mann-Whitney e a correlação de Spearman. A significância estatística foi estabelecida em p<0,05. RESULTADOS: A porcentagem média de núcleos corados com anti-ER alfa em astrocitomas de baixo e alto grau foi de 0,04 e zero, respectivamente, enquanto a correlação de Spearman mostrou uma forte correlação negativa entre tumores de baixa e alta qualidade (p<0,001) e (r=-0,67), respectivamente. CONCLUSÕES: No presente estudo, a expressão do receptor de estrogênio foi positiva apenas em astrocitomas de baixo grau e nula em astrocitomas de alto grau, mostrando que a expressão de ER diminui com o grau de malignidade tumoral.

Use of anastrozole in the chemoprevention and treatment of breast cancer: A literature review / Uso do anastrozol na quimioprevenção e no tratamento do câncer de mama: uma revisão da literatura

Summary Aromatase inhibitors have emerged as an alternative endocrine therapy for the treatment of hormone sensitive breast cancer in postmenopausal women. The use of third-generation inhibitors represented by exemestane, letrozol and anastrozole is currently indicated. Anastrozole is a nonsteroidal compound and a potent selective inhibitor of the aromatase enzyme. Although a few studies have shown that its pharmacodynamic and pharmacokinetic properties may be affected by interindividual variability, this drug has been recently used in all configurations of breast cancer treatment. In metastatic disease, it is currently considered the first-line treatment for postmenopausal women with estrogen receptor-positive breast tumors. Anastrozole has shown promising results in the adjuvant treatment of early-stage breast cancer in postmenopausal women. It has also achieved interesting results in the chemoprevention of the disease. Therefore, due to the importance of anastrozole both for endocrine treatment and chemoprevention of hormone-sensitive breast cancer in postmenopausal women, we proposed the current literature review in the SciELO and PubMed database of articles published in the last 10 years.

Resumo Os inibidores de aromatase têm emergido como uma endocrinoterapia alternativa para o tratamento de câncer de mama sensível a hormônios em mulheres pós-menopáusicas. A utilização de inibidores de terceira geração, representados por exemestano, letrozol e anastrozol, é atualmente indicada. Anastrozol é um composto não esteroide e um inibidor potente e seletivo da enzima aromatase. Embora alguns estudos tenham demonstrado que as suas propriedades farmacodinâmicas e farmacocinéticas podem ser afetadas pela variabilidade interindividual, esse fármaco tem sido recentemente utilizado em todas as configurações de tratamento do câncer de mama. Na doença metastática, é atualmente considerado o tratamento de primeira linha em mulheres pós-menopáusicas com tumores de mama e receptor de estrogênio positivo. O anastrozol tem mostrado resultados promissores no tratamento adjuvante do câncer de mama em estágio inicial em mulheres na pós-menopausa. Ele também conseguiu resultados interessantes na quimioprevenção da doença. Portanto, em virtude da importância do anastrozol tanto no tratamento endócrino quanto na quimioprevenção do câncer de mama hormoniossensível em mulheres na pós-menopausa, propusemos a atual revisão da literatura na base de dados SciELO e PubMed de artigos publicados nos últimos 10 anos.

Expression of estrogen and progesterone receptors in astrocytomas: a literature review

Gliomas are the most common type of primary central nervous system neoplasm. Astrocytomas are the most prevalent type of glioma and these tumors may be influenced by sex steroid hormones. A literature review for the presence of estrogen and progesterone receptors in astrocytomas was conducted in the PubMed database using the following MeSH terms: “estrogen receptor beta” OR “estrogen receptor alpha” OR “estrogen receptor antagonists” OR “progesterone receptors” OR “astrocytoma” OR “glioma” OR “glioblastoma”. Among the 111 articles identified, 13 studies met our inclusion criteria. The majority of reports showed the presence of estrogen and progesterone receptors in astrocytomas. Overall, higher tumor grades were associated with decreased estrogen receptor expression and increased progesterone receptor expression.

Quantification of angiogenesis induced in rabbit cornea by breast carcinoma of women treated with tamoxifen.

BACKGROUND: The aim of this study was to evaluate the effect of tamoxifen on angiogenesis induced in rabbit cornea by breast carcinoma from post-menopausal women. METHODS: Thirteen post-menopausal women with operable, estrogen receptor-positive breast carcinomas, treated with 20 mg of tamoxifen daily for 30 days prior to undergoing definitive surgery, participated in this study. Twenty-six virgin female New Zealand white rabbits, 3-4 months old, weighing approximately 2.5 kg each, were divided into two groups of 13 animals and received corneal implants of tumor either pre- or post-tamoxifen treatment. After 10 days, the animals were sacrificed, the region of the cornea between the tumor implant and the limbus was removed and quantification of angiogenesis was carried out by evaluating the entire hematoxylin-eosin stained slide, using a 10x objective lens (100x magnification). Student t-test was used in the statistical analysis of the data and statistical significance was established at P < 0.05. RESULTS: Mean microvessel count was 106.8 +/- 5.9 pre-tamoxifen treatment and 54 +/- 5.6 post-treatment. According to Student t-test, there was a significant reduction in mean microvessel density following treatment with tamoxifen (P < 0.001). CONCLUSIONS: Rabbit cornea proved to be an interesting experimental model for the quantification of angiogenesis. Tamoxifen, when administered for 30 days to post-menopausal women with breast cancer, significantly inhibited angiogenesis induced by tumor fragments in rabbit cornea.