Review of Polymorphism of the Calcium-Sensing Receptor Gene and Breast Cancer Risk.

Polymorphism of the calcium-sensing receptor gene (CaSR or CaR) has been associated with an increased risk for breast cancer. This receptor plays an important role in calcium homeostasis, and has also been detected in several tissues that are unrelated to calcium metabolism, such as the skin, brain, and breast. The calcium-sensing receptor on cellular level, it regulates cell differentiation, proliferation, cell death, and gene expression. In breast cancer cells, CaSR seems to stimulate secretion of the parathyroid hormone-related protein (PTHrP), which stimulates cellular proliferation. Likewise, some studies have supported not only an association between calcium receptor gene polymorphism and breast cancer risk, but also a higher aggressiveness and unfavorable outcomes in breast cancer, which led us to make a survey in Pubmed on the subject in the last 10 years. Thus, in the literature there is a paucity of studies on the subject and the aim of this review was to show the role of calcium-sensing receptor and its association with breast cancer risk.

Human Epidermal Growth Factor Receptor-2 gene polymorphism and breast cancer risk in women from the Northeastern region of Brazil.

OBJECTIVES: In the Human Epidermal Growth Factor Receptor-2 (HER2) rs1136201 variant, the presence of the G allele may promote cellular alterations and increase breast cancer risk, in addition to enhanced cellular proliferation, tumor aggressiveness, and metastases. The aim of this study was to investigate the presence of the single-nucleotide polymorphism (SNP) variant, rs1136201, within the HER2 gene in women from the Northeastern region of Brazil and breast cancer risk. METHODS: The study included 140 women who were divided into two groups, case (breast cancer) and control (without breast cancer), with 70 women in each group. Peripheral blood of each woman was drawn for the study of genomic Deoxyribonucleic acid (DNA) extracted from leukocytes using the genotyping technique by real-time polymerase chain reaction. RESULTS: The GG genotype occurred in 1 woman in both groups (1.4%) (p=0.32), while the AG genotype occurred in 19 (27.2%) and 13 (18.6%) women in the case and control (p=1.00) groups, respectively. No statistically significant difference in GG and AG genotypes was observed between the case and control groups in premenopausal women (p=1.00). Furthermore, no significant difference in genotypes was observed between the groups, among postmenopausal women (p=0.14). CONCLUSION: In this study, the HER2 rs1136201 polymorphism did not show any statistically significant association with breast cancer, both in premenopausal and postmenopausal women. Nevertheless, further studies with a larger sample size should be performed to assess the association of HER2 polymorphism with breast cancer risk in women from the Northeastern region of Brazil.

Assessment of IGF-1 expression in the peripheral blood of women with recurrent breast cancer.

Breast cancer is the most common malignancy affecting women worldwide. The insulin-like growth factor 1 (IGF-1) gene encodes a protein responsible for a wide variety of physiological processes, including differentiation and cell proliferation. Despite several studies on tumor tissues, no study has evaluated IGF-1 expression in the peripheral blood of women with recurrent breast cancer.In this cross-sectional study, IGF-1 expression in the peripheral blood of 146 women with breast cancer treated approximately 5 years ago was quantified by quantitative reverse transcription polymerase chain. The women were divided into 2 groups: non-recurrence (n = 85) and recurrence (n = 61). Statistical analysis of the data was performed using ANOVA, Mann-Whitney, and Chi-squared tests (P < .05).The results showed no significant difference in IGF-1 expression between the non-recurrence and recurrence groups (P = .988). In the subgroups of patients with lymph node involvement, no statistically significant difference was observed in IGF-1 expression between women with recurrence and those non-recurrence (P = .113). In patients without lymph node metastases, IGF-1 messenger ribonucleic acid (mRNA) expression levels were significantly higher in the non-recurrence group than in the recurrence group (P = .019). Furthermore, using the median IGF-1 mRNA expression as the cutoff point, it was obtained a statistically significant difference in tumor histological grade among women with recurrent breast cancer (P = .042).These data showed significantly higher IGF-1 expression in women without lymph node metastases in the non-recurrence group compared with the recurrence group. In addition, a significant difference was observed in median IGF-1 mRNA expression in relation to tumor histological grade in women with recurrent breast cancer.

A case-control study of Metallothionein-1 expression in breast cancer and breast fibroadenoma.

The overexpression of Metallothionein-1 (MT-1) may play an important role in breast cancer; however, few studies have compared MT-1 expression between breast cancer and fibroadenoma. A cross-sectional controlled study was performed in 66 premenopausal women, aged 20-49 years, who had been histologically diagnosed with breast fibroadenoma or breast cancer. The patients were divided into two groups: group A, control (fibroadenoma, n = 36) and group B, study (breast cancer, n = 30). Immunohistochemistry was performed on tissue samples of fibroadenoma and breast cancer patients to evaluate the expression of metallothionein using an anti-MT-1 polyclonal antibody (rabbit polyclonal anti-metallothionein-Catalog Number biorbyt-orb11042) at a dilution of 1:100. The data were analyzed using NOVA (p < 0.05). Microscopic analysis showed a higher concentration of anti-MT-1-stained nuclei in breast cancer tissues than in fibroadenoma tissues. The mean proportion of cells with anti-MT-1-stained nuclei was 26.93% and 9.10%, respectively, in the study and control groups (p < 0.001). Histological grade 3 tumors showed a significantly higher MT-1 expression than hitological grade 1 (p < 0.05), while breast tumors negative for estrogen-, progesterone- and HER2- receptors had a significantly higher MT-1 expression than positive breast tumors positive for these parameters (p < 0.05). MT-1 protein in women of reproductive age was significantly higher in breast cancer than in fibroadenoma in this study. Furthermore, there was higher MT-1 immunoreactivity in more aggressive tumors.

Expression of matrix metalloproteinase 2 and 9 in breast cancer and breast fibroadenoma: a randomized, double-blind study.

BACKGROUND: Matrix metalloproteinases (MMPs) 2 and 9 may play an important role in cell proliferation and dissemination of cancer. However, few studies have compared the expression of these proteins between breast cancer and fibroadenoma. MATERIAL AND METHODS: A randomized, double-blind study was carried out in 66 premenopausal women, aged 20-49 years, who had been diagnosed with fibroadenoma or breast cancer. The patients were divided into two groups: Group A, control (fibroadenoma, n=36) and Group B, study (cancer, n=30). Immunohistochemical analysis was performed using tissue samples of fibroadenoma and breast cancer to assess MMP-2 and MMP-9 antigen expression. Cells were considered positive if exhibiting brown cytoplasmic staining. Fisher's exact test was used to compare the percentage of cases with cells expressing MMP-2 and MMP-9 in control and study groups (p < 0.05). RESULTS: Light microscopy showed a higher concentration of cells with positive cytoplasmic staining for MMP-2 and MMP-9 expression in breast cancer than in fibroadenoma. The percentage of cases with cells expressing MMP-2 in the control and study groups was 41.67% and 86.11%, respectively (p < 0.0009), whereas the percentage of cases with cells expressing MMP-9 in groups A and B was 66.67% and 93.33%, respectively (p<0.0138). MMP-2 and MMP-9 positive expression was significantly higher in moderately differentiated tumors compared to well and poorly differentiated tumors, p <0.005 and p<0.001, respectively. CONCLUSIONS: The current study shows that MMP-2 and MMP-9 protein expression was significantly higher in the breast cancer than in the fibroadenoma and also in moderately differentiated breast cancer.

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.

Human Epidermal Growth Factor Receptor-2 gene polymorphism and breast cancer risk in women from the Northeastern region of Brazil

OBJECTIVES: In the Human Epidermal Growth Factor Receptor-2 (HER2) rs1136201 variant, the presence of the G allele may promote cellular alterations and increase breast cancer risk, in addition to enhanced cellular proliferation, tumor aggressiveness, and metastases. The aim of this study was to investigate the presence of the single-nucleotide polymorphism (SNP) variant, rs1136201, within the HER2 gene in women from the Northeastern region of Brazil and breast cancer risk. METHODS: The study included 140 women who were divided into two groups, case (breast cancer) and control (without breast cancer), with 70 women in each group. Peripheral blood of each woman was drawn for the study of genomic Deoxyribonucleic acid (DNA) extracted from leukocytes using the genotyping technique by real-time polymerase chain reaction. RESULTS: The GG genotype occurred in 1 woman in both groups (1.4%) (p=0.32), while the AG genotype occurred in 19 (27.2%) and 13 (18.6%) women in the case and control (p=1.00) groups, respectively. No statistically significant difference in GG and AG genotypes was observed between the case and control groups in premenopausal women (p=1.00). Furthermore, no significant difference in genotypes was observed between the groups, among postmenopausal women (p=0.14). CONCLUSION: In this study, the HER2 rs1136201 polymorphism did not show any statistically significant association with breast cancer, both in premenopausal and postmenopausal women. Nevertheless, further studies with a larger sample size should be performed to assess the association of HER2 polymorphism with breast cancer risk in women from the Northeastern region of Brazil.