Protective Role In Breast Cancer Research Articles

Senescence-related genes as prognostic indicators in breast cancer survival.

Breast cancer is a leading cause of cancer-related mortality among women worldwide, particularly affecting those in their later years. As the incidence of breast cancer increases with age, understanding the biological mechanisms that link aging and cancer becomes crucial. Cellular senescence, a hallmark of aging, plays a dual role in cancer by inhibiting tumorigenesis while also contributing to tumor progression through the senescence-associated secretory phenotype (SASP). This study aims to investigate the prognostic significance of senescence-related genes in breast cancer. We utilized the SenMayo gene list, a comprehensive set of senescence-related genes, to analyze gene expression data from a large cohort of breast cancer samples. The data was sourced from the Kaplan-Meier plotter, an integrated database that compiles gene expression information from multiple independent cohorts. Cox proportional hazards regression and false discovery rate (FDR) corrections were employed to evaluate the correlation between gene expression and survival outcomes, aiming to establish a prognostic signature. Our findings demonstrate that higher expression levels of senescence-related genes are significantly associated with improved survival, while lower expression levels correlate with shorter survival outcomes. These results suggest that senescence-related pathways play a protective role in breast cancer, potentially serving as valuable prognostic indicators. The identification of a prognostic signature based on senescence-related genes underscores the importance of cellular senescence in breast cancer progression and survival. Our study highlights the potential of senescence-related biomarkers in enhancing patient stratification and informing treatment strategies, contributing to the growing body of literature on the intersection of aging and cancer.

The relation between obesity and breast cancer risk in women by considering menstruation status and geographical variations: a systematic review and meta-analysis

Given the increase in the incidence of breast cancer during the past decades, several studies have investigated the effects of variables on breast cancer, especially obesity. This systematic review and meta-analysis aims to evaluate any effects of obesity on breast cancer risk in women, before and after menopause, and in different continents.All forms of relevant literature examining any association between obesity and breast cancer, including cohort, case–control, and cross-sectional studies, were identified in the PubMed, Scopus, EMBASE, and Web of Science databases from January 1, 1990 until January 13, 2023. Body mass index (BMI) > 30 was used to indicate obesity. Every type of breast cancer was examined as outcome factors. The quality of the papers was evaluated using the Newcastle–Ottawa scale checklist. The Egger and Begg test was used to evaluate publication bias. To assess any extra impact of each research on the final measurement, a sensitivity analysis was carried out.One hundred and two studies were included in this meta-analysis. Respectively, 48 and 67 studies reported associations between obesity and breast cancer in pre and post menopausal women. Combining all studies, the pooled OR of the association between obesity and breast cancer in pre-menopausal women was OR = 0.93 CI: (0.85–1.1), (I2 = 65.4%), and for post-menopausal woman, OR = 1.26 CI: (1.19–1.34), (I2 = 90.5%).Obesity has a protective role in breast cancer among pre-menopausal women, but this relationship is statistically significant only in European women. The chance of developing breast cancer increases in post-menopausal women who are obese. This relationship is significant among Asian, North American, African and European women.

OBHS impairs the viability of breast cancer via decreasing ERα and Atg13

Breast cancer (BRCA) is one of the most threatening cancer types, especially among the female population. 70% of breast cancer are estrogen receptor α (ERα) positive and endocrine therapy is effective to decrease breast cancer risk. Autophagy, a highly conserved cellular recycling process, has been regarded to serve a protective role in BRCA. Autophagy-related gene 13 (Atg13) is participated in autophagy and is critical to autophagy initiation. Briefly, we observed that ERα, a well-known transcription factor that can promote breast cancer cell proliferation, expressed higher in breast cancer tissues. Moreover, ERα had a significant positive correlation with Atg13 and may be able to regulate the transcription of Atg13 via binding the promoter region of Atg13. Surprisingly, Oxabicycloheptene sulfonate (OBHS), the drug that we reported as a selective estrogen receptor modulator (SERM) before, may have the ability to decrease the expression of ERα and suppress the autophagy. In conclusion. We found that ERα could be involved in autophagy by binding the promoter of Atg13, and compound OBHS may be able to affect the viability of breast cancer cells by decreasing the expression of ERα and Atg13.

MiR-223-3p targeting epithelial cell transforming sequence 2 oncogene inhibits the activity, apoptosis, invasion and migration of MDA-MB-468 breast cancer cells.

PurposeThis research was to investigate the role of miR-223-3p targeting epithelial cell transforming sequence 2 oncogene (ECT2) in activity, apoptosis, invasion and migration of MDA-MB-468 breast cancer (BC) cells.MethodsThe human BC cell lines MDA-MB-468 were used for the experiment. They were divided into six groups: blank group (no plasmid transfection), NC group (negative control, transfected empty plasmid), miR-223-3p mimic group (transfected miR-223-3p mimic plasmid), miR-223-3p inhibitor group (transfected miR-223-3p inhibitor plasmid), si-ECT2 group (transfected si ECT2 plasmid) and miR-223-3p mimic+oe-ECT2 group (transfected with miR-223-3p mimic plasmid and ECT2 plasmid).ResultsCompared with the NC group, the mRNA and protein expression of Bax in miR-223-3p mimic and si-ECT2 groups were significantly increased, while the mRNA and protein expression of ECT2, Bcl-2, vascular endothelial growth factor (VEGF), and TGF-β1 were significantly decreased (all P<0.05). Compared with the NC group, the expression of miR-223-3p and the mRNA and protein expression of Bax were significantly decreased in the miR-223-3p inhibitor group, while the mRNA and protein expression of ECT2, Bcl-2, VEGF and TGF-β1 were significantly increased (both P<0.05). Compared with the single processing group, the mRNA and protein expression of Bax in the miR-223-3p mimic+si-ECT2 group were significantly increased, while the mRNA and protein expression of ECT2, Bcl-2, VEGF, and TGF-β1 were significantly decreased (all P<0.05).ConclusionMiR-223-3p targets and inhibits the expression of ECT2, thus inhibiting the invasion and migration of BC cells, and promoting cell apoptosis. miR-223-3p plays a protective role in BC.

Aspirin Treatment Effect and Association with PIK3CA Mutation in Breast Cancer: A Biomarker Analysis

BackgroundStudies suggest regular aspirin use decreases breast cancer (BRCA) risk, with high doses exerting an “anti-cancer” effect. Despite reports suggesting aspirin’s protective role in BRCA, no findings on aspirin dose association(s) with treatment outcomes have been reported, nor have any molecular subtype associations by which aspirin influences outcomes been elucidated. To interrogate aspirin’s effect and determine which populations may benefit from its use, we retrospectively explored data from 1227 patients with BRCA. In this population, 32 used high-dose aspirin (325 mg), 121 used low-dose aspirin (81 mg), and 1074 used no aspirin before and/or after diagnosis. Patients and MethodsSeveral association tests were performed to examine the correlations of clinical variables and PIK3CA mutations from 45 patients with BRCA who used 81 mg of aspirin daily. Kaplan-Meyer survival curves and the log-rank test were utilized to compare survival outcome differences for aspirin dose, usage history, and PIK3CA mutation status. Cox proportional hazards models were used to compute the multivariate hazard ratio (HR) for death. ResultsPatients who regularly used high-dose aspirin (325 mg) had better survival outcomes than those who used low-dose aspirin (81 mg) (HR, 0.094; 95% confidence interval [CI], 0.014-0.62; P = .014). Patients who used aspirin post-diagnosis only achieved significant benefits in overall survival (HR, 0.082; 95% CI, 0.023-0.3; P = 1.39E-04). Also, a subgroup of patients in the low-dose, long-term aspirin group with a PIK3CA mutation showed a small beneficial effect (HR, 0.37; 95% CI, 0.04-3.25; P = .37). ConclusionHigh-dose aspirin after diagnosis may confer BRCA treatment benefits. Future studies should assess the comprehensive mechanism of aspirin for the PIK3CA mutant subgroup in a large study.

Cyclooxygenase-2 immunoexpression in breast cancer: Progesterone receptor influence

BackgroundIn breast cancer cyclooxygenase-2 overexpression is related with poor outcomes, but the clinical relevance of cyclooxygenase-2 is still unclear. Progesterone receptor is a regulator of cyclooxygenase-2 expression. We postulate that progesterone receptor was associated to cyclooxygenase-2 expression and clinicopathologic factors in breast cancer. MethodsCyclooxygenase-2 and progesterone receptor expression was analyzed, by immunohistochemistry, in 31 cases of invasive ductal carcinoma. ResultsThe expression of cyclooxygenase-2 and progesterone receptor was observed in 64.5% and 45.2% of the tumors, respectively. We found 11 tumors with both cyclooxygenase-2 and progesterone receptor overexpression and they are related with tumor lower size and lower axillary node metastasis. ConclusionThese results suggest that progesterone receptor has a protective role in breast cancer by inhibiting chronic inflammatory pathway.

Breast Cyst Fluid Plasmin Activity and Its Effect on TGF-β2 Activation

There are two types of breast cyst and women with apocrine breast cyst may have a higher risk of developing breast cancer than cyst lined by flattened epithelium. Transforming growth factor-beta's growth inhibitory effect on epithelial cells suggests a potential protective role in breast cancer. The aim of this study was to investigate the presence of plasmin in both breast cyst groups and the possible role of plasmin on transforming growth factor beta activation. Presence of high plasmin level may indicate its importance on activation process, but some other proteases may also involve in this activation mechanism.

Fog2 excision in mice leads to premature mammary gland involution and reduced Esr1 gene expression

The critical role for GATA family proteins in maintaining the normal (non-transformed) cell state is corroborated by the recent findings of mutations or methylation in GATA genes both in primary cancers and tumor lines including breast. Previously, microarray profiling studies determined that the highest expression of both GATA3 and ESR1 (estrogen receptor alpha) is seen in tumors associated with the most favorable survival outcomes, whereas the lowest expression of GATA3 is detected in tumor subtypes showing the worst outcomes. At this time, genes and pathways that are regulated by GATA3 in the mammary gland are not well defined. We have previously established a requirement for FOG (Friend Of GATA) cofactors during mouse development. Here we report that in the murine mammary gland Fog2 gene expression is upregulated upon pregnancy and lactation with prominent expression in the epithelial cells of the gland during post-lactational regression. Mammary-specific deletion of Fog2 identified a role for this gene during gland involution; excision of the Fog2 gene leads to the accelerated involution of the gland despite diminished levels of the remodeling enzymes. Importantly, the levels of several genes linked to the control of cancerous transformation in the breast (Esr1, Prg and Foxa1) are significantly reduced upon Fog2 excision. This implicates FOG2 in the maintenance of epithelial cell differentiation in the mammary gland and in performing a protective role in breast cancer.

Role of single nucleotide polymorphisms and haplotypes in BRCA1 in breast cancer: Czech case–control study

We aimed at determining whether any association exists between six single nucleotide polymorphisms in breast cancer associated gene (BRCA1) and the risk of breast cancer. We constructed haplotypes and analyzed their importance as well. Clinico-pathological characteristics of breast cancer patients were included in the study to evaluate the prognostic impact of BRCA1 polymorphisms and haplotypes. Polymerase chain reaction-restriction fragment length polymorphism-based genotyping assays were used to determine the frequency of polymorphisms in codons 356, 871, 1038, 1183, 1436, and 1613 of BRCA1 in a group of 306 incident breast cancer patients and 313 unaffected controls of Czech origin. Statistical analyses revealed that the BRCA1 Arg356 allele may play a protective role in breast cancer (age-adjusted OR = 0.61, CI = 0.39-0.94, p = 0.026). We also observed a significant correlation between polymorphism Gln356Arg and stage (p = 0.026) in premenopausal cases suggesting that carriers of the wild Gln356Gln allele are at significantly higher risk of advanced disease. The most common haplotypes of BRCA1 did not play a significant role in breast cancer either as risk factors or as prognostic factors. The study on rare BRCA1 haplotypes however should be repeated using larger groups. In conclusion, the BRCA1-Gln356 allele presents risk factor in the onset and progression of breast cancer in Czech population and its use as a possible screening tool should be considered.

Physical activity and breast cancer risk among Asian-American women in Los Angeles: a case-control study.

To the authors' knowledge, there have been few studies published to date regarding physical activity patterns and breast cancer risk in Asian and Asian-American women. The authors conducted a population-based case-control study of 501 Asian-American women with incident breast cancer and a control group of 594 Asian-American women in Los Angeles County to evaluate the role of lifetime physical activity on breast cancer risk. Information concerning lifetime recreational physical activity (i.e., type of activity, duration [years], and frequency [average hours per week]) and occupational physical activity was obtained using a structured questionnaire that was administered in person. Increasing years and levels (average metabolic equivalent [MET] hours per week) of lifetime recreational activity were associated with a significantly reduced risk of breast cancer after adjusting for demographic factors, migration history, and menstrual and reproductive factors. Compared with women who had no lifetime recreational physical activity, <or= 3 MET hours per week, > 3-6 MET hours per week, > 6-12 MET hours per week, and > 12 MET hours per week of activity were associated with significantly reduced risk, with odds ratios (and 95% confidence intervals) of 0.91 (0.55-1.49), 0.65 (0.39-1.10), 0.53 (0.31-0.90), and 0.47 (0.28-0.80), respectively (P value for trend < 0.001). The risk of breast cancer was associated inversely with occupational physical activity, although the result was not statistically significant. The findings of the current study provide further support for the finding that physical activity has a protective role in breast cancer.

Role of steroid hormones and growth factors in breast cancer.

Breast cancer is the most common cancer in women worldwide and its incidence is increasing. Oestrogens and mitogenic growth factors may play an important role in the development of breast cancer, whereas inhibitory growth factors may prevent the development of breast cancer. Only about 5 to 10% of cases of breast cancer are due to inheritance of mutations in the BRCA1 or BRCA2 tumour suppressor genes. Mutations in the p53 tumour suppressor gene are commonly found in sporadic breast cancers. Retinoic acid and carotenoids may play a protective role in breast cancer since they inhibit the growth of the oestrogen receptor-positive MCF-7 breast cancer cell line. The presence of oestrogen and progesterone receptors predicts the likelihood of benefit from hormonal therapy. Amplification of the c-erbB2 oncogene in breast cancers is associated with a poor prognosis. It is now apparent that there is a complex, productive cross-talk between oestrogen-directed and growth factor-directed pathways which are believed to markedly reinforce their individual cellular effects on growth and gene responses.

Immunology and immunotherapy of human breast cancer

The question of whether host immune factors play a protective role in breast cancer has been long debated. Early evidence based predominantly on histopathologic changes seen in ipsolateral axillary lymph nodes was suggestive. More recently, the availability of quantitative in vivo and in vitro tests of cellular and humoral immunity in breast cancer has given further support to this concept. A number of attempts have utilized both active and passive techniques of immunotherapy, with or without cytoreductive chemotherapy, to combat the disease. This review summarizes the literature pertaining to immunology and immunotherapy of breast cancer with the hope that such knowledge may lead to further improvements in our skill in the treatment of human breast cancer.