Risk Of Developing Breast Cancer Research Articles

Diagnostic Potential Role of CXCL3 and Leptin Levels in Breast Cancer

     The risk of breast cancer development is believed to be attributed to the alterations of a number of key biological components. Within this context, elevated levels of some chemokines that act as growth factors and can promote cancer development. The current study was designed to evaluate CXCL3 (a chemokine C-X-C Motif Ligand 3) and leptin (a peptide hormone synthesized by adipose tissue with cytokine activity) serum of Iraqi breast cancer patients in comparison to healthy controls. A total of 90 participants consisted of 60 patients diagnosed with breast cancer and 30 healthy women as control group were enrolled into this case-control study. Venous blood samples were collected from all participants to evaluate CXCL3 and leptin serum levels using ELISA. The results demonstrated significantly (P≤0.001) higher mean levels of CXCL3 and leptin in breast cancer patients (1.19±0.10 ng/mL and 130.44± 3.72pg/mL) compared to those of their healthy counterparts (0.430± 0.02\ng/mL and 57.1± 3.2pg/mL respectively). Interestingly, vast majority of the assessed breast cancer cases (up to 95-98%) showed to have elevated serum levels of both of the assessed potential biomarkers (CXCL3 and leptin). The present study results suggest an association of both CXCL3 and leptin in breast cancer pathogenicity. This supports the possibility of utilizing these potential biomarkers for breast cancer early detection and diagnosis.

Exposure to outdoor ambient air toxics and risk of breast cancer: The multiethnic cohort

BackgroundA growing literature has reported associations between traffic-related air pollution and breast cancer, however there are fewer investigations into specific ambient agents and any putative risk of breast cancer development, particularly studies occurring in populations residing in higher pollution areas such as Los Angeles. ObjectivesTo estimate breast cancer risks related to ambient air toxics exposure at residential addresses. MethodsWe examined the relationships between ambient air toxics and breast cancer risk in the Multiethnic Cohort among 48,665 California female participants followed for cancer from 2003 through 2013. We obtained exposure data on chemicals acting as endocrine disruptors or mammary gland carcinogens from the National-Scale Air Toxics Assessment. Cox proportional hazards models were used to estimate breast cancer risk per one interquartile range (IQR) increase in air toxics exposure lagged by 5-years. Stratified analyses were conducted by race, ethnicity, and hormone receptor types. ResultsAmong all women, increased risks of invasive breast cancer were observed with toxicants related to industries [1,1,2,2-tetrachloroethane (hazard ratio [HR] = 4.22, 95% confidence interval [95% CI] 3.18–5.60), ethylene dichloride (HR = 2.81, 95% CI 2.20–3.59), and vinyl chloride (HR = 2.27, 95% CI 1.81, 2.85); these 3 agents were correlated (r2 = 0.45–0.77)]. Agents related to gasoline production or combustion were related to increased breast cancer risk [benzene (HR = 1.32, 95% CI 1.24, 1.41), ethylbenzene (HR = 1.20, 95% CI 1.13–1.28), toluene (HR = 1.29, 95% CI 1.20–1.38), naphthalene (HR = 1.11, 95% CI 1.02–2.22), acrolein (HR = 2.26, 95% CI 1.92, 2.65)]. Higher hazard ratios were observed in African Americans and Whites compared to other racial and ethnic groups (p-heterogeneity <0.05 for traffic-related air toxics, acrolein, and vinyl acetate). ConclusionsOur findings suggest that specific toxic air pollutants may be associated with increase breast cancer risk.

Upgrade Rates and Breast Cancer Development Among Germline Pathogenic Variant Carriers with High-Risk Breast Lesions.

High-risk lesions (HRL) of the breast are risk factors for future breast cancer development and may be associated with a concurrent underlying malignancy when identified on needle biopsy; however, there are few data evaluating HRLs in carriers of germline pathogenic variants (PVs) in breast cancer predisposition genes. We identified patients from two institutions with germline PVs in high- and moderate-penetrance breast cancer predisposition genes and an HRL in an intact breast, including atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), and lobular neoplasia (LN). We calculated upgrade rates at surgical excision and used Kaplan-Meier methods to characterize 3-year breast cancer risk in patients without upgrade. Of 117 lesions in 105 patients, 65 (55.6%) were ADH, 48 (41.0%) were LN, and 4 (3.4%) were FEA. Most PVs (83.8%) were in the BRCA1/2, CHEK2 and ATM genes. ADH and FEA were excised in most cases (87.1%), with upgrade rates of 11.8% (95% confidence interval [CI] 5.5-23.4%) and 0%, respectively. LN was selectively excised (53.8%); upgrade rate in the excision group was 4.8% (95% CI 0.8-22.7%), and with 20 months of median follow-up, no same-site cancers developed in the observation group. Among those not upgraded, the 3-year risk of breast cancer development was 13.1% (95% CI 6.3-26.3%), mostly estrogen receptor-positive (ER +) disease (89.5%). Upgrade rates for HRLs in patients with PVs in breast cancer predisposition genes appear similar to non-carriers. HRLs may be associated with increased short-term ER+ breast cancer risk in PV carriers, warranting strong consideration of surgical or chemoprevention therapies in this population.

Breast cancers in monoallelic MUTYH germline mutation carriers have clinicopathological features overlapping with those in BRCA1 germline mutation carriers.

Breast cancer patients referred to genetic counseling often undergo genetic testing with broad panels that include both breast cancer susceptibility genes as well as genes more specific for extramammary sites. As a result, patients are often incidentally found to have germline mutations in genes that are not necessarily related to breast cancer risk. One such gene is MUTYH. To understand the role MUTYH may play in breast cancer, the clinicopathological features of patients with monoallelic MUTYH germline mutation and breast cancer were examined. The clinicopathological characteristics of the breast cancers from patients with monoallelic MUTYH mutation were compared to breast cancer patients with other germline mutations in known breast cancer susceptibility genes, including ATM, BRCA1/2, CHEK2, and PALB2. The breast cancer patients who received genetic counseling but tested negative for the aforementioned gene mutations were used as a control group. Histologic characteristics of the breast cancers arising in monoallelic MUTYH mutation carriers had significantly larger tumor size, higher tumor grade, and more high-risk biomarker profiles (i.e., Her2-positive and triple-negative) than breast cancer patients with susceptibility genes, except for BRCA1. MUTYH mutation carriers also showed a trend of more frequent intratumoral divergency in terms of tumor grade and biomarker profiles. Although germline monoallelic MUTYH mutation is not thought to confer a meaningfully increased risk of breast cancer development, it may contribute to pathological aggressiveness and diversity of breast cancers when they sporadically arise in MUTYH carriers.

53 The Patient Demographic Details of Referrals for Risk Reducing Breast Surgery and Reconstruction to St Helen’s and Knowsley Teaching Hospitals Over a 5 Year Period

Abstract Background Breast cancer is the most common cause of cancer in women affecting 1 in 7 women in the UK. Hereditary breast cancers are present in up to 10% of all cases and are most commonly related to BRCA gene mutations. Bilateral risk reducing mastectomy (RRM) +/- reconstruction is the most effective strategy reducing breast cancer mortality risk. Reconstruction options can be classified into immediate vs delayed reconstruction and autologous vs alloplastic reconstruction. Complete reconstruction may take considerable time depending on waiting lists and may include additional aesthetic corrections such as lipomodelling and nipple reconstruction. Method Retrospective analysis of referrals (all ages) to a single surgeon at Whiston Hospital for breast reconstruction following RRM between 1/04/2015-1/04/2020. Results There were a total of 467 referrals. Of these, 76 (16%) were referred for breast reconstruction following RRM, 51 (67%) of these patients had confirmed genetic mutations and 24 (32%) had no genetic mutation. 48 (94%) patients were BRCA gene carriers of which 32 (63%) were BRCA2 carriers, 14 (27%) were BRCA1 carriers and 2 patients with unknown BRCA variants. There were 2 (4%) patients with CHEK2 mutations and 1 (2%) patient with Cowden’s syndrome. Conclusions There is currently no standardised guidance on the timing of RRM and reconstruction in high-risk patients. The risk of breast cancer in high-risk patients increases with age, and there is need for a risk stratification tool for RRM and reconstruction waiting lists, to identify patients with the highest risk of breast cancer development considering their personal and family history.

Obesity Associated with Prediabetes Increases the Risk of Breast Cancer Development and Progression-A Study on an Obese Rat Model with Impaired Glucose Tolerance.

Patients with comorbidities of obesity and diabetes are recognized to be at high risk of breast cancer development and face worse breast cancer outcomes. Though several reports showed the reinforced link between obesity, diabetes, and prediabetes with breast cancer, the underlying molecular mechanisms are still unknown. The present study aimed to investigate the underlying molecular link between increased risks of breast cancer due to coincident diabetes or obesity using a spontaneous obese rat model with impaired glucose tolerance (WNIN/GR-Ob rat). A single dose of solubilized DMBA suspension (40 mg/kg body weight) was orally administered to the animals at the age of 60 days to induce breast tumors. The tumor incidence, latency period, tumor frequency, and tumor volume were measured. Histology, immunohistochemistry, and immunoblotting were performed to evaluate the tumor morphology and expression levels of signal molecules. The development of mammary tumors in GR-Ob rats was characterized by early onset and shorter latency periods compared to control lean rats. While 62% of obese rats developed breast tumors, tumor development in lean rats was only 21%. Overexpression of ER, PR, Ki67, and p53 markers was observed in tumor tissues of obese rats in comparison with lean rats. The levels of the hallmarks of cell proliferation and angiogenesis involved in IGF-1/PI3K/Akt/GSK3β/β-catenin signaling pathway molecules were upregulated in obese rat breast tumors compared to lean rats. Furthermore, obesity with prediabetes is associated with changes in IGF-1 signaling and acts on PI3K/Akt/GSK3β/β-catenin signaling, which results in rapid cell proliferation and development of breast tumors in obese rats than the lean rats. These results indicate that tumor onset and development were faster in spontaneous obese rat models with impaired glucose tolerance than in their lean counterparts.

Breast Lesions of Uncertain Malignant Potential (B3) and the Risk of Breast Cancer Development: A Long-Term Follow-Up Study.

Breast lesions of uncertain malignant potential (B3) are frequently diagnosed in the era of breast cancer (BC) screening and their management is controversial. They are generally removed surgically, but some international organizations and guidelines for breast research suggest follow-up care alone or, more recently, propose vacuum-assisted excision (VAE). The risk of upgrade to BC is known, but very little data exist on its role as risk factor for future BC development. We analyzed 966 B3 lesions diagnosed at our institution, 731 of which had long-term follow-up available. Surgical removal was performed in 91%, VAE in 3.8%, and follow-up in 5.2% of cases. The B3 lesions included flat epithelial atypia (FEA), atypical ductal hyperplasia (ADH), lobular intraepithelial neoplasia (LIN), atypical papillary lesions (PLs), radial scars (RSs), and others. Overall, immediate upgrade to BC (invasive or in situ) was 22.7%. After long-term follow-up, 9.2% of the patients were diagnosed with BC in the same or contralateral breast. The highest risk was associated with ADH diagnosis, with 39.8% of patients upgraded and 13.6% with a future BC diagnosis (p < 0.0001). These data support the idea that B3 lesions should be removed and provide evidence to suggest annual screening mammography for women after a B3 diagnosis because their BC risk is considerably increased.

Vitamin D deficiency as a risk factor for breast cancer development.

10559 Background: Previous studies and meta-analyses have suggested that women with low levels of vitamin D may be at increased risk of breast cancer development and recurrence. The relationship is suspected to be inverse, nonlinear, and predominantly present in postmenopausal women. The purpose of this study was to use the TriNetX platform to determine the magnitude of breast cancer risk increase for women with significant vitamin D deficiency and evaluate the significance of menopause on vitamin D-associated breast cancer risk. Methods: The TriNetX platform was used to generate patient cohorts via International Classification of Disease-10 (ICD-10) codes. All patients were females over 40, had no prior history of breast cancer (C50), and had been diagnosed with menopause (Z78.0). One cohort had less than 20 ng/mL of vitamin D while the other had greater than 30 ng/mL. The cohorts were balanced for age, race, and ethnicity, resulting in 73,659 patients in each arm. They were then evaluated for the future development of breast cancer (C50). Two additional cohorts were created of premenopausal patients aged 40-55 using the same vitamin D parameters and cohort balancing. Results: Postmenopausal women with vitamin D levels below 20 ng/mL had a 45% greater risk of developing breast cancer (risk ratio 1.45, 95% CI (1.38,1.52), p-value &lt;0.0001). (Table) Deficient premenopausal women were also found to be at significantly increased risk although the absolute risk difference was small (relative risk 1.18, 95% CI (1.10,1.27), p-value &lt;0.0001). Conclusions: These results confirm and also quantify the previously-suspected increased breast cancer risk for women who are deficient in vitamin D. The impact of low vitamin D levels on breast cancer risk in premenopausal patients was statistically significant but small in magnitude, while postmenopausal women were found to have approximately 45% higher risk as compared to women who were not deficient. Vitamin D supplementation for all deficient postmenopausal women should be considered. [Table: see text]

Maternal Age at the Last Birth and the Risk for Breast Cancer: A Case Control-Retrospective Study and Mini-Review of the Literature

Objective: Maternal age at the last birth and the risk of developing breast cancer were subjects of epidemiologic research, with controversial results. In order to objectively assess the relationship between maternal age at the last birth and the risk of developing breast cancer, we carried out this case control-retrospective study. Material and Methods: In our case-control retrospective analysis, 342 women who visited two breast clinics in Greece and had given birth to live newborns were analyzed. Women with breast cancer were included in the case group, whereas women without the disease were included in the control group. All women underwent a clinical examination that included a breast ultrasound and, in those who were older than 40 years old, also a digital bilateral mammogram was performed. Results: Mann-Whitney test observed that p-value = 0.474 and concluded that there is no statistically significant difference in the distributions of maternal age at birth of the last child of the two groups of women and the risk of breast cancer development. Conclusion: Our study showed no statistically significant relationship between maternal age at the last birth and breast cancer. Further studies with a larger number of patients are mandatory in order to confirm this result.

Polymorphism of folate metabolism genes in breast cancer patients

Breast cancer is a widespread oncological disorder, which is considered one of the leading causes of mortality among women. DNA repair processes a well as its methylation involving genes of folate cycle play a crucial role in cancerogenesis. The aim of the study is to generalize the current data about association between polymorphic variants of folate cycle genes MTHFR С677Т (rs1801133), MTR A2756G (rs1805087), MTRR А66G (rs1801394) with risk of breast cancer development. The search of scientific papers has been conducted using PubMed and elibrary.ru sources. Original and randomized surveys published from 2008 till 2022 have been included in this review.&#x0D; The study has accumulated sufficient data on MTHFR С677Т polymorphic variant in breast cancer patients, having significant influence on disease development. However, the data about MTR A2756G and MTRR A66G variants is quite limited. According to the findigs of many scientific papers, there is no link between polymorphic variants of these genes and breast cancerogenesis manifestation. Such factors like ethniсity and sufficient consumption of folates with nutrition can have significant impact on results and conclusions of studies about role of folate cycle genes in breast cancer patients.&#x0D; Further investigation of MTHFR С677Т (rs1801133), MTR A2756G (rs1805087) and MTRR А66G (rs1801394) genetic polymorphic variants with consideration of gene-environment and gene-gene interactions could explain the presence of individual differences of breast cancer risk.

Effect of SMAD4 gene polymorphism on breast cancer risk in Bangladeshi women

BackgroundBreast cancer, one of the most prevalent cancer types among women worldwide as well as in Bangladesh, is the leading cause of cancer death in women throughout the globe. The risk of breast cancer development was found to be associated with genetic polymorphism according to several studies. As a convenient prognostic marker, a biomarker helps to identify disease progression, can lead to an effective therapeutic strategy, development of prognostic marker is very important for any cancer to initiate treatment strategy early to increase the possibility of the success rate of the treatment along with reduction of the treatment cost. This study aims to establish the correlation between polymorphism of SMAD4 rs10502913 and risk of breast cancer development in Bangladeshi women. This study was conducted on 70 breast cancer patients and 60 healthy volunteers through blood sample collection followed by DNA separation between the intervals of August 2019–October 2019. The collected DNA sample was arranged for the RFLP analysis of a PCR amplified fragments followed by gel electrophoresis. The obtained data was analyzed by structured multinomial logistic regression model.ResultsObtained different fragment size after gel electrophoresis indicated different genotypes in this experiment. Our findings demonstrated that mutant homozygous A/A genotype, plays a significant role in breast cancer development among Bangladeshi women (P = 0.006, OR = 4.9626, 95% CI = 1.9980–12.3261) compared to the reference homozygous G/G genotype. Moreover, heterozygous G/A genotype was also found to be significantly associated with the risk of breast cancer development (P = 0.0252, OR = 2.6574, CI = 1.1295–6.2525). Considering the A/A genotype and G/A genotype combined, it also indicates a strong association of breast cancer development in Bangladeshi women (P = 0.008, OR = 3.5630, CI = 1.6907–7.5068).ConclusionOur study indicated a novel association between SMAD4 (rs10502913) polymorphism and increased risk of breast cancer development in Bangladeshi women.

Study of Human Leukocyte Antigen-G gene 14-bp Ins/Del and Codon 93 (CAC/CAT) Polymorphisms Association with Breast Cancer Susceptibility

Human leukocyte antigen-G is a non-classic human leukocyte antigen I molecule. This protein is expressed aberrantly in numerous forms of malignant diseases like glioblastoma multiforme, ovarian cancer, lymphoblastic and breast cancer. Human leukocyte antigen-G polymorphisms association with breast cancer has been extensively studied. One amongst the foremost studied variants was human leukocyte antigen-G 14-base pair insertion/deletion polymorphism. Nevertheless, results are contradictory or inconclusive. We aim to investigate two human leukocyte antigen-G polymorphisms, 14-base pair insertion/deletion 3’ untranslated region and for the first time and codon 93 (CAC/CAT) polymorphisms potentially associated with breast cancer risk in the Tunisian population. This study involved 151 breast cancer patients and 187 healthy controls. Genotyping of the human leukocyte antigen-G codon 93 (CAC/CAT) and 14-base pair insertion/deletion variants was performed respectively by amplification-refractory mutation system and polymerase chain reaction. The analysis of genotype and allele frequencies revealed that human leukocyte antigen-G 14-base pair insertion/deletion polymorphism was associated with breast cancer susceptibility in the Tunisian population (Odds ratio=0.53, 95 % confidence interval=0.33-0.85, p=0.0022) without correlation with clinical parameters. We also observed an association of the human leukocyte antigen-G codon 93 (CAC/CAT) polymorphisms with breast cancer. In terms of analysis of the combined 14-base pair insertion/deletion and codon 93 CT genotype, we detected that the CC insertion/insertion and CC insertion/deletion genotype decrease the risk of breast cancer development (Odds ratio=0.2083; p=0.0097; Odds ratio=0.3571; p=0.0053, respectively). In addition, the haplotype frequency distribution analysis disclosed that the C insertion haplotype has a protective effect against breast cancer development (Odds ratio=0.4749; 95 % confidence interval=0.4425-0.9277; p=0.0153). Taken together, female’s homozygosity for human leukocyte antigen-G 14-base pair insertion and human leukocyte antigen-G codon 93 (CAC) alleles may protect against breast cancer susceptibility.

Practical recommendations for the treatment of patients with breast cancer (article 2)

Background. Breast cancer is one of the most widespread malignant diseases among women in the world. For the last few years, its rate has constituted about 20% of all tumor diseases in women. The annual standardized morbidity growth rate in Ukraine was 1,8% in the last decade. The cumulative risk of breast cancer development is 5,4% given that the life duration is 74 years. Treatment of patients with breast cancer. The treatment must be planned by several medical specialists including a surgical oncologist, a radiation therapist, a chemotherapist, and, if possible, a pathologist. This will allow local and systematic tumor therapy methods to be combined in the best way possible.&#x0D; Purpose – to systematize, generalize, and present the research data on modern approaches to diagnostic measures, movement of patients, and sequence of treatment approaches for locally advanced and metastatic breast cancer from the perspective of the Ukrainian healthcare system. Materials and methods. The article covers modern full-text publications, screening, and treatment protocols of patients with breast cancer, which were obtained from international and domestic sources and databases (e-catalog of Vernadsky National Library of Ukraine, Web of Science, Core Collection, Pubmed).&#x0D; Results. Місцево-поширений первинно-неоперабельний інвазивний рак грудної залози РГЗ, в тому числі інфільтративно-набрякова форма є первинно неоперабельними і вимагають призначення медикаментозної терапії на першому етапі лікування. Locally advanced primarily inoperable invasive breast cancer, including infiltrativeedematous form, is primarily inoperable and requires the prescription of drug therapy at the first stage of the treatment. Triple-negative and HER-2-dependent tumors also require presurgical drug therapy. Local treatment (surgery, radiation therapy) at the first stage is not indicated. The main goal of drug therapy in primarily inoperable forms of breast cancer is the reduction in the size of the tumor in order to achieve an operable condition. Presurgical drug therapy in primarily inoperable forms of breast cancer is carried out under the same rules as in primarily operable ones. Therapy of isolated local recurrences is aimed at full recovery and must be performed similarly to the treatment of primary tumor and involve necessary diagnostic and treatment methods (the diagrams are given in article 1). The treatment of advanced, disseminated breast cancer is palliative and intended to improve the quality of life and increase its duration. The main treatment method for metastatic disease is drug therapy. There is no single treatment standard for metastatic breast cancer. Selection of the drug therapy option is performed taking into account biological markers and clinical-anamnestic features of the patient. On the condition that individual approaches to the treatment of patients with breast cancer are used, the following improvements are quite possible: an increase in both recurrence-free and overall survival, a decrease in the number of complications and toxic manifestations, better compliance of the patients and improvement of their life quality. Systematization and individualization of treatment regimens, depending on the stage of the tumor process and biological features of the tumor, allow the practicing physician to plan and predict the types and the sequence of antitumor therapy.&#x0D; Conclusions. The deepening of our knowledge of breast cancer pathogenesis will contribute to the deeper implementation of individual approaches to the treatment of patients with this pathology. Continuous search will certainly lead to the appearance of new groups of drugs which may change the existing standards of treatment. The use of new pathogenetically relevant methods of biological, hormonal, and target therapy in the modern standards of treatment will allow both recurrence-free and overall survival of the patients to be increased.

High-Fat Diet as a Risk Factor for Breast Cancer: A Meta-Analysis.

High-fat diets have been identified as a major cause of obesity and a potential risk factor for breast cancer. Fat tissue, also known as adipose tissue, produces an excess of estrogen, which has been linked to an increased risk of breast cancer. Determining the impact of HFDs in the development and progression of breast cancer is essential, as it will enable us to identify the role of dietary modification in preventing and managing the disease. The impact of a high-fat diet (HFD) on the development of breast cancer in humans has yet to be fully explained, as very few human studies are available to effectively analyze the effect fatty food has on breast cancer development. This meta-analysis, therefore, seeks to determine thestrength of association, if any, between HFD and an increased risk of breast cancer development. This research will help inform good eating habits, potentially reducing the disease's incidence and outcome. This meta-analysis examined eight (8) papers from various nations examining the effect of a high-fat diet as a risk factor for breast cancer developmentbetween 2010 and 2020. The study employed the multivariable-adjusted hazard ratio (H.R.), odds ratio (OR), or relative risk (R.R.) from the studies. Breast cancer cases were histologically and radiologically confirmed in the studies evaluated, and validated food frequency questionnaires were used to assess their dietary patterns. This metanalysis study found a substantial link between a high-fat diet and an increased risk of breast cancer, with statistically significant results (I2 = 93.38%, p0.05). Changes in dietary fat consumption may thus help mitigate some of the unfavorable consequences of breast cancer and survival. Even if further research is needed to support this assertion, the findings are compelling enough to advocate for low-fat, healthy diets to avoid breast cancer.

The Role of Oral Fusobacterium nucleatum in Female Breast Cancer: A Systematic Review and Meta-Analysis.

Breast cancer is the world's most prevalent malignancy, with an increasing incidence and a predisposition for postpubertal females from all cultural and ethnic backgrounds. More recently, oral Fusobacterium nucleatum species have been observed in cancerous human breast tissue, drawing attention to the role of microbes in cancer pathogenesis. Investigating oral Fusobacterium nucleatum species as potential biomarkers for female-specific breast cancer. A systematic search in The Central Register of Controlled Trials, EMBASE, EBSCO, NCBI, and MEDLINE databases was undertaken from the 1st January, 1983-31st March, 2022. Articles included were in English and based on women between the ages of 18-96 years with confirmed gingivitis/periodontal disease and breast cancer diagnoses from registered specialists. Authors extracted data independently, and a meta-analysis of risk estimations measuring associations between oral Fusobacterium nucleatum species and female-specific breast cancer was elucidated via calculated relative risks and 95% confidence intervals. AXIS tool analysis revealed 78.70% of articles with a positive correlation between oral Fusobacterium nucleatum and female-specific breast cancer. The risk of breast cancer development increased with significant levels of oral Fusobacterium nucleatum due to gingivitis/periodontitis (relative risk = 1.78, 95% confidence interval = 1.63-1.91). Low-moderate statistical heterogeneity was found (I 2 = 41.39%; P = 0.02), and the importance of periodontal status on breast cancer pathogenesis was determined (relative risk = 1.24, 95% confidence interval = 1.01-1.30). Oral Fusobacterium nucleatum species are a risk factor for breast cancer development, thus elevating their biomarker potentiality.

The Effect of Aflatoxin B1 on Tumor-Related Genes and Phenotypic Characters of MCF7 and MCF10A Cells.

The fungal toxin aflatoxin B1 (AB1) and its reactive intermediate, aflatoxin B1-8, 9 epoxide, could cause liver cancer by inducing DNA adducts. AB1 exposure can induce changes in the expression of several cancer-related genes. In this study, the effect of AB1 exposure on breast cancer MCF7 and normal breast MCF10A cell lines at the phenotypic and epigenetic levels was investigated to evaluate its potential in increasing the risk of breast cancer development. We hypothesized that, even at low concentrations, AB1 can cause changes in the expression of important genes involved in four pathways, i.e., p53, cancer, cell cycle, and apoptosis. The transcriptomic levels of BRCA1, BRCA2, p53, HER1, HER2, cMyc, BCL2, MCL1, CCND1, WNT3A, MAPK1, MAPK3, DAPK1, Casp8, and Casp9 were determined in MCF7 and MCF10A cells. Our results illustrate that treating both cells with AB1 induced cytotoxicity and apoptosis with reduction in cell viability in a concentration-dependent manner. Additionally, AB1 reduced reactive oxygen species levels. Phenotypically, AB1 caused cell-cycle arrest at G1, hypertrophy, and increased cell migration rates. There were changes in the expression levels of several tumor-related genes, which are known to contribute to activating cancer pathways. The effects of AB1 on the phenotype and epigenetics of both MCF7 and MCF10A cells associated with cancer development observed in this study suggest that AB1 is a potential risk factor for developing breast cancer.

The Impact of Dietary Fat on Breast Cancer Incidence and Survival: A Systematic Review.

Breast cancer has become one of the most common cancers affecting women worldwide, and researchers have struggled to explore new avenues for managing it for decades. One of the ways was to analyze the diet and its importance concerning this disease. This review aims to study the effect dietary fat has on the risk of breast cancer incidence as well as its influence on the survival of breast cancer patients. The main population under consideration for this review is women older than the age of 18. A thorough and detailed search was conducted until July 21, 2022, using four databases: PubMed, ScienceDirect, Google Scholar, and The Cochrane Library. After screening, 22 articles were selected for inclusion in this review. Of the 22 articles, 12 were from PubMed, two from ScienceDirect, one from The Cochrane Library, and seven from Google Scholar. The risk of bias was assessed, and the required information was extracted from the articles. A systematic review of all the included articles found a significant correlation between dietary fat and an increased risk of breast cancer development and worsening the prognosis for patients already diagnosed with breast cancer. Although many overlapping factors may be responsible for this development, studies show a trend that suggests that this particular factor can be a contributor. Further studies need to be conducted to highlight the role of fat in the diet and the use of dietary modification to curb breast cancer rates.

Implicações éticas dos testes genéticos de suscetibilidade ao câncer de mama

Abstract Breast cancer is a public health problem because it is the malignant neoplasm with the highest incidence in women worldwide. The hereditary form corresponds to about 5% to 10% of all cases and is directly related to the inheritance of genetic mutations. The main ones occur in the BRCA1 and BRCA2 tumor suppressor genes. The identification of these mutations is extremely important because of the high risk of breast cancer development in this population, allowing differentiated screening strategies and the adoption of risk reduction measures. However, reflections on the ethical aspects related to the indiscriminate use of genetic testing are important and necessary. The objective of this study was to evaluate the knowledge and opinion of physicians of an oncology reference center on the indication of genetic tests for susceptibility to breast cancer given the ethical dilemmas to which they are submitted in medical practice.

PALB2 gene in breast cancer

Breast cancer represents the most commonly encountered form of malignant disease in women worldwide, which has been widely demonstrated to have a strong genetic predisposition. Therefore, it seems that most often it is inherited in an autosomal dominant manner, the most commonly encountered germline gene variant being represented by BRCA 1 and BRCA 2, followed by TP53, CDH1, PTEN and STK1. Recently PALB2 gene has been demonstrated to confer a moderate risk for breast cancer development. In this article the importance and the prevalence of the PALB2 gene is presented as well as the breast cancer risk is analyzed (based on various studies). To better manage and understand the risks we have detailed the newest monitoring and treatment options regarding a mutation in the PALB2 gene that leads to breast cancer.

Abstract 724: Examining the effects of obesity and weight loss on mammary tumor inflammation and fibrosis

Abstract Obesity significantly increases risk of breast cancer development, and following diagnosis, obese breast cancer patients have an overall worsened prognosis. The complex relationship of obesity to breast cancer growth and aggressiveness must continue to be examined. Within breast adipose tissue, obesity causes a state of chronic, macrophage-driven inflammation. Chronic inflammation is associated with increased extracellular matrix (ECM) deposition. Increased collagen within the mammary microenvironment is a risk factor for tumor formation, as well as more aggressive tumors, in mouse models. In breast tumors from obese patients, tumor desmoplasia is also found to be increased. To better understand how obesity affects mammary tumor growth, inflammation, and fibrosis, we used a diet-induced obesity mouse model paired with the estrogen receptor alpha (ERα)+ TC2 mammary tumor cell line in female FVB mice. We observed that TC2 mammary tumors grew significantly faster in obese mice compared to lean mice and had significantly more macrophage infiltration. TC2 tumors from obese mice also had significantly more collagen deposition than TC2 tumors from lean mice, indicating that obesity leads to more fibrotic tumors. To identify how weight loss alters the mammary gland and mammary tumor microenvironments, obese mice were switched from a high-fat diet to a low-fat diet for six weeks, to induce weight loss. In non-tumor-bearing mammary glands, weight loss led to a significantly decreased number of crown-like structures, a marker of adipose tissue inflammation, similar to observations in human adipose tissue. TC2 mammary tumors grew at an intermediate rate between tumors from lean and obese mice, indicating that weight loss may be a viable option to reduce tumor aggressiveness, particularly for obese patients with other breast cancer risk factors. Understanding these weight-related changes in the mammary gland and mammary tumor microenvironments will provide greater insight into possible interventions for obese breast cancer patients. Citation Format: Genevra M. Kuziel, Lisa M. Arendt. Examining the effects of obesity and weight loss on mammary tumor inflammation and fibrosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 724.