Heba Mohammed Arafat

Background: Breast cancer outcomes improve substantially with earlier detection, yet mammography performance can be limited in dense breasts and may lead to false-positive investigations. Circulating microRNAs (miRNAs) and lipidomic/metabolomic signatures have emerged as promising minimally invasive biomarkers that could complement imaging for early-stage detection. The aim of this systematic review and meta-analysis is to evaluate the diagnostic accuracy of circulating microRNAs and lipidomic/metabolomic biomarkers for early breast cancer detection and to explore between-study heterogeneity. Materials and methods: A PRISMA 2020–compliant systematic review and meta-analysis were conducted. MEDLINE (PubMed), Web of Science, Scopus, Springer, ScienceDirect, and the Cochrane Library were searched for eligible diagnostic studies assessing circulating microRNAs and lipidomic/metabolomic biomarkers measured in serum or plasma. No language restrictions were applied. Non-English reports were screened and, when potentially eligible, translated for full-text assessment and data extraction. Studies using whole blood were excluded. Study quality was assessed using QUADAS-2. Random-effects models (DerSimonian–Laird) pooled sensitivity, specificity, likelihood ratios, diagnostic odds ratio (DOR), and summary ROC (SROC) area under the curve (AUC). Heterogeneity was evaluated using Q and I ² statistics, and small-study effects were assessed using Deeks’ test. Results: Thirty-two studies (2015–2025) comprising 6,935 participants (3,697 breast cancer cases; 3,238 controls) were included. Pooled sensitivity was 0.87 (95% CI [0.83, 0.90]) and pooled specificity was 0.84 (95% CI [0.79, 0.88]), with pooled DOR 46.10 (95% CI [27.80, 76.70]), PLR 5.17 (95% CI [3.99, 6.68]), NLR 0.16 (95% CI [0.13, 0.21]), and SROC AUC 0.92 (95% CI [0.87, 0.94]). Heterogeneity was substantial (I ² = 88.29% for sensitivity; I ² = 90.20% for specificity). In subgroup analyses, serum-based studies showed higher pooled specificity than plasma-based studies. A formal threshold effect assessment did not reveal a statistically significant correlation between sensitivity and false-positive rate (Spearman ρ = − 0.334, p = 0.062). Deeks’ test suggested potential small-study effects (p = 0.043). Conclusions: Circulating microRNA and lipidomic/metabolomic biomarkers demonstrate strong overall diagnostic performance for breast cancer detection; however, substantial heterogeneity and potential small-study effects limit their immediate clinical translation. Given that most included studies used retrospective case-control designs rather than prospective screening cohorts, these biomarkers are best regarded as investigational, complementary tools rather than replacements for mammography at this stage. Future large, prospective, standardized studies with harmonized pre-analytics and prespecified thresholds are needed to support the implementation of screening or triage pathways.

Breast cancer remains a global public health challenge. This study aimed to investigate the relationships between serum levels of insulin-like growth factor binding protein 3 (IGFBP-3), insulin-like growth factor 1 (IGF-1), the IGFBP-3 A-202C polymorphism and hormone receptor subtypes: estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) with respect to breast cancer risk in Palestinian women. A cross-sectional study was conducted on 112 newly diagnosed, histopathologically confirmed breast cancer patients. Data collection included structured interviews and laboratory analyses, including biochemical, genetic, and immunohistochemical assessments. The tumor tissue samples were analyzed for ER, PR, and HER-2 status. SPSS version 28 was used for all data analysis. A high prevalence of hormone receptor positivity was observed. Among the breast cancer patients, 87.5% were ER positive and 84.8% were PR positive. A total of 75.9% were HER-2 negative. The IGFBP-3 A-202C genotype is significantly associated with PR and combined ER/PR positivity ( p = 0.020). Patients with ER(+)/PR(+) status had significantly higher serum IGF-1 and IGFBP-3 levels ( p ≤ 0.001), with IGF-1 levels positively correlated with hormone receptor status ( r _s = 0.232, p ≤ 0.001) and advanced disease stages, moderately with Stage III ( r _s = 0.191, p ≤ 0.001) and weakly correlated with Stage IV ( r _s = 0.119, p = 0.029). These findings suggest that IGF-1 and IGFBP-3 may have potential as candidate biomarkers for breast cancer risk and progression. Integrating genetic, biochemical, and hormone receptor status provides novel insights into breast cancer biology and may support future research on personalized prevention and treatment strategies, particularly in resource-limited settings such as the Gaza Strip.

Breast cancer is the most common diagnosed cancer and the leading cause of cancer-related deaths among women globally. This study examined the impact of insulin-like growth factor binding protein-3 (IGFBP-3) A-202C polymorphism (rs2854744) on breast cancer risk and its association with insulin-like growth factor-1 (IGF-1) and IGFBP-3 serum levels among Palestinian women in the Gaza Strip. Understanding these genetic variants could guide the development of early detection strategies and personalized interventions for breast cancer in underrepresented populations. A case-control study involved 112 women with newly diagnosed breast cancer and 222 healthy controls. Genotyping of the IGFBP-3 A-202C polymorphism was performed using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP), and serum IGFBP-3 and IGF-1 levels were measured. The CC genotype of IGFBP-3 A-202C was observed in 70.5% of cases and 20.7% of controls, conferring a 16-fold increased breast cancer risk (OR=16.237; 95%CI 7.904, 33.356, p ≤ 0.001). The AC genotype was found in 19.6% of cases and 32.4% of controls, also associated with ~ 3-fold increased risk (OR=2.889; 95%CI 1.319, 6.325, p = 0.008). The CC genotype conferred a 28-fold increased risk in premenopausal women (OR=28.050; 95%CI 10.281, 76.527, p ≤ 0.001) and 5-fold in postmenopausal women (OR=5.333; 95%CI 1.711, 16.620, p = 0.004). Women with the CC genotype had the highest mean serum IGF-1 levels (116.49 ng/mL, p ≤ 0.001) and IGFBP-3 levels (3.76 µg/mL, p = 0.006) compared to those with the AA genotype. Positive correlations were observed between IGFBP-3 polymorphism and serum IGF-1 (r_s= 0.175, p ≤ 0.001) and IGFBP-3 levels (r_s = 0.164, p = 0.003). The IGFBP-3 A-202C polymorphism, especially the CC genotype, is strongly associated with elevated serum IGFBP-3 and IGF-1 levels and increased breast cancer risk, highlighting its potential as a biomarker for breast cancer screening and risk stratification. Further studies are needed to validate these findings in diverse populations.

Among the world, the most frequently discovered and fatal cancer in women is breast cancer (BC). From the perspective of public health, estimating the BC risk linked to dairy intake may aid in comp...

Objective: The purpose of this research was to look at the relationship between insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) levels and the risk for breast cancer (BC) among women in the Gaza Strip. Methods: This case-control study, which included 334 participants (112 women with BC as cases, and 222 women without BC as control), was conducted between January 2021 and August 2022. Research data for the cases were gathered at the Oncology Departments of the Gaza Strip’s two hospitals, “Al- Shifa Hospital and Turkish Palestinian Friendship Hospital,” as well as from the electronic records of the Screening Mammogram Unit at Al- Remal Clinic for controls. The information about the participants was gathered using a standardized questionnaire. The key variables related to BC were identified using multivariate logistic regression. Results: According to multivariate logistic regression, participants’ age was associated with an increase in the risk of BC (OR= 1.03; 95%CI, 1.007-1.060). There was an association between serum concentrations of fasting blood glucose (FBG) (OR= 1.027; 95% CI, 1.013–1.042), IGF-1 (OR= 1.010; 95% CI, 1.006–1.015), and the risk of BC, while there was no link between IGFBP-3 and the risk of BC. In an analysis of the risk according to menopausal status, premenopausal women were associated with an approximate 0.5 time decrease in risk of BC compared to women in post-menopause (OR= 0.428, 95% CI, 0.258, 0.710). Dairy product was also related to a decreased risk of BC. Conclusion: The results suggest that age, lower physical activity, increased levels of FBG, and IGF- 1 increase the BC risk among females in the Gaza Strip. Meanwhile, premenopausal women and dairy products are linked to a reduction in the risk of BC. Furthermore, no link was found between IGFBP-3 and BC risk. Improving early BC detection rates in the Gaza Strip necessitates preventative interventions and screening for BC in the public and healthcare sectors.