Gustavo Tadeu Freitas Uchôa Matheus

Breast cancer incidence and subtype patterns among BRCA-mutated ovarian cancer patients: a systematic review and meta-analysis

BRCA1 and BRCA2 are tumor suppressor genes essential for DNA repair. Mutations in these genes significantly increase breast (BC) and ovarian cancer (OC) risk, with BRCA1-positive facing a 70% BC and 40% OC lifetime risk. While guidelines for BRCA-positive are well established, recommendations for BC surveillance in BRCA-patients already diagnosed with OC remain limited. This meta-analysis evaluates BC risk post-OC in BRCA-mutated women. A systematic search of PubMed, Embase, and the Cochrane Library was performed. Single-arm outcomes were pooled using meta-analysis of proportions, and survival data were synthesized using hazard ratio (HR), both with 95% confidence intervals (CIs). Heterogeneity was assessed using the I² statistic. All analyses were conducted in R (version 4.3.2). A total of 2380 patients from 10 retrospective cohort studies were included. Among them, 181 (8%; 95% CI: 6%-11%) developed BC post-OC, with similar rates observed for BRCA1 and BRCA2-mutated (9%; 95% CI: 7%-12%). In overall survival analysis, BRCA-mutated patients who developed BC after OC had significantly improved outcomes compared to those with OC only (HR = 0.4657; P < 0.001). This meta-analysis underscores the need for tailored BC surveillance and evidence-based screening guidelines in BRCA-mutated OC survivors.

Impact of TP53 somatic mutations on prognosis in endometrial cancer: a systematic review and meta-analysis

Endometrial cancer (EC) is the sixth most common female cancer and may rank fourth in cancer mortality by 2040. TP53 mutations and aberrant p53 expression are associated to aggressive tumor subtypes and poor prognosis, reducing overall survival (OS), disease-free survival, recurrence rates (RcR) and Mortality Risk (MR). The prognostic impact of TP53 mutations in EC remains unclear. A systematic search was conducted in PubMed, Embase, and the Cochrane Library. Hazard ratios (HR) and Risk Ratios (RR) with 95% confidence intervals (CI) were combined using random-effects models. Analyses were conducted in RStudio (v4.4.1), and heterogeneity was evaluated using the I Twenty-four studies comprising 5462 EC patients were included. TP53 mutations and aberrant p53 expression were associated with poorer outcomes. For OS, TP53 mutations had an HR of 2.27 (95% CI 1.47-3.49) and aberrant p53 had an HR of 5.01 (95% CI 2.44-10.30). For DFS, TP53 mutations had an HR of 4.20 (95% CI 1.79-9.86), while aberrant p53 had an HR of 2.17 (95% CI 1.27-3.72). TP53 mutations also increased RcR (RR: 2.88; 95% CI 2.18-3.80) and MR (RR: 2.33; 95% CI 1.11-4.88). Aberrant p53 showed a non-significant trend for recurrence (RR: 3.54; 95% CI 0.95-13.10). TP53 mutations and abnormal p53 expression in EC patients predict a poorer prognosis, characterized by increased RcR and MR, as well as lower DFS and OS.