The Clinical and Pathological Profile of BRCA1 Gene Methylated Breast Cancer Women: A Meta-Analysis

SIMPLE SUMMARY: The aim of the present meta-analysis was to analyze all available studies reporting clinical characteristics of breast cancer gene 1 (BRCA1) gene hypermethylated breast cancer in women, and to pool the results in order to provide a unique clinical profile of this cancer setting population. Identifying the clinical profile of breast cancer in women harboring BRCA1 gene hypermethylation may help oncologists select a subgroup of patients who may be candidates for BRCA1 methylation assessment, thus, possibly enlarging the cancer population who may benefit from new target-therapy agents. Results showed that BRCA1 gene hypermethylation should be suspected in all breast cancer patients with advanced disease stages, positive lymph nodes, and premenopausal age at diagnosis. Multidisciplinary groups treating women with breast cancer should take into account the possibility of addressing patients with these characteristics with a BRCA1 gene methylation status analysis. ABSTRACT: Background: DNA aberrant hypermethylation is the major cause of transcriptional silencing of the breast cancer gene 1 (BRCA1) gene in sporadic breast cancer patients. The aim of the present meta-analysis was to analyze all available studies reporting clinical characteristics of BRCA1 gene hypermethylated breast cancer in women, and to pool the results to provide a unique clinical profile of this cancer population. Methods: On September 2020, a systematic literature search was performed. Data were retrieved from PubMed, MEDLINE, and Scopus by searching the terms: “BRCA*” AND “methyl*” AND “breast”. All studies evaluating the association between BRCA1 methylation status and breast cancer patients’ clinicopathological features were considered for inclusion. Results: 465 studies were retrieved. Thirty (6.4%) studies including 3985 patients met all selection criteria. The pooled analysis data revealed a significant correlation between BRCA1 gene hypermethylation and advanced breast cancer disease stage (OR = 0.75: 95% CI: 0.58–0.97; p = 0.03, fixed effects model), lymph nodes involvement (OR = 1.22: 95% CI: 1.01–1.48; p = 0.04, fixed effects model), and pre-menopausal status (OR = 1.34: 95% CI: 1.08–1.66; p = 0.008, fixed effects model). No association could be found between BRCA1 hypermethylation and tumor histology (OR = 0.78: 95% CI: 0.59–1.03; p = 0.08, fixed effects model), tumor grading (OR = 0.78: 95% CI :0.46–1.32; p = 0.36, fixed effects model), and breast cancer molecular classification (OR = 1.59: 95% CI: 0.68–3.72; p = 0.29, random effects model). Conclusions: hypermethylation of the BRCA1 gene significantly correlates with advanced breast cancer disease, lymph nodes involvement, and pre-menopausal cancer onset.