Male breast cancer in Arab populations: a systematic review of molecular, genetic, and clinicopathologic characteristics.

Abstract

Background: Male breast cancer (MBC) accounts for less than 1% of all breast cancer cases, yet its incidence is increasing worldwide. Research on MBC remains limited, particularly in Arab populations, where molecular and genetic characteristics are poorly characterized. Improved understanding of MBC biology is essential to support region-specific, biology-driven management strategies.

Methods: This systematic review was registered in PROSPERO (CRD42024607019) and conducted according to PRISMA guidelines. PubMed, Embase, and Scopus were searched from inception to 28 December 2025. Eligible studies reported MBC cases from Arab countries and included data on molecular subtypes, receptor status, genetic alterations, and/or clinicopathologic characteristics. Data were extracted independently by four reviewers. Risk of bias was assessed using the Joanna Briggs Institute (JBI) critical appraisal tool, and findings were synthesized narratively with harmonization of tumor grade and stage where applicable.

Results: From 9,337 records, 54 studies comprising 1,534 MBC patients met the inclusion criteria. Invasive ductal carcinoma was the predominant histological subtype (92.6%). Among patients with reported intrinsic subtypes (n = 335), luminal A (45.7%) and luminal B (40.9%) accounted for over 86% of cases, whereas HER2-positive (4.8%) and triple-negative (8.4%) tumors were uncommon and triple-positive disease was rare (0.3%). Receptor status was reported for 1,031 patients, with high ER (71.5%) and PR (71.6%) positivity and low HER2 positivity (12.6%), alongside substantial heterogeneity in testing and reporting. Genetic data were available for 59 patients, most frequently identifying pathogenic truncating BRCA2 variants, although BRCA-negative cases were also reported. Surgery was the most reported treatment modality (n = 856), predominantly mastectomy-based, while endocrine therapy was frequently used and HER2-targeted therapy was infrequently reported.

Conclusion: MBC in Arab populations is predominantly hormone receptor-driven, characterized by luminal subtypes, high ER/PR positivity, and low HER2 expression. Genetic evidence, though limited, implicates BRCA2 as the most frequently reported susceptibility gene. These findings highlight the need for standardized molecular reporting and broader access to receptor profiling and genetic testing to support personalized, region-specific MBC management.