Pathological and Molecular Significance of HER2/neu Overexpression in Familial Breast Cancer Among Egyptian Women: A Comprehensive Study on Diagnostic and Prognostic Implications.

Purpose: Breast cancer remains the most prevalent malignancy among women worldwide, with a strikingly high incidence in Egypt, particularly in familial cases. This study aims to comprehensively elucidate the pathological and molecular significance of ERBB2 (HER2/neu) overexpression in Egyptian familial breast cancer, highlighting its role in tumor aggressiveness, immune evasion, and precision oncology. Methods: We enrolled 44 Egyptian breast cancer patients along with 35 daughters and 24 sisters (2013-2015, Mansoura University Hospital). Comprehensive analyses included serum biochemical assays, histopathological evaluation, immunohistochemical staining for ERBB2, and molecular detection of ERBB2 amplification using first-round and nested PCR. Associations with clinical, hormonal, and metabolic variables were also explored. Results: Serum biochemical profiling revealed significantly elevated ALT (6.6±0.55 U/mL), LDH (16.8±1.4 U/mL), and CA15 3 (160±13.33 U/mL), with reduced AST (2.6±0.22 U/mL) compared to controls ( Conclusion: Our findings highlight ERBB2 as a pivotal diagnostic and prognostic biomarker in Egyptian familial breast cancer and support integrating HER2-targeted therapies with immune checkpoint inhibitors and metabolic interventions. This approach could transform outcomes in high-risk familial cohorts. The study emphasizes the importance of genetic screening and precision medicine strategies that consider molecular, hormonal, and metabolic contexts in breast cancer care.