TY - JOUR

T1 - Pathological and Molecular Significance of HER2/neu Overexpression in Familial Breast Cancer Among Egyptian Women: A Comprehensive Study on Diagnostic and Prognostic Implications

AU - Abou-El-Naga, Amoura

AU - El Saied, Afaf

AU - Akl, Maher Monir

AU - AbdEL-Aziz, Sahar

N1 - Pathological and Molecular Significance of HER2/neu Overexpression in Familial Breast Cancer Among Egyptian Women: A Comprehensive Study on Diagnostic and Prognostic Implications / A. M. Abou-El-Naga, A. M. El Saied, M. M. Akl, S. A. Abd EL-Aziz // Advanced Pharmaceutical Bulletin. - 2025. - Т. 15. № 3. - С. 637-645. DOI 10.34172/apb.025.43866

PY - 2025/8/2

Y1 - 2025/8/2

N2 - Breast cancer, the most prevalent malignancy among women worldwide, exhibits a high incidence in Egypt, particularly in familial cases. This study investigates the pathological and molecular significance of ERBB2 (HER2/neu) overexpression in 44 Egyptian breast cancer patients, alongside 35 daughters and 24 sisters, recruited from Mansoura University Hospital (2013–2015). Serum biochemical markers, including alanine aminotransferase (ALT; 6.6 ± 0.55 U/mL), lactate dehydrogenase (LDH; 16.8 ± 1.4 U/mL), and cancer antigen 15-3 (CA15-3; 160 ± 13.33 U/mL), were significantly elevated, with reduced aspartate aminotransferase (AST; 2.6 ± 0.22 U/mL) compared to controls (P ≤ 0.05). Histopathological analysis revealed invasive ductal carcinoma with stromal desmoplasia, while immunohistochemical staining confirmed ERBB2 overexpression in >10% of tumor cells, correlating with aggressive tumor phenotypes. Molecularly, ERBB2 amplification was detected in 72% of patients via nested PCR, with daughters (17%) and sisters (20%) showing elevated frequencies. Notably, ERBB2 expression was higher in unmarried and pre-menopausal patients and those with diabetes or hypertension, suggesting hormonal and metabolic influences on ERBB2-driven oncogenesis via PI3K/AKT/mTOR and MAPK/ERK pathways. Additionally, ERBB2 may upregulate PD-L1, promoting immune evasion. These findings highlight ERBB2 as a critical diagnostic and prognostic biomarker in familial breast cancer, emphasizing the need for genetic screening and personalized therapies, such as HER2-targeted treatments combined with immune checkpoint inhibitors, to improve outcomes in high-risk Egyptian populations.

AB - Breast cancer, the most prevalent malignancy among women worldwide, exhibits a high incidence in Egypt, particularly in familial cases. This study investigates the pathological and molecular significance of ERBB2 (HER2/neu) overexpression in 44 Egyptian breast cancer patients, alongside 35 daughters and 24 sisters, recruited from Mansoura University Hospital (2013–2015). Serum biochemical markers, including alanine aminotransferase (ALT; 6.6 ± 0.55 U/mL), lactate dehydrogenase (LDH; 16.8 ± 1.4 U/mL), and cancer antigen 15-3 (CA15-3; 160 ± 13.33 U/mL), were significantly elevated, with reduced aspartate aminotransferase (AST; 2.6 ± 0.22 U/mL) compared to controls (P ≤ 0.05). Histopathological analysis revealed invasive ductal carcinoma with stromal desmoplasia, while immunohistochemical staining confirmed ERBB2 overexpression in >10% of tumor cells, correlating with aggressive tumor phenotypes. Molecularly, ERBB2 amplification was detected in 72% of patients via nested PCR, with daughters (17%) and sisters (20%) showing elevated frequencies. Notably, ERBB2 expression was higher in unmarried and pre-menopausal patients and those with diabetes or hypertension, suggesting hormonal and metabolic influences on ERBB2-driven oncogenesis via PI3K/AKT/mTOR and MAPK/ERK pathways. Additionally, ERBB2 may upregulate PD-L1, promoting immune evasion. These findings highlight ERBB2 as a critical diagnostic and prognostic biomarker in familial breast cancer, emphasizing the need for genetic screening and personalized therapies, such as HER2-targeted treatments combined with immune checkpoint inhibitors, to improve outcomes in high-risk Egyptian populations.

KW - HER2/neu

KW - ERBB2 amplification

KW - Familial breast cancer

KW - Oncogenic signaling

KW - Immune evasion

KW - Egyptian women

UR - https://www.mendeley.com/catalogue/df898822-6c6c-3a94-ab8b-ded2bba1dfb7/

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=105020301623&origin=inward

U2 - 10.34172/apb.025.43866

DO - 10.34172/apb.025.43866

M3 - Article

VL - 15

SP - 637

EP - 645

JO - Advanced Pharmaceutical Bulletin

JF - Advanced Pharmaceutical Bulletin

SN - 2228-5881

IS - 3

ER -