COMPARISON OF EXPRESSION OF HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 (HER-2) IN BREAST CANCER TISSUE AND AXILLARY LYMPH NODES, AND OTHER PROGNOSTIC FACTORS AND OUTCOMES IN THE NORTHWEST PART OF PAKISTAN

Abstract

Background: Breast cancer is a heterogeneous disease with rising incidence and mortality worldwide. It is influenced by environmental, genetic, reproductive, dietary, and lifestyle factors and presents with diverse molecular subtypes, clinical features, and treatment outcomes. Tumor size, grade, lymph node involvement, and hormone receptor status are key prognostic indicators. This study evaluated biomarkers, specifically HER-2, in primary breast tumors and corresponding axillary lymph nodes, and examined their association with other prognostic factors.

Methods: In this prospective study, HER-2 status in breast tumors and matched axillary lymph nodes was assessed using immunohistochemistry (IHC) according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines. Scores 0 and 1+ were labeled as negative, scores 2+ as equivocal, and scores 3+ as positive. A total of 110 mastectomy specimens with axillary dissection were analyzed for HER-2 concordance between primary tumors and lymph nodes. Patients were followed for one year, until December 2021. Associations between HER-2 expression and prognostic factors were analyzed using SPSS version 27.

Results: The mean age at diagnosis was 48 years. Most women were married (89%) and multiparous, with equal distribution between pre- and postmenopausal status. A majority had breastfed their children. Seventy-nine percent received neoadjuvant chemotherapy, and 7.2% had a family history of breast cancer. The most common presenting complaints were a painless lump (27%) and a painful lump (20%). Average tumor size was 3.1 cm, with 78% being invasive ductal carcinoma and 60% being grade 2 tumors. Fifty-six percent were metastasized to the axillary lymph node at the time of diagnosis. HER-2 (3+) overexpression was observed in 17% of primary tumors and 12.7% of axillary lymph nodes. Concordance in HER-2 (3+) expression between primary tumors and lymph nodes was observed in 70% of cases. One discordant case was noted (r = 0.510, p = 0.01). Among HER-2 (3+) cases, 82.3% had lymph node metastasis detected by H&E staining, and one additional case was identified via IHC (r = 0.353, p = 0.001). Among HER-2–positive cases, 58.8% were grade 2 tumors; no cases were grade 1 (p = 0.01, r = 0.526). HER-2 expression showed a weak positive correlation with tumor size (r = 0.373, p = 0.01). Sixty-six percent were diagnosed as early stage (Ⅰ and Ⅱ), and of all HER-2 positive cases, 53% were early-stage disease (r=.310, p = .01HER-2 expression was significantly correlated with age (r = 0.441, p = 0.01), with most HER-2 positive cases occurring in patients under 60 years. Conclusion: HER-2 overexpression was more common in younger patients and associated with greater metastatic potential. While most cases showed concordance in HER-2 expression between primary tumors and lymph nodes, a few discordant cases were observed. These may affect treatment planning and highlight the importance of assessing both sites for accurate diagnosis and therapy selection.