Abstract

HER2-positive metastatic breast cancer represents a distinct subtype of breast cancer with aggressive clinical behavior. While the overexpression of human epidermal growth factor receptor 2 (HER2) is a hallmark of this subtype, its heterogeneity necessitates a more nuanced understanding to guide treatment decisions. Beyond traditional hormone receptor status, identifying comprehensive biomarkers is crucial for optimizing the management of HER2-positive metastatic breast cancer. This abstract explores the evolving landscape of biomarkers in this context. In recent years, research has highlighted the significance of several biomarkers that offer a deeper insight into the intricacies of HER2-positive metastatic breast cancer. Notably, beyond the status of estrogen receptor (ER) and progesterone receptor (PR), additional markers such as PIK3CA mutations, PTEN loss, and the tumor-infiltrating lymphocytes (TILs) density have emerged as pivotal factors in tailoring therapeutic strategies. PIK3CA mutations have been found to modulate the response to HER2-targeted therapies and endocrine therapies, shedding light on the crosstalk between signaling pathways. Concurrently, PTEN loss has been associated with resistance to HER2- targeted agents, offering a crucial avenue for patient stratification. Furthermore, TILs, as indicators of the immune microenvironment, play a role in predicting response to immunotherapies in HER2-positive metastatic breast cancer. In addition to genomic and immune markers, liquid biopsies have gained prominence as a non-invasive approach to detect HER2 alterations and monitor treatment response. Circulating tumor DNA (ctDNA) and exosomes markers can provide real-time information about disease progression and emerging resistance mechanisms. This abstract emphasizes the evolving significance of biomarkers that extend beyond hormone receptor status in HER2-positive metastatic breast cancer. Understanding the molecular and immunological landscape of this subtype is essential for individualizing treatment and optimizing patient outcomes. In an era of precision oncology, these comprehensive biomarkers offer a promising path towards improving the management of HER2-positive metastatic breast cancer patients, ultimately enhancing their quality of life and overall survival.