The role of the ESR1 gene in breast cancer: A comprehensive review of detailed analysis of biology, mutational landscapes, pathways, and therapeutic implications

The estrogen receptor alpha (ERα) protein, which is encoded by the ESR1 gene, is a key molecular factor that defines breast cancer. ERα activity regulates a complex program of hormonal activation and survival. ERα hypersensitivity, whether due to increased expression, activation, or aberrant activation, has been recognized as a crucial factor in disease progression and therapeutic resistance. The biological properties of ERα support conventional treatments and endocrine therapy inhibition. Moreover, they are pivotal for developing next-generation endocrine therapy strategies, including selective degraders and full antagonists. This article reviews the key roles of ERα in breast cancer and underscores recent developments in treatment strategies and their relevance to cancer. The goal is to improve the practical application of ER-driven breast cancer treatment. To summarize the multifaceted role of the ESR1 gene in breast cancer research, a comprehensive nonsystematic literature review was conducted. PubMed/MEDLINE and Web of Science were the primary electronic databases used. The search was not restricted by time to ensure the inclusion of historical landmarks and recent findings. The core search strategy employed keyword combinations focusing on “ ESR1 ” and “breast cancer,” further refining with terms, including “therapy,” “clinical diagnosis,” and “drug development,” to cover the breadth of the topic. Selection criteria focused on English-language peer-reviewed original and review articles. Case reports, non-peer-reviewed sources, and studies irrelevant to the clinical or therapeutic role of the ESR1 gene in breast cancer were excluded after screening the titles and abstracts.