Abstract

Breast cancer, a complex and heterogeneous disease, is influenced by various genetic, hormonal, and environmental factors. Among these, the interplay between estrogen signaling and the tumor suppressor gene BRCA1 has garnered significant attention due to their individual roles in breast cancer etiology. Estrogen, a pivotal hormone in mammary gland development and function, has been associated with increased breast cancer risk, primarily through its mitogenic and pro-survival effects. On the other hand, BRCA1 plays a critical role in maintaining genomic stability and facilitating DNA repair processes. Mutations in BRCA1 are strongly linked to hereditary breast and ovarian cancers. Recent research suggests a multifaceted interaction between estrogen signaling and BRCA1 function, particularly in the context of DNA damage and repair mechanisms. This review delves into the intricate relationship between estrogen and BRCA1 deficiency, emphasizing their collaborative role in driving breast cancer-associated DNA damage and mutagenesis. We explore the molecular mechanisms through which estrogen can compromise BRCA1-mediated DNA repair, potentially leading to the accumulation of deleterious mutations. Furthermore, we discuss the implications of this synergistic interplay for therapeutic strategies targeting hormone receptor-positive breast cancers with BRCA1 mutations. Enhancing our understanding of how estrogen and BRCA1 deficiency coalesce to promote mutation-related DNA damage is crucial for developing more effective preventive and treatment approaches for breast cancer.