Thirty Years of BRCA1: Mechanistic Insights and Their Impact on Mutation Carriers

Abstract Thirty years ago, the cloning of the first breast cancer susceptibility gene, BRCA1, marked a milestone in our understanding of hereditary breast and ovarian cancers. This discovery initiated extensive research into DNA repair mechanisms, BRCA1-associated tumorigenesis, and therapeutic interventions. Despite these advances, critical questions remain unanswered, such as the evolution of BRCA1-associated tumors and their tissue specificity. These issues hinder the development of effective treatment and prevention strategies, which ultimately aim to improve the quality of life for BRCA1 mutation carriers. In this review, we discuss current knowledge, identify existing gaps, and suggest possible avenues to tackle these challenges. Significance: Here, we explore the impact of three decades of BRCA1 research on the lives of mutation carriers and propose strategies to improve the prevention and treatment of BRCA1-associated cancer.