Abstract
BACKGROUND AND OBJECTIVE: Around 6% of female breast cancer (BC) cases are attributed to an inherited predisposition. Of the genes associated with an increased risk of BC, CHEK2 stands out as one of those most commonly identified. This review discusses various aspects of the association between the CHEK2 pathogenic variants (PVs) and BC. METHODS: This narrative review involved a comprehensive search of the literature in the PubMed, Embase, Google Scholar and the Latin American and the Caribbean Literature on Health Sciences (LILACS) databases. Original articles, reviews, meta-analyses, medical society consensuses and guidelines published in English were included. KEY CONTENT AND FINDINGS: This review highlights the complexity and challenges involved in managing CHEK2 PV carriers. When assessing the risk of BC in these individuals, family history and the type of mutation (either missense or protein-truncating) are relevant factors, emphasizing the need for personalized risk assessments. Few studies involving large cohorts and focusing on different outcomes were identified, specifically in CHEK2 PV carriers. Consequently, further studies with CHEK2 PV carriers are required that take genetic diversity into consideration, since the available data originate predominantly from cohorts with European ancestry. CONCLUSIONS: This review provides up-to-date evidence on the association between CHEK2 PVs and BC and its implications for the counseling and management of carriers.