Primary Prevention and Early Detection of Hereditary Breast Cancer

Abstract

Background Primary prevention and early detection of hereditary breast cancer has been one of the main topics of breast cancer research in recent decades. The knowledge of risk factors for breast cancer has been increasing continuously just like the recommendations for risk management. Pathogenic germline variants (mutations, class IV/V) of risk genes are significant susceptibility factors in healthy individuals. At the same time, germline mutations serve as biomarkers for targeted therapy in breast cancer treatment. Therefore, management of healthy mutation carriers to enable primary prevention is in the focus as much as the consideration of pathogenic germline variants for therapeutic decisions. Since 1996, the German Consortium has provided quality-assured care for counselees and patients with familial burden of breast and ovarian cancer. Summary Currently, there are 23 university centers with over 100 cooperating DKG-certified breast and gynecological cancer centers. These centers provide standardized, evidence-based, and knowledge-generating care, which includes aspects of primary as well as secondary and tertiary prevention. An important aspect of quality assurance and development was the inclusion of the HBOC centers in the certification system of the German Cancer Society (GCS). Since 2020, the centers have been regularly audited and their quality standards continuously reviewed according to quality indicators adapted to the current state of research. The standard of care at GC-HBOC’ centers involves the evaluation as well as evolution of various aspects of care like inclusion criteria, identification of new risk genes, management of variants of unknown significance (VUS, class III), evaluation of risk-reducing options, intensified surveillance and communication of risks. Among these, the possibility of intensified surveillance in the GC-HBOC for early detection of breast cancer is an important component of individual risk management for many counselees. As has been shown in recent years, in carriers of pathogenic variants in high-risk genes this approach enables the detection of breast cancer at very early, more favorable stages although no reduction of mortality has been demonstrated yet. The key component of the intensified surveillance is annual contrast-enhanced breast MRI, supplemented by up to biannual breast ultrasound and mammography usually starting at age 40. Key Messages Apart from early detection, the central goal of care is the prevention of cancer. By utilizing individualized risk calculation, the optimal timeframe for risk-reducing surgery can be estimated, and counselees can be supported in reaching preference-sensitive decisions.

A contemporary review of breast cancer risk factors and the role of artificial intelligence

“…Genetic mutations, such as BRCA1 (Breast Cancer Gene 1) and BRCA2 (Breast Cancer Gene 2): Genetic mutations, particularly in BRCA1 and BRCA2 genes, significantly increase hereditary breast cancer risk. Studies like ( 92 ) analyze the role of germline CHEK2 (Checkpoint Kinase 2) variants, while ( 97 ) advocate personalized prevention strategies ( 98 ). identifies genetic loci associated with contralateral breast cancer risk, and ( 3 ) explores molecular links between obesity and breast cancer.…”