[Genetic predisposition to breast cancer]

Area of Science:

• Oncology
• Genetics
• Medical Diagnostics

Background:

• Breast cancer genetic testing has evolved over 30 years since BRCA1/2 identification.
• Ultra-high-throughput sequencing now analyzes eight predisposition genes.
• Tumor BRCA1/2 alterations increasingly guide testing, with 75% being constitutional.

Purpose of the Study:

• To review the evolution and current state of breast cancer predisposition testing.
• To highlight ongoing challenges and future directions in oncogenetics.
• To emphasize the crucial role of patients and families in advancing the field.

Main Methods:

• Review of advancements in genetic sequencing technologies.
• Analysis of expanding indications for genetic testing.
• Discussion of challenges in gene discovery, variant interpretation, and risk modeling.

Main Results:

• Expansion of genetic testing to include multiple predisposition genes.
• Emerging role of tumor genetic alterations in identifying constitutional mutations.
• Identification of key challenges: new gene validation, novel inactivation modes, variant classification, and multifactorial risk.

Conclusions:

• Despite progress, significant challenges persist in breast cancer genetic testing and risk assessment.
• Continued research is needed for new gene identification, variant interpretation, and personalized risk models.
• Patient and family involvement is vital for improving oncogenetic testing, support, and protection.