Comprehensive Screening for Early Cancer Detection in Individuals With Genetic Predisposition

To evaluate the effectiveness of a comprehensive screening program for individuals with genetic predisposition to cancer, focusing on early detection and improved treatment outcomes through systematic clinical, instrumental, and laboratory monitoring of pathogenic/likely pathogenic (P/LP) variant carriers.

The registry screening program included two groups: (1) patients with cancer with confirmed germline P/LP variants associated with cancer predisposition, and (2) healthy individuals carrying germline P/LP variants predisposing to cancer development. In total, 816 participants were included. Participants underwent routine screening, including medical history recording, and instrumental and laboratory investigations accompanied by consultations of different specialists. The study compared the age and stage of the disease at the time of cancer diagnosis between healthy P/LP variant carriers (Group A, n = 554) and patients with cancer (Group B, n = 262).

Among the 554 healthy P/LP variant carriers in Group A, 57 patients of cancer (10.2%) were identified, predominantly breast and ovarian cancers (Group A1). In Group A1, 96.4% of detected cancers were at stages I to II. The average age at diagnosis in Group A1 was 52 ± 12 years, with 35% of patients detected within 6 months, 58% within 1 year, and 7% within 1.5 years after inclusion of an individual into the screening program. In Group B1 (191 patients with breast cancer), 20.9% were diagnosed at stages III to IV. Notably, 27% of aggressive molecular biological subtypes of breast cancer (Luminal B and triple-negative) were identified at stage I in Group A1, and the most common BRCA1 variant was c.5266dupC (rs80357906), accounting for 64.3% of such patients.

The comprehensive screening program demonstrated the effectiveness of early detection of malignancies in individuals with genetic predisposition to cancer development. The identification of a significant proportion of early-stage cancers, particularly aggressive subtypes, highlights the importance of tailored screening strategies for the cohort of patients at high risk of cancer development.