OBJECTIVE

To evaluate the clinical efficacy of follow-up of healthy carriers of pathogenic germline variants associated with hereditary tumor syndromes and to determine the impact of personalized screening programs on early diagnosis of breast cancer.

MATERIAL AND METHODS

A prospective study included 986 participants who underwent genetic testing in the Loginov Moscow Clinical Scientific Center in 2018—2024. Among the participants, 551 people are healthy carriers of mutations (group A), 435 — patients with previously diagnosed malignant neoplasms (group B). Persons with germline mutations in BRCA1, BRCA2, CHEK2, PALB2, ATM, STK11 and TP53 genes were included. Monitoring was performed every 6 months, it included specialist consultations, mammography or magnetic resonance imaging, ultrasound examination of the mammary glands and pelvic organs. The primary outcome was the stage of detected breast cancer in mutation carriers compared to patients in whom disease has been diagnosed outside the screening program.

RESULTS

In healthy carriers of the mutations (group A, 551 people in total), 57 (10.3%) cases of cancer (predominantly breast cancer — 56 cases) have been detected during follow-up. Tumors were diagnosed at the stage I—II in 94.7% of the subjects, at the stage III — in 3.5%, cases of stage IV were not registered. Similar stages were revealed in 69.4% of the group B patients, the proportion of advanced stages (III—IV) amounted to 22%. BRCA1 c.5366dupC (p.Gln1777ProfsTer74) variant was the most frequent mutation. The proportion of triple-negative subtypes reached about 40% in both groups.

CONCLUSION

Personalized follow-up and screening programs for the carriers of pathogenic germline variants ensure predominant early breast cancer detection and form an effective prevention model for high genetic risk groups.