Genetic profiling of healthy family members of breast and ovarian cancer patients in Estonia
TL;DR
The findings highlight the value of genetic testing in identifying at-risk individuals among HFMs of BCOC patients and the expansion of HFM testing in Estonia reflects increased public awareness and clinical integration of genetic risk assessment in cancer prevention strategies.
Abstract
Background Genetic testing for likely pathogenic/pathogenic variants (PV) in BRCA1, BRCA2, and other cancer-associated genes plays a critical role in the diagnosis, prognosis, and management of breast and ovarian cancer (BCOC). Extending testing to healthy family members (HFM) of affected individuals enables early prevention strategies and timely referrals for enhanced screening, thereby improving cancer risk management. This study aimed to characterize the demographic profile and genetic findings among HFMs of BCOC patients in Estonia within routine clinical practice. Methods A retrospective analysis was conducted on 3,472 HFMs who underwent genetic testing. Demographic data were collected, and the presence of PVs was assessed. Statistical comparisons were made between individuals with and without known familial PVs, and between male and female participants, using descriptive statistics and proportion comparisons. Results Of the 3,472 HFMs tested, 87.6% were female and 12.4% male, with a mean age of 41.1 ± 13.0 years. Notably, 78.6% were younger than 51 years, the typical age for initiating standard screening. PVs were identified in 683 individuals (19.7%). Among those with a known familial PV (n = 1,009), 41.8% were carriers, compared to 8.0% among those without a known familial PV (n = 2,408). Males were more likely to be tested when a familial PV was known (26.6%) than when it was not (6.6%), and 34.0% of tested males were PV carriers. PVs were found in 23 different genes, with BRCA1/2 accounting for 58.4% of all PVs, followed by ATM, BRIP1, CHEK2, and PALB2. Conclusion The findings highlight the value of genetic testing in identifying at-risk individuals among HFMs of BCOC patients. The predominance of BRCA1/2 variants and the significant detection rate among younger individuals underscore the importance of early testing. The expansion of HFM testing in Estonia reflects increased public awareness and clinical integration of genetic risk assessment in cancer prevention strategies.