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.
M. Tooming, Kadri Rekker, K. Toome et al.· Frontiers in Genetics· 0 citations
Background Population-based mammographic screening is primarily age-based. However, breast cancer risk is multifactorial, and women may benefit from personalized risk-based screening. This pilot study aimed to explore the use of polygenic risk score (PRS) as a tool for risk stratification in personalized screening. Methods We included 80 women aged 40–49 years referred for clinical mammography. Exclusion criteria were prior breast cancer or premalignant breast disease, and previous genetic testing. After DNA collection, PRS was calculated from 2805 Single Nucleotide Polymorphisms (SNPs). Screening recommendations were based on each participant’s relative 10-year breast cancer risk estimated from PRS and compared with the 10-year risk of an average woman of the same age. Women with a self-reported family history of cancer meeting standard criteria were referred for gene panel testing for pathogenic variants in high-risk genes. A follow up questionnaire regarding participants’ experiences was distributed 6–9 months after PRS testing. Results Mean age was 45.2 years (SD 2.8). Mean relative 10-year breast cancer risk was 1.18 (SD 0.57). Based on PRS, 40 participants were recommended standard biennial screening 50–69 years, while 40 were advised to begin biennial screening before age 50. Among these, 7 were recommended annual mammography from when their 10-year risk reached twice that of an average 50-year-old. Twenty-one women underwent gene panel testing; no pathogenic variants in breast cancer genes were identified. Five women were advised annual mammography from 40–60 years due to family history of breast cancer, regardless of PRS. Most respondents viewed breast cancer risk assessment positively and did not report increased anxiety after testing. Conclusions In this pilot cohort, PRS-based risk stratification led to earlier or more intensive screening recommendations in half of the participants, while family history also influenced management.
T. Hovda, S. Sõber, P. Padrik et al.· PLoS ONE· 0 citations