Hereditary Breast Cancer in Romania-Molecular Particularities and Genetic Counseling Challenges in an Eastern European Country.

In Romania, breast cancer (BC) is the most common malignancy in women. However, there is limited data on the prevalence of predisposing germline mutations in the population in the era of precision medicine, where molecular testing has become an indispensable tool in cancer diagnosis, prognosis, and therapeutics. Therefore, we conducted a retrospective study to determine the prevalence, mutational spectrum, and histopathological prediction factors for hereditary breast cancer (HBC) in Romania. A cohort of 411 women diagnosed with BC selected upon NCCN v.1.2020 guidelines underwent an 84-gene NGS-based panel testing for breast cancer risk assessment during 2018-2022 in the Department of Oncogenetics of the Oncological Institute of Cluj-Napoca, Romania. A total of 135 (33%) patients presented pathogenic mutations in 19 genes. The prevalence of genetic variants was determined, and demographic and clinicopathological characteristics were analyzed. We observed differences among BRCA and non-BRCA carriers regarding family history of cancer, age of onset, and histopathological subtypes. Triple-negative (TN) tumors were more often BRCA1 positive, unlike BRCA2 positive tumors, which were more often the Luminal B subtype. The most frequent non-BRCA mutations were found in CHEK2, ATM, and PALB2, and several recurrent variants were identified for each gene. Unlike other European countries, germline testing for HBC is still limited due to the high costs and is not covered by the National Health System (NSH), thus leading to significant discrepancies related to the screening and prophylaxis of cancer.

Prevalence of positive screening test results and agreement between cytology and human papillomavirus testing in primary cervical cancer screening in North-Western Romania.

Using data from a pilot study conducted in North-Western Romania, we aimed to estimate the prevalence of abnormal cytology and positive high-risk human papillomavirus (hr-HPV) test results in an ethnically diverse screening population and to assess the agreement between cytology and hr-HPV testing to evaluate the feasibility of integrating the latter as a primary test in the national cervical cancer screening program. The cross-sectional pilot study included Roma women, other ethnic minorities, and women in rural remote areas. Samples were taken for liquid-based cytology and hr-HPV testing (Hybrid Capture 2 DNA test) by a mobile health unit. The prevalence of positive screening results and the agreement between cytology and hr-HPV testing were estimated by κ coefficient. A total of 1019 women were included in the study. The population prevalence of positive screening results was similar for both tests (12%). The prevalence of abnormal cytology increased with increasing age, whereas the prevalence of positive hr-HPV test showed a bimodal age pattern. Substantial differences in the prevalence of abnormal cytology were found by ethnicity, with highest prevalence in Romanian women (14%), followed by Roma women (6%) and women of other ethnicities (5%) (P = 0.002). Similar ethnic differences in the prevalence of positive hr-HPV test were not observed. The overall agreement of positive screening results between the two methods was fair (κ = 0.25; 95% confidence interval = 0.18-0.30, P < 0.001) and ranged from poor to substantial depending on the age group. The prevalence of abnormal cytology result was high and similar to the prevalence of positive hr-HPV test result, which could allow for the implementation of hr-HPV testing as a primary test in the cervical cancer screening program in Romania.