25 years of impact in hereditary breast and ovarian cancer awareness and management in Latvia

25 years ago, RSU began actively participating in the European Commission’s 5th Framework Research Project on ‘Development of Cancer Family Syndrome Registries in Eastern Europe’ due to its close European partners. As a result of the project, predecessor of the RSU Institute of Oncology and Molecular Genetics (IOMG) – Hereditary Cancer Institute – was established in 2001. Since then, it has been a leading institution promoting advances in hereditary cancer research, awareness, and management in Latvia. 

An early multi-centre epidemiological study of the three most common recurrent BRCA1 variants identified in Eastern Europe also confirmed their high frequency among cases of breast and ovarian cancer in Latvia. This finding underlined the fact that a large proportion of carriers and individuals at very high-risk could be identified through an affordable and accessible genetic test. These results led to the establishment of the country’s first hereditary cancer outpatient clinic, a very innovative step for many European Union member states and the rest of the world in 2002. In the framework of the PHARE Cross Boarder Cooperation Programme, a Hereditary cancer information and prevention centre was developed, and a series of hereditary cancer awareness campaigns were launched for professionals (family physicians, genecologists) and the broader public. These campaigns initiated identification and risk reduction of high-risk individuals.

In the emerging era of Next-generation sequencing (NGS), the role of testing for recurrent BRCA1/2 variants started to lose its importance in many countries. However, the number of RSU studies on the BRCA1/2 spectrum justified a two-stage universal testing approach for all consecutive breast and ovarian cancer cases in Latvia, as the two most frequent recurrent variants were identified in as much as 3.8 % and 10 % of the breast and ovarian cohorts, respectively. Complete BRCA1/2 testing, covered by the National Health System, was performed only in cases when recurrent variants were not found and the Manchester Score indicated a high probability of mutation. This is another diagnostic algorithm that was validated by the IOMG team in 2018 to improve the cost-effectiveness of genetic testing strategies.

An unexpected milestone discovery was published in 2021 due to a comprehensive BRCA1/2 study of unsolved hereditary breast and ovarian cancer cases by NGS. The study described a high frequency (> 2 % among unselected breast cancers) of a previously undetected pathogenic variant of BRCA1 (c.5117G > A) due to its unclear pathogenicity. This finding directly impacted the industry, prompting an immediate adjustment to the BRCA1/2 recurrent variants test, offered by several commercial laboratories. Consequently, dozens of previously undetected BRCA1 carriers now have access to timely, personalised management and prevention.

For years, the motto of the IOMG team has been similar to that of Mary-Claire King, the famous scientist who discovered the BRCA1 gene. She said, ‘Identifying a woman as a carrier only after she develops cancer is a failure of cancer prevention.’ This led IOMG researchers to conduct a cutting-edge pilot study in 2023 on the feasibility of hereditary breast and ovarian cancer risk genetic population screening using a digital communication platform. This study was funded by a socially responsible private company, Lindex. The digital platform solution was developed by the IT startup, Longenesis, and the E. Gulbja commercial laboratory kindly offered its logistic services to ensure easy sample collection across the country. The pilot study confirmed the need for more accessible genetic testing for individuals with a family history of breast and ovarian cancer. More than 500 unaffected women were enrolled via an online digital platform, and BRCA1/2 carriers were identified in up to 1.5 % of cases. The results of the pilot study provided solid evidence of a successful digital medicine approach to identifying very high-risk individuals. Furthermore, the study also showed (by using validated questionnaires for patients before and after genetic testing) that genetic testing does not significantly affect patients’ anxiety and depression levels. The results of the study have been disseminated and highly appreciated internationally, including at the ESHG (European Society of Human Genetics) 2025 annual meeting.

Through close cooperation with the ERN GENTURIS (European Reference Network for all patients with one of the rare genetic tumour risk syndromes) IOMG researchers have played an active role in endorsing the ESMO (European Society for Medical Oncology) hereditary breast and ovarian cancer guidelines and developing the PTEN hamartoma tumor syndrome guidelines. Collaborative efforts with national stakeholders, such as university hospitals, the Ministry of Health and the National Health Service, have led to the local adoption of BRCA1/2 clinical pathways.

RSU IOMG’s membership in the ENIGMA (Evidence-Based Network for the Interpretation of Germline Mutant Alleles) and CIMBA (The Consortium of Investigators of Modifiers of BRCA1/2), as well as the BCAC (The Breast Cancer Association Consortium), is a strong proof of its wide international networking, which resulted in hosting the annual Consortia meeting in Rīga in 2024.

In conclusion, hundreds of breasts and ovarian cancer cases have been prevented by the research and awareness activities of IOMG. Hundreds of mutation carriers have undergone risk-reductive bilateral Salpingo-oophorectomies and mastectomies. In addition, the scientists of RSU IOMG initiated an annual breast MRI surveillance programme 5 years ago, which has considerably improved the early diagnosis of high-risk individuals and has given them access to personalised targeted therapies. The RSU team’s hereditary cancer research and awareness activities have resulted not only in decreased breast and ovarian cancer morbidity and mortality, but they have also considerably reduced direct and indirect public healthcare costs for managing advanced-stage breast and ovarian cancers. These activities have also greatly improved the quality of life for those in whose cancer has been prevented or successfully cured.

As a result of these activities, RSU now holds a unique hereditary cancer registry and biobank. It contains more than 40,000 family cancer histories and 10,000 DNA samples from individuals with and without cancer. Additionally, it contains more than 1,000 detailed clinical records on individuals who carry pathogenic variants in hereditary breast and ovarian cancer susceptibility genes. This registry and biobank form a firm foundation for future research and development in this field.