Prevalence of Somatic BReast CAncer Gene (BRCA) 1 and 2 Pathogenic Variants in Portuguese Metastatic Prostate Cancer
Tiago Barroso1, Carolina Monteiro1, Vanessa Patel1
1Medical Oncology, Unidade Local de Saude (ULS) Santa Maria, Lisbon, PRT.
Abstract:
Currently, poly adenosine diphosphate ribose polymerase inhibitors are used to treat metastatic prostate cancer (mPC) patients with somatic or germline pathogenic variants in genes related to homologous recombination repair deficiency. Testing for these variants is thus advisable, as test results can have implications for systemic treatment. Of those genes, the most relevant in clinical practice are BReast CAncer gene (BRCA) 1and 2. Despite no published data regarding the prevalence of germline and somatic variants in mPC Portuguese patients, practitioners have long felt that the prevalence of somatic BRCA1/2 variants in these patients is much lower than in previously studied populations. To estimate the prevalence of pathogenic BRCA1/2 variants, we fit a Bayesian hierarchical model with data from metastatic patients subject to universal testing and data from international cohorts. All 42 patients tested were negative for somatic BRCA1/2 pathogenic variants. This posterior estimate for the prevalence is 3.1% (95% credibility interval 0.3-10.3%), and we found a large dispersion between the prevalences of different populations. This estimate is much lower than the estimates in other published cohorts. We believe that testing recommendations should be tailored to country-specific prevalence. As such, we will continue to perform universal testing in an investigational context to decrease the uncertainty in our estimates and better establish the role of universal somatic testing in the Portuguese population.
Insights
Poly adenosine diphosphate ribose polymerase inhibitors treat metastatic prostate cancer (mPC) with BRCA1/2 variants. In Portugal, somatic BRCA1/2 variants are less common than previously thought, with an estimated prevalence of 3.1%.
Area of Science:
- Oncology
- Genetics
- Pharmacogenomics
Background:
- Poly adenosine diphosphate ribose polymerase (PARP) inhibitors are crucial for treating metastatic prostate cancer (mPC) in patients with homologous recombination repair (HRR) gene variants.
- BRCA1 and BRCA2 (BRCA1/2) are key HRR genes, and testing for pathogenic variants impacts treatment decisions.
- Limited data exists on the prevalence of germline and somatic BRCA1/2 variants in Portuguese mPC patients.
Purpose of the Study:
- To estimate the prevalence of pathogenic BRCA1/2 variants in Portuguese metastatic prostate cancer patients.
- To compare this prevalence with international data and inform country-specific testing recommendations.
Main Methods:
- A Bayesian hierarchical model was employed to estimate variant prevalence.
- Data included metastatic patients undergoing universal testing and international cohort data.
- Analysis focused on somatic and germline pathogenic variants in BRCA1/2 genes.
Main Results:
- No somatic BRCA1/2 pathogenic variants were detected in the 42 tested Portuguese mPC patients.
- The estimated posterior prevalence of pathogenic BRCA1/2 variants in this population is 3.1% (95% CrI: 0.3-10.3%).
- A significant dispersion in prevalence was observed across different populations, with the Portuguese estimate being notably lower than reported elsewhere.
Conclusions:
- The prevalence of somatic BRCA1/2 variants in Portuguese mPC patients appears lower than in other studied populations.
- Testing recommendations for PARP inhibitor eligibility should consider country-specific prevalence data.
- Continued universal testing in an investigational context is recommended to refine prevalence estimates for the Portuguese population.
