EVALUATION OF CASCADE GENETIC TESTING FOR BRCA1/2 MUTATION CARRIERS IN ITALY: A SEMI-MARKOV SIMULATION STUDY
Author(s)
Carla Fornari, PhD1, Paolo Angelo Cortesi, PhD1, Lisa Ye, PhD1, Vittoria Fotia, MD2, Bernardo Pazbarboza, ScD1, Lorenzo G Mantovani, Prof1, Alberto Zambelli, Prof3.
1Research Centre on Public Health (CESP), University of Milano-Bicocca, Monza, Italy, 2Medical Oncology Department, ASST Papa Giovanni XXIII, Bergamo, Italy, 3Medical Oncology Department, ASST Papa Giovanni XXIII Hospital, Bergamo, Italy.
1Research Centre on Public Health (CESP), University of Milano-Bicocca, Monza, Italy, 2Medical Oncology Department, ASST Papa Giovanni XXIII, Bergamo, Italy, 3Medical Oncology Department, ASST Papa Giovanni XXIII Hospital, Bergamo, Italy.
OBJECTIVES: Early identification of individuals at high risk of developing cancer, such as BRCA 1/2 mutation carriers, is a major public health priority. This study aimed to evaluate effectiveness, timeframe, and costs of cascade testing for relatives of breast or ovarian cancer patients with BRCA 1/2 mutations in Italy as an alternative to population-wide genetic screening.
METHODS: Using a semi-Markov simulation model, we assessed the performance of cascade genetic testing by estimating identification timeframes, categorizing carriers (screen- vs. cancer-detected) accounting for mortality, alongside the required number of tests and associated testing costs. The model assumed annual cycles and a maximum of 100-year time-horizon. The model adopted the Italian National Health Service perspective, focusing strictly on the investment required to implement testing. The model incorporated Italian demographic data, age-specific mutation prevalence, cancer incidence, and vital statistics. We evaluated different cascade testing strategies, testing 1st, 1st-2nd, and 1st-3rd degree relatives, while varying uptake rates and population identification targets. A probabilistic sensitivity analysis was implemented to compute confidence intervals for estimates.
RESULTS: The model estimated a total of 113,164 BRCA1 and 251,492 BRCA2 mutation carriers within the 2024 Italian population. Identification timeframe was significantly influenced by target identification levels and test uptake. For a 70% BRCA1 identification target, the estimated time was 24, 21, and 18 years with 30%, 50%, and 70% uptake, respectively (first-degree relatives only). Testing up to third-degree relatives reduced these to 18, 13, and 9 years. Costs ranged from €6.6-13.6 million (1st degree) to €27.0-48.6 million (up to 3rd degree). For BRCA2, the pattern was consistent, but timelines were longer and costs higher, reflecting the larger carrier population.
CONCLUSIONS: Cascade testing represents an alternative strategy to identify healthy BRCA1/2 mutation carriers. These findings provide robust support for defining health policies in cancer prevention for high-risk individuals.
METHODS: Using a semi-Markov simulation model, we assessed the performance of cascade genetic testing by estimating identification timeframes, categorizing carriers (screen- vs. cancer-detected) accounting for mortality, alongside the required number of tests and associated testing costs. The model assumed annual cycles and a maximum of 100-year time-horizon. The model adopted the Italian National Health Service perspective, focusing strictly on the investment required to implement testing. The model incorporated Italian demographic data, age-specific mutation prevalence, cancer incidence, and vital statistics. We evaluated different cascade testing strategies, testing 1st, 1st-2nd, and 1st-3rd degree relatives, while varying uptake rates and population identification targets. A probabilistic sensitivity analysis was implemented to compute confidence intervals for estimates.
RESULTS: The model estimated a total of 113,164 BRCA1 and 251,492 BRCA2 mutation carriers within the 2024 Italian population. Identification timeframe was significantly influenced by target identification levels and test uptake. For a 70% BRCA1 identification target, the estimated time was 24, 21, and 18 years with 30%, 50%, and 70% uptake, respectively (first-degree relatives only). Testing up to third-degree relatives reduced these to 18, 13, and 9 years. Costs ranged from €6.6-13.6 million (1st degree) to €27.0-48.6 million (up to 3rd degree). For BRCA2, the pattern was consistent, but timelines were longer and costs higher, reflecting the larger carrier population.
CONCLUSIONS: Cascade testing represents an alternative strategy to identify healthy BRCA1/2 mutation carriers. These findings provide robust support for defining health policies in cancer prevention for high-risk individuals.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
EPH131
Topic
Economic Evaluation, Epidemiology & Public Health, Health Service Delivery & Process of Care
Topic Subcategory
Public Health
Disease
Oncology