Abstract
Background
Integration of germline genetic testing with clinical genetic counselling is essential to guide prevention, surveillance, and personalised treatment in breast cancer. However, real-world implementation and access remain variable. We evaluated the impact of a structured genetic programme in a tertiary referral centre.
Methods
This retrospective study included patients with breast cancer undergoing germline testing and genetic counselling between January 2019 and July 2025 at the San Camillo-Forlanini Hospital (Rome), a referral hub for multiple oncology centres. Testing included BRCA1/2 (NGS/MLPA) and multigene panels, with variants classified per ACMG/AMP criteria. Clinical and treatment data were integrated with genetic findings.
Results
Among 4,573 patients, 325 carried pathogenic/likely pathogenic variants (7.1%, 95% CI: 6.4–7.9), mainly BRCA2 (37.0%) and BRCA1 (32.0%);87% were high/moderate-penetrance genes. Multigene testing increased detection of less common variants. Median age at diagnosis was 45 years. Uptake of preventive surgery was substantial, although variability persisted. Use of targeted therapies (e.g. PARP inhibitors) was inconsistent.Genetic counselling identified high-risk individuals eligible for intensified surveillance and risk-reducing strategies, including prophylactic bilateral mastectomy and salpingo-oophorectomy. Among carriers of high-risk variants, 86.4% underwent prophylactic or therapeutic mastectomy, reaching 94.1% in BRCA1 carriers. Five-year overall survival was 94%.
Conclusions
Integrated genetic testing and counselling support the implementation of effective prevention strategies in hereditary breast cancer, extending their impact beyond affected patients to unaffected relatives through cascade testing. However, gaps remain in equitable access and consistent application of personalised interventions. Strengthening coordinated, population-based genetic services is essential to maximise public health impact.
Key messages
• Systematic germline testing with counselling identifies a relevant proportion of hereditary breast cancer, enabling prevention strategies, organ-specific surveillance, and target treatments.
• Integrated services with cascade testing may ensure equitable access, reduce costs and duplication, and provide more standardised yet personalised care across centres, enhancing public health impact.