ArticleBMC cancer2025
The difference in contralateral breast cancer and ovarian cancer risks for BRCA1 founder variant (c.5266dup, c.4035del) carriers with primary breast cancer.
Article in BMC cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeTo compare the risks of CBC and OC following a diagnosis of PBC in carriers of founder germline PV's of BRCA1 gene (c.5266dup and c.4035del), and to evaluate the impact of age at PBC diagnosis on subsequent CBC and OC risks. SUBJECTS AND
methodsThis retrospective bicentric cohort study included 1,364 female BRCA1 PV carriers diagnosed with and PBC. The control cohort comprised 11,350 unselected female PBC cases without known BRCA1 PVs. Follow-up begun at PBC diagnosis and continued until CBC or OC occurrence, censoring at risk-reducing surgery, death, or last follow-up. Risks were estimated using Kaplan-Meier analysis, log-rank testing and Cox proportional hazards modelling.
resultsThe 10-year cumulative risk of CBC was 3.3% in controls, 25.0% in the c.5266dup carriers, and 13.1% in the c.4035del carriers. BRCA1 PV carriers had significantly higher CBC risks compared with controls (p < 0.001), with c.5266dup conferring greater risk than c.4035del (p = 0.045). Age < 40 years at PBC diagnosis independently increased CBC risk (HR 2.06, 95% CI 1.83-2.29, p < 0.001). For OC, the 10-year cumulative risk was 1.0% in controls, 13.0% in the c.5266dup carriers and 22.1% in the c.4035del carriers. BRCA1 PV carriers had higher OC risks compared with controls (p < 0.001), and c.4035del conferred higher risk than c.5266dup, (p = 0.043). Age < 40 years at PBC did not significantly affect OC risk (HR 1.03, 95% CI 0.77-1.29, p = 0.23).
conclusionBoth BRCA1 founder PVs confer substantially increased risks of CBC and OC compared with the general breast cancer population. The PV c.5266dup is associated with relatively higher CBC risk and lower OC risk, whereas PV c.4035del is associated with relatively lower CBC risk but higher OC risk. Age < 40 years at PBC further increases CBC risk, but does not influence OC risk. These findings highlight the importance of PV location in refining individualized risk-reduction strategies for BRCA1 carriers.
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