npj Breast Cancer (2026): Constitutional BRCA1 Methylation is Associated with High Level of Tumoral BRCA1 Methylation and Homologous Recombination Deficiency in Triple-Negative Breast Cancer Using Methyl Detect Technology

Background: This prospective study analyzed paired tumor and blood samples from 136 triple-negative breast cancer (TNBC) patients from the SCANDARE study (NCT03017573). To evaluate constitutional and tumoral BRCA1 promoter methylation status, the semi-quantitative methylation-sensitive high-resolution melting (MS-HRM) EpiMelt assay from MethylDetect ApS (Aalborg, Denmark) was utilized, targeting six CpG sites of the core BRCA1 promoter (c.-133 to c.-96).
Key Finding: Constitutional BRCA1 methylation was detected in 20.6% of patients, and tumoral methylation in 31.6%. In cases with constitutional BRCA1 methylation, tumoral methylation levels increased markedly, with 89% of high-methylation tumors (≥ 50%) associated with a Loss of Heterozygosity (LOH). Furthermore, tumors with BRCA1 promoter methylation consistently exhibited high homologous recombination deficiency (HRD) scores, which were comparable to those with pathogenic homologous recombination repair (HRR) gene variants (p < 0.001).
Conclusion: Constitutional and somatic BRCA1 promoter methylation are closely associated with high levels of tumoral methylation and homologous recombination deficiency in TNBC. These findings support integrating constitutional and tumoral BRCA1 methylation assessment into clinical workflows to improve patient stratification and precision oncology applications.
Original Article & Authors: Published in npj Breast Cancer (2026), authored by Justine Pasanisi, Constance Lamy, Lolita Lecompte, Sophie Vacher, Mathias Schwartz, Abderaouf Hamza, Sandrine M. Caputo, Sabrina Ibadioune, Laura Courtois, Frédérique Berger, Vincent Cockenpot, Sylvain Baulande, Jean-Yves Pierga, Celine Callens, Samia Melaabi, Chrystelle Colas, Eric Pasmant, Maud Kamal, Célia Dupain, Nicolas Servant, Christophe Le Tourneau, and Ivan Bièche. Research institutions and departments include the Department of Genetics, Department of Drug Development and Innovation (D3i), Department of Biometry, Department of Pathology, Genomics of Excellence (ICGex) Platform, and Department of Medical Oncology at Institut Curie (Paris and Saint-Cloud, France), as well as Computational Oncology at PSL Research University, Mines Paris Tech, INSERM 1331, and Paris Cité University.

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