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Introduction <p><i>BARD1</i> germline pathogenic variants (gPV) have been primarily associated with moderate breast cancer risk but their rarity limits accurate risk assessment and tailored follow-up guidelines. Our study evaluates the association between <i>BARD1</i> gPV and breast cancer while exploring the role of BARD1 in mammary oncogenesis.</p> Materials and methods <p>In this case-control study, 7,309 women with breast cancer and no gPV identified in the French hereditary breast and ovarian cancer (HBOC) gene panel at the Institut Curie were compared to 57,681 female controls from the gnomAD European non-cancer database. Tumors were analyzed for biallelic <i>BARD1</i> inactivation and homologous recombination deficiency (HRD).</p> Results <p>A significant association was observed between <i>BARD1</i> gPV and breast cancer (<i>OR</i> = 5.2, 95% CI [3-8.9], <i>p</i> = 5.9 × 10<sup>− 9</sup>). Molecular data were obtained and interpretable for seven tumors. Among these, two triple-negative (TN) primary tumors exhibited both biallelic <i>BARD1</i> inactivation <i>via</i> loss of heterozygosity (LOH) and an HRD phenotype; one metastasis displayed LOH without HRD. All non-TN primary tumors lacked both biallelic inactivation and HRD.</p> Conclusion <p>We found a strong enrichment of <i>BARD1</i> gPV among women selected for personal and family history of breast cancer, reinforcing their relevance for genetic testing for suspected hereditary predisposition. Tumor analysis suggests a potential association between biallelic inactivation of <i>BARD1</i> and the HRD phenotype in TN primary breast tumors, providing new treatment perspectives.</p>

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BARD1 and breast cancer genetic predisposition: case–control study and HRD signature analysis

  • 期刊论文

  • 发表日期：

    2026年7月24日

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  • Marie-Florence Reveneau,
  • Antoine De Pauw,
  • Julien Masliah-Planchon,
  • Antoine Decees,
  • Salma Lakhlifi,
  • Justine Pasanisi,
  • Jessica Le Gall,
  • Mathias Schwartz,
  • Mélanie Pagès,
  • Elise Pierre-Noël,
  • Molka Sebai,
  • Sandrine M. Caputo,
  • Virginie Moncoutier,
  • Henrique Tenreiro,
  • Christelle Berthemin,
  • Jennifer Carrière,
  • Catherine Dubois d’Enghien,
  • Khadija Abidallah,
  • Christophe Guy,
  • Nicolas Fort,
  • Narjes Zaguia,
  • Anaïs Curto Taribo,
  • Olfa Trabelsi Grati,
  • Leslie Lori,
  • Arnaud Maillard,
  • Camille Benoist,
  • Eleonore Frouin,
  • Kévin Merchadou,
  • Fabien Quinquis,
  • Mathilde Filser,
  • Hélène Delhomelle,
  • Marine Le Mentec,
  • Mathilde Warcoin,
  • Ophélie Bertrand,
  • Marie-Charlotte Villy,
  • Claire Saule,
  • Emmanuelle Mouret-Fourme,
  • Marion Gauthier-Villars,
  • Bruno Buecher,
  • Tatiana Popova,
  • Marc-Henri Stern,
  • Victor Renault,
  • Eric Pasmant,
  • Dominique Stoppa-Lyonnet,
  • Chrystelle Colas,
  • Lisa Golmard

摘要

Introduction

BARD1 germline pathogenic variants (gPV) have been primarily associated with moderate breast cancer risk but their rarity limits accurate risk assessment and tailored follow-up guidelines. Our study evaluates the association between BARD1 gPV and breast cancer while exploring the role of BARD1 in mammary oncogenesis.

Materials and methods

In this case-control study, 7,309 women with breast cancer and no gPV identified in the French hereditary breast and ovarian cancer (HBOC) gene panel at the Institut Curie were compared to 57,681 female controls from the gnomAD European non-cancer database. Tumors were analyzed for biallelic BARD1 inactivation and homologous recombination deficiency (HRD).

Results

A significant association was observed between BARD1 gPV and breast cancer (OR = 5.2, 95% CI [3-8.9], p = 5.9 × 10− 9). Molecular data were obtained and interpretable for seven tumors. Among these, two triple-negative (TN) primary tumors exhibited both biallelic BARD1 inactivation via loss of heterozygosity (LOH) and an HRD phenotype; one metastasis displayed LOH without HRD. All non-TN primary tumors lacked both biallelic inactivation and HRD.

Conclusion

We found a strong enrichment of BARD1 gPV among women selected for personal and family history of breast cancer, reinforcing their relevance for genetic testing for suspected hereditary predisposition. Tumor analysis suggests a potential association between biallelic inactivation of BARD1 and the HRD phenotype in TN primary breast tumors, providing new treatment perspectives.