Prevalence of Pathogenic Germline Variants in Women with Non-Familial Unilateral Triple-Negative Breast Cancer

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Kerstin Rhiem - , University of Cologne (Author)
  • Silke Zachariae - , Leipzig University (Author)
  • Anke Waha - , University of Cologne (Author)
  • Sabine Grill - , Technical University of Munich (Author)
  • Anna Hester - , Ludwig Maximilian University of Munich (Author)
  • Michael Golatta - , Heidelberg University  (Author)
  • Marion Van MacKelenbergh - , Kiel University (Author)
  • Tanja Fehm - , Heinrich Heine University Düsseldorf (Author)
  • Tanja Schlaiß - , University of Würzburg (Author)
  • Tim Ripperger - , Hannover Medical School (MHH) (Author)
  • Susanne Ledig - , University of Münster (Author)
  • Cornelia Meisel - , Department of Gynecology and Obstetrics (Author)
  • Dorothee Speiser - , Charité – Universitätsmedizin Berlin (Author)
  • Kristina Veselinovic - , Ulm University (Author)
  • Christopher Schröder - , University of Tübingen (Author)
  • Isabell Witzel - , University of Hamburg (Author)
  • Julia Gallwas - , University of Göttingen (Author)
  • Bernhard H.F. Weber - , University of Regensburg (Author)
  • Christine Solbach - , University Hospital Frankfurt (Author)
  • Bariyhe Aktas - , Leipzig University (Author)
  • Eric Hahnen - , University of Cologne (Author)
  • Christoph Engel - , Leipzig University (Author)
  • Rita Schmutzler - , University of Cologne (Author)

Abstract

Introduction: International guidelines recommend genetic testing for women with familial breast cancer at an expected prevalence of pathogenic germline variants (PVs) of at least 10%. In a study sample of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC), we have previously shown that women with TNBC diagnosed before the age of 50 years but without a family history of breast or ovarian cancer (sTNBC) meet this criterion. The present study investigates the PV prevalence in BRCA1, BRCA2, and nine additional cancer predisposition genes in an extended sTNBC study sample including a cohort of women with a later age at sTNBC diagnosis. Patients and Methods: In 1,600 women with sTNBC (median age at diagnosis: 41 years, range 19-78 years), we investigated the association between age at diagnosis and PV occurrence in cancer predisposition genes using logistic regression. Results: 260 sTNBC patients (16.2%) were found to have a PV in cancer predisposition genes (BRCA1: n = 170 [10.6%]; BRCA2: n = 46 [2.9%], other: n = 44 [2.8%]). The PV prevalence in women diagnosed between 50 and 59 years (n = 194) was 11.3% (22/194). Logistic regression showed a significant increase in PV prevalence with decreasing age at diagnosis (OR 1.41 per 10 years younger age at diagnosis; 95% confidence interval: 1.21-1.65; p < 0.001). The PV prevalence predicted by the model was above 10% for diagnoses before the age of 56.8 years. Conclusion: Based on the data presented, we recommend genetic testing by gene panel analysis for sTNBC patients diagnosed before the age of 60 years. Due to the still uncertain estimate for women with sTNBC diagnosed above the age of 60 years, further studies are needed.

Details

Original languageEnglish
Pages (from-to)106-112
Number of pages7
JournalBreast care
Volume18
Issue number2
Publication statusPublished - 1 Apr 2023
Peer-reviewedYes

Keywords

Sustainable Development Goals

ASJC Scopus subject areas

Keywords

  • BRCA1, BRCA2, triple negative, Breast cancer, Hereditary breast and ovarian cancer