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

Breast care

article

Rhiem, Kerstin¹  Zachariae, Silke²  Waha, Anke¹  Grill, Sabine³  Hester, Anna⁴  Golatta, Michael⁵  van Mackelenbergh, Marion⁶  Fehm, Tanja⁷  Schlaiß, Tanja⁸  Ripperger, Tim⁹  Ledig, Susanne^1,10  Meisel, Cornelia^1,11  Speiser, Dorothee^1,15  Veselinovic, Kristina^1,16  Schröder, Christopher^1,17  Witzel, Isabell^1,18  Gallwas, Julia^1,19  Weber, Bernhard H.F.^2,20  Solbach, Christine^2,22  Aktas, Bariyhe^2,23  Hahnen, Eric¹  Engel, Christoph²  Schmutzler, Rita¹ 

[1]Center for Hereditary Breast and Ovarian Cancer and Center for Integrated Oncology ,(CIO), Medical Faculty, University Hospital Cologne

[2]Institute for Medical Informatics, Statistics and Epidemiology, Leipzig University

[3]Department of Gynecology and Center for Hereditary Breast and Ovarian Cancer, Klinikum Rechts der Isar, Technical University Munich

[4]Department of Obstetrics and Gynecology, University Hospital, Ludwig-Maximilians-University

[5]Department of Gynecology and Obstetrics, University of Heidelberg

[6]Department Gynecology and Obstetrics, University Hospital Schleswig Holstein ,(UKSH) Campus Kiel

[7]Department of Gynecology and Obstetrics, University Hospital Düsseldorf

[8]Institute for Gynecology and Obstetrics and Center for Hereditary Breast and Ovarian Can-cer, Medical Faculty, University Hospital Würzburg

[9]Department of Human Genetics, Hannover Medical School

[10]Institute of Human Genetics, University of Münster

[11]Department of Gynecology and Obstetrics, Technische Universität Dresden

[12]National Center for Tumor Diseases ,(NCT/UCC), Dresden, Germany: German Cancer Research Center

[13]Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden

[14]Helmholtz-Centre Dresden - Rossendorf

[15]Department of Gynecology and Breast Centre, Centre for Hereditary Breast and Ovarian Cancer Charité, Charité University Hospital

[16]Department of Gynecology and Obstetrics, University Hospital Ulm

[17]Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen

[18]Department of Gynecology, University Hospital Hamburg-Eppendorf

[19]Department of Gynecology and Obstetrics, University Medicine Göttingen

[20]Institute of Human Genetics, University of Regensburg

[21]Institute of Clinical Human Genetics, University Hospital Regensburg

[22]Center for Hereditary Breast and Ovarian Cancer, University Hospital Frankfurt

[23]Department of Gynecology, University of Leipzig Medical Center

关键词: BRCA1;    BRCA2;    triple negative;    Breast cancer;    Hereditary breast and ovarian cancer;   

DOI  :  10.1159/000528972

学科分类：泌尿医学

来源: S Karger AG

【 摘 要 】

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.

【 授权许可】

CC BY