Prevalence of pathogenic germline variants in women with non-familial unilateral tri-ple-negative breast cancer

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 can-cer predisposition genes in an extended sTNBC study sample including a cohort of women with a later age at sTNBC diagnosis. Patients and methods: In 1600 women with sTNBC (median age at diagnosis 41 years, range 19-78 years) we investigated the association between age at diagnosis and PV occur-rence 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%CI 1.21-1.65; p <0.001). The PV prevalence pre-dicted 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 wide confi-dence interval (7.6-16-6), we recommend the implementation within the framework of a knowledge-generating care concept.