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. 2023 May;18(2):106-112.
doi: 10.1159/000528972. Epub 2023 Jan 6.

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

Kerstin Rhiem  1 , Silke Zachariae  2 , Anke Waha  1 , Sabine Grill  3 , Anna Hester  4 , Michael Golatta  5 , Marion van Mackelenbergh  6 , Tanja Fehm  7 , Tanja Schlaiß  8 , Tim Ripperger  9 , Susanne Ledig  10 , Cornelia Meisel  11   12   13   14 , Dorothee Speiser  15 , Kristina Veselinovic  16 , Christopher Schröder  17 , Isabell Witzel  18 , Julia Gallwas  19 , Bernhard H F Weber  20   21 , Christine Solbach  22 , Bariyhe Aktas  23 , Eric Hahnen  1 , Christoph Engel  2 , Rita Schmutzler  1
Affiliations

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

Kerstin Rhiem et al. Breast Care (Basel). 2023 May.

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.

Keywords: BRCA1; BRCA2, triple negative; Breast cancer; Hereditary breast and ovarian cancer.

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Conflict of interest statement

Christopher Schröder reports an institutional grant from Illumina and research grants from BMS Stiftung Immunonkologie outside the submitted work. Julia Gallwas is a member of the academic advisory board of the Bundesaerztekammer and was paid for lectures for Merck Sharp & Dohme and Roche Diagnostics between 2017 and 2019. All other authors have no conflicts to declare.

Figures

Fig. 1
Fig. 1
Association between age at sTNBC diagnosis and the prevalence of a pathogenic germline variant (PV) in BRCA1/2 and the other core genes. The bars show the PV prevalence for BRCA1 (red), BRCA2 (blue), and the other core genes (green), and the error bars show the 95% confidence intervals for the PV prevalence in BRCA1/2 and the other core genes (combined) in the individual age groups. The middle curve shows the PV prevalence predicted by the logistic regression model (with the 95% confidence interval as dashed curves). The dashed horizontal line (red) indicates the prevalence level of 10%, above which molecular genetic testing is recommended.
Fig. 2
Fig. 2
Association between age at sTNBC diagnosis and the predicted prevalence of a pathogenic germline variant (PV) in BRCA1/2 and the other core genes, assuming a complete screening of all core genes and the age dependence of the PV prevalence. The bars show the PV prevalence for BRCA1 (observed: red), BRCA2 (observed: blue), and the other core genes (observed: green, additional predicted prevalence: light green), and the error bars show the 95% confidence interval for the predicted PV prevalence in BRCA1/2 and the other core genes in the individual age groups. The dashed horizontal line indicates the prevalence of 10% above which molecular genetic testing is recommended.
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References

    1. Bilani N, Zabor EC, Elson L, Elimimian EB, Nahleh Z. Breast cancer in the United States a cross-sectional overview. J Cancer Epidemiol. 2020;2020:6387378. - PMC - PubMed
    1. Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast cancer. N Engl J Med. 2010;363((20)):1938–1948. - PubMed
    1. Metcalfe K, Lubinski J, Lynch HT, Ghadirian P, Foulkes WD, Kim-Sing C, et al. Family history of cancer and cancer risks in women with BRCA1 or BRCA2 mutations. J Natl Cancer Inst. 2010;102((24)):1874–1878. - PubMed
    1. Armstrong N, Ryder S, Forbes C, Ross J, Quek RG. A systematic review of the international prevalence of BRCA mutation in breast cancer. Clin Epidemiol. 2019;11:543–561. - PMC - PubMed
    1. Copson ER, Maishman TC, Tapper WJ, Cutress RI, Greville-Heygate S, Altman DG, et al. Germline BRCA mutation and outcome in young-onset breast cancer (POSH) a prospective cohort study. Lancet Oncol. 2018 Feb;19((2)):169–180. - PMC - PubMed