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Frequency and spectrum of mutations across 94 cancer predisposition genes in African American women with invasive breast cancer


African American women are at increased risk of being diagnosed at a young age and/or with triple negative breast cancer, both factors which are included in current guidelines for identifying women who may benefit from genetic testing. Commercial breast cancer predisposition genetic panels, based largely on data derived from women of European ancestry, may not capture the full spectrum of cancer predisposition genes associated with breast cancer in African American women. Between 2001 and 2018, 488 unselected African American women with invasive breast cancer enrolled in the Clinical Breast Care Project. National Comprehensive Cancer Network (NCCN) Hereditary Cancer testing criteria version 1.2020 were applied to determine genetic risk. Targeted sequencing was performed using the TruSight Cancer panel and variants classified using the ClinVar database. Using NCCN criteria, 64.1% of African American women would be eligible for genetic testing. Fifty pathogenic or likely pathogenic mutations were detected in 19 genes with the highest frequencies in BRCA2 (29.4%) and BRCA1 (15.7%). Mutation frequencies in test-eligible and test-ineligible women were 13.1% and 3.5%, respectively. One-third of women harbored variants that could not be classified. While these data do not suggest a need to expand current commercial gene panels, NCCN criteria would fail to identify 12.5% of African American women with mutations in hereditary cancer predisposing genes.

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The contents of this publication are the sole responsibility of the author(s) and do not necessarily reflect the views, opinions or policies of Uniformed Services University of the Health Sciences (USUHS), The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., the Department of Defense (DoD) or the Departments of the Army, Navy, or Air Force. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. Government.


This research was supported by a cooperative agreement from the Uniformed Services University of the Health Sciences HU0001-16-2-0004 through the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.

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Study concept and design (REE); acquisition of data (LAL, SKR, CDS); analysis and interpretation of data (REE, CET); drafting of the manuscript (REE); critical revision of the manuscript for important intellectual content (LAL, SKR, CET, CDS).

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Correspondence to Rachel E. Ellsworth.

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The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

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Demographic and pathologic data and blood samples were collected with approval from the WRNMMC Human Use Committee and Institutional Review Board (protocol WRNMMC IRB #20704).

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All subjects voluntarily agreed to participate in the CBCP and gave written informed consent.

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Lovejoy, L.A., Rummel, S.K., Turner, C.E. et al. Frequency and spectrum of mutations across 94 cancer predisposition genes in African American women with invasive breast cancer. Familial Cancer 20, 181–187 (2021).

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