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.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
US Preventive ServicesTask Force, Owens DK, Davidson KW, Krist AH, Barry MJ, Cabana M, Caughey AB, Doubeni CA, Epling JW, Kubik M, Landefeld CS, Mangione CM, Pbert L, Silverstein M, Simon MA, Tseng CW, Wong JB (2019) Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer: US Preventive Services Task Force recommendation statement. JAMA 322(7):652–665. https://doi.org/10.1001/jama.2019.10987
National Comprehensive Cancer Network (NCCN) (2019) NCCN Guidelines version 1.2019 BRCA-related breast and/or ovarian cancer syndrome
National Comprehensive Cancer Network (NCCN) (2010) NCCN Guidelines version 1.2020 Hereditary testing criteria
Beitsch PD, Whitworth PW, Hughes K, Patel R, Rosen B, Compagnoni G, Baron P, Simmons R, Smith LA, Grady I, Kinney M, Coomer C, Barbosa K, Holmes, Brown E, Gold L, Clark P, Riley L, Lyons S, Ruiz A, Kahn S, MacDonald H, Curcio L, Hardwick MK, Yang S, Esplin ED, Nussbaum RL (2019) Underdiagnosis of hereditary breast cancer: are genetic testing guidelines a tool or an obstacle? J Clin Oncol 37(6):453–460. https://doi.org/10.1200/jco.18.01631
Buys SS, Sandbach JF, Gammon A, Patel G, Kidd J, Brown KL, Sharma L, Saam J, Lancaster J, Daly MB (2017) A study of over 35,000 women with breast cancer tested with a 25-gene panel of hereditary cancer genes. Cancer 123(10):1721–1730. https://doi.org/10.1002/cncr.30498
Tung N, Lin NU, Kidd J, Allen BA, Singh N, Wenstrup RJ, Hartman AR, Winer EP, Garber JE (2016) Frequency of germline mutations in 25 cancer susceptibility genes in a sequential series of patients with breast cance. J Clin Oncol 34(13):1460–1468. https://doi.org/10.1200/jco.2015.65.0747
Hammond MEH, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, Hicks DG, Lester S, Love R, Mangu PB, McShane L, Miller K, Osborne CK, Paik S, Perlmutter J, Rhodes A, Sasano H, Schwartz JN, Sweep FCG, Taube S, Torlakovic EE, Valenstein P, Viale G, Visscher D, Wheeler T, Williams RB, Wittliff JL, Wolff AC (2010) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol 28(16):2784–2795
Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, Allred DC, Bartlett JM, Bilous M, Fitzgibbons P, Hanna W, Jenkins RB, Mangu PB, Paik S, Perez EA, Press MF, Spears PA, Vance GH, Viale G, Hayes DF, American Society of Clinical O, College of American P (2013) Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American pathologists clinical practice guideline update. J Clin Oncol 31(31):3997–4013. https://doi.org/10.1200/jco.2013.50.9984
Cragun D, Weidner A, Lewis C, Bonner D, Kim J, Vadaparampil ST, Pal T (2017) Racial disparities in BRCA testing and cancer risk management across a population-based sample of young breast cancer survivors. Cancer 123(13):2497–2505. https://doi.org/10.1002/cncr.30621
Levy DE, Byfield SD, Comstock CB, Garber JE, Syngal S, Crown WH, Shields AE (2011) Underutilization of BRCA1/2 testing to guide breast cancer treatment: black and hispanic women particularly at risk. Genet Med 13(4):349–355. https://doi.org/10.1097/gim.0b013e3182091ba4
Pal T, Bonner D, Cragun D, Monteiro AN, Phelan C, Servais L, Kim J, Narod SA, Akbari MR, Vadaparampil ST (2015) A high frequency of BRCA mutations in young black women with breast cancer residing in Florida. Cancer 121(23):4173–4180. https://doi.org/10.1002/cncr.29645
Ricks-Santi L, McDonald JT, Gold B, Dean M, Thompson N, Abbas M, Wilson B, Kanaan Y, Naab TJ, Dunston G (2017) Next generation sequencing reveals high prevalence of BRCA1 and BRCA2 variants of unknown significance in early-onset breast cancer in African American women. Ethn Dis 27(2):169–178. https://doi.org/10.18865/ed.27.2.169
Shimelis H, LaDuca H, Hu C, Hart SN, Na J, Thomas A, Akinhanmi M, Moore RM, Brauch H, Cox A, Eccles DM, Ewart-Toland A, Fasching PA, Fostira F, Garber J, Godwin AK, Konstantopoulou I, Nevanlinna H, Sharma P, Yannoukakos D, Yao S, Feng BJ, Tippin Davis B, Lilyquist J, Pesaran T, Goldgar DE, Polley EC, Dolinsky JS, Couch FJ (2018) Triple-negative breast cancer risk genes identified by multigene hereditary cancer panel testing. J Natl Cancer Inst 110(8):855–862. https://doi.org/10.1093/jnci/djy106
Churpek JE, Walsh T, Zheng Y, Moton Z, Thornton AM, Lee MK, Casadei S, Watts A, Neistadt B, Churpek MM, Huo D, Zvosec C, Liu F, Niu Q, Marquez R, Zhang J, Fackenthal J, King MC, Olopade OI (2015) Inherited predisposition to breast cancer among African American women. Breast Cancer Res Treat 149(1):31–39. https://doi.org/10.1007/s10549-014-3195-0
Ademuyiwa FO, Salyer P, Ma Y, Fisher S, Colditz G, Weilbaecher K, Bierut LJ (2019) Assessing the effectiveness of the National Comprehensive Cancer Network genetic testing guidelines in identifying African American breast cancer patients with deleterious genetic mutations. Breast Cancer Res Treat 178(1):151–159. https://doi.org/10.1007/s10549-019-05359-w
Couch FJ, Shimelis H, Hu C, Hart SN, Polley EC, Na J, Hallberg E, Moore R, Thomas A, Lilyquist J, Feng B, McFarland R, Pesaran T, Huether R, LaDuca H, Chao EC, Goldgar DE, Dolinsky JS (2017) Associations between cancer predisposition testing panel genes and breast cancer. JAMA Oncol 3(9):1190–1196. https://doi.org/10.1001/jamaoncol.2017.0424
Mersha TB, Abebe T (2015) Self-reported race/ethnicity in the age of genomic research: its potential impact on understanding health disparities. Hum Genomics 9:1. https://doi.org/10.1186/s40246-014-0023-x
Adeloye D, Sowunmi OY, Jacobs W, David RA, Adeosun AA, Amuta AO, Misra S, Gadanya M, Auta A, Harhay MO, Chan KY (2018) Estimating the incidence of breast cancer in Africa: a systematic review and meta-analysis. J Glob Health 8(1):010419. https://doi.org/10.7189/jogh.08.010419
Jiagge E, Jibril AS, Chitale D, Bensenhaver JM, Awuah B, Hoenerhoff M, Adjei E, Bekele M, Abebe E, Nathanson SD, Gyan K, Salem B, Oppong J, Aitpillah F, Kyei I, Bonsu EO, Proctor E, Merajver SD, Wicha M, Stark A, Newman LA (2016) Comparative analysis of breast cancer phenotypes in African American, White American, and West versus East African patients: correlation between African ancestry and triple-negative breast cancer. Ann Surg Oncol 23(12):3843–3849. https://doi.org/10.1245/s10434-016-5420-z
Ssentongo P, Lewcun JA, Candela X, Ssentongo AE, Kwon EG, Ba DM, Oh JS, Amponsah-Manu F, McDonald AC, Chinchilli VM, Soybel DI, Dodge DG (2019) Regional, racial, gender, and tumor biology disparities in breast cancer survival rates in Africa: a systematic review and meta-analysis. PLoS ONE 14(11):e0225039. https://doi.org/10.1371/journal.pone.0225039
del Valle J, Feliubadalo L, Nadal M, Teule A, Miro R, Cuesta R, Tornero E, Menendez M, Darder E, Brunet J, Capella G, Blanco I, Lazaro C (2010) Identification and comprehensive characterization of large genomic rearrangements in the BRCA1 and BRCA2 genes. Breast Cancer Res Treat 122(3):733–743. https://doi.org/10.1007/s10549-009-0613-9
Manahan ER, Kuerer HM, Sebastian M, Hughes KS, Boughey JC, Euhus DM, Boolbol SK, Taylor WA (2019) Consensus guidelines on genetic` testing for hereditary breast cancer from the american society of breast surgeons. Ann Surg Oncol 26(10):3025–3031. https://doi.org/10.1245/s10434-019-07549-8
National Comprehensive Cancer Network (2019) Genetic/familial high-risk assessment: breast and ovarian cancer 2.2017, vol 3.2019
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.
Conflicts of interest
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.
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).
All subjects voluntarily agreed to participate in the CBCP and gave written informed consent.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
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). https://doi.org/10.1007/s10689-020-00213-1