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Open Access 01-01-2015 | Preclinical study

Inherited predisposition to breast cancer among African American women

Authors: Jane E. Churpek, Tom Walsh, Yonglan Zheng, Zakiya Moton, Anne M. Thornton, Ming K. Lee, Silvia Casadei, Amanda Watts, Barbara Neistadt, Matthew M. Churpek, Dezheng Huo, Cecilia Zvosec, Fang Liu, Qun Niu, Rafael Marquez, Jing Zhang, James Fackenthal, Mary-Claire King, Olufunmilayo I. Olopade

Published in: Breast Cancer Research and Treatment | Issue 1/2015

Abstract

African Americans have a disproportionate burden of aggressive young-onset breast cancer. Genomic testing for inherited predisposition to breast cancer is increasingly common in clinical practice, but comprehensive mutation profiles remain unknown for most minority populations. We evaluated 289 patients who self-identified as African American with primary invasive breast cancer and with personal or family cancer history or tumor characteristics associated with high genetic risk for all classes of germline mutations in known breast cancer susceptibility genes using a validated targeted capture and multiplex sequencing approach. Sixty-eight damaging germline mutations were identified in 65 (22 %, 95 % CI 18–28 %) of the 289 subjects. Proportions of patients with unequivocally damaging mutations in a breast cancer gene were 26 % (47/180; 95 % confident interval [CI] 20–33 %) of those with breast cancer diagnosis before age 45; 25 % (26/103; 95 % CI 17–35 %) of those with triple-negative breast cancer (TNBC); 29 % (45/156; 95 % CI 22–37 %) of those with a first or second degree relative with breast cancer before age 60 or with ovarian cancer; and 57 % (4/7; 95 % CI 18–90 %) of those with both breast and ovarian cancer. Of patients with mutations, 80 % (52/65) carried mutations in BRCA1 and BRCA2 genes and 20 % (13/65) carried mutations in PALB2, CHEK2, BARD1, ATM, PTEN, or TP53. The mutational allelic spectrum was highly heterogeneous, with 57 different mutations in 65 patients. Of patients meeting selection criteria other than family history (i.e., with young age at diagnosis or TNBC), 48 % (64/133) had very limited information about the history of cancer in previous generations of their families. Mutations in BRCA1 and BRCA2 or another breast cancer gene occur in one in four African American breast cancer patients with early onset disease, family history of breast or ovarian cancer, or TNBC. Each of these criteria defines patients who would benefit from genomic testing and novel therapies targeting DNA repair pathways.

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Title: Inherited predisposition to breast cancer among African American women
Authors: Jane E. Churpek
Tom Walsh
Yonglan Zheng
Zakiya Moton
Anne M. Thornton
Ming K. Lee
Silvia Casadei
Amanda Watts
Barbara Neistadt
Matthew M. Churpek
Dezheng Huo
Cecilia Zvosec
Fang Liu
Qun Niu
Rafael Marquez
Jing Zhang
James Fackenthal
Mary-Claire King
Olufunmilayo I. Olopade
Publication date: 01-01-2015
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 1/2015
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-014-3195-0

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