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Inherited predisposition to breast cancer among African American women
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 pati...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4298662/ https://www.ncbi.nlm.nih.gov/pubmed/25428789 http://dx.doi.org/10.1007/s10549-014-3195-0 |
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author | Churpek, Jane E. Walsh, Tom Zheng, Yonglan Moton, Zakiya Thornton, Anne M. Lee, Ming K. Casadei, Silvia Watts, Amanda Neistadt, Barbara Churpek, Matthew M. Huo, Dezheng Zvosec, Cecilia Liu, Fang Niu, Qun Marquez, Rafael Zhang, Jing Fackenthal, James King, Mary-Claire Olopade, Olufunmilayo I. |
author_facet | Churpek, Jane E. Walsh, Tom Zheng, Yonglan Moton, Zakiya Thornton, Anne M. Lee, Ming K. Casadei, Silvia Watts, Amanda Neistadt, Barbara Churpek, Matthew M. Huo, Dezheng Zvosec, Cecilia Liu, Fang Niu, Qun Marquez, Rafael Zhang, Jing Fackenthal, James King, Mary-Claire Olopade, Olufunmilayo I. |
author_sort | Churpek, Jane E. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4298662 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-42986622015-01-23 Inherited predisposition to breast cancer among African American women Churpek, Jane E. Walsh, Tom Zheng, Yonglan Moton, Zakiya Thornton, Anne M. Lee, Ming K. Casadei, Silvia Watts, Amanda Neistadt, Barbara Churpek, Matthew M. Huo, Dezheng Zvosec, Cecilia Liu, Fang Niu, Qun Marquez, Rafael Zhang, Jing Fackenthal, James King, Mary-Claire Olopade, Olufunmilayo I. Breast Cancer Res Treat Preclinical Study 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. Springer US 2014-11-27 2015 /pmc/articles/PMC4298662/ /pubmed/25428789 http://dx.doi.org/10.1007/s10549-014-3195-0 Text en © The Author(s) 2014 https://creativecommons.org/licenses/by-nc/4.0/ Open AccessThis article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. |
spellingShingle | Preclinical Study Churpek, Jane E. Walsh, Tom Zheng, Yonglan Moton, Zakiya Thornton, Anne M. Lee, Ming K. Casadei, Silvia Watts, Amanda Neistadt, Barbara Churpek, Matthew M. Huo, Dezheng Zvosec, Cecilia Liu, Fang Niu, Qun Marquez, Rafael Zhang, Jing Fackenthal, James King, Mary-Claire Olopade, Olufunmilayo I. Inherited predisposition to breast cancer among African American women |
title | Inherited predisposition to breast cancer among African American women |
title_full | Inherited predisposition to breast cancer among African American women |
title_fullStr | Inherited predisposition to breast cancer among African American women |
title_full_unstemmed | Inherited predisposition to breast cancer among African American women |
title_short | Inherited predisposition to breast cancer among African American women |
title_sort | inherited predisposition to breast cancer among african american women |
topic | Preclinical Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4298662/ https://www.ncbi.nlm.nih.gov/pubmed/25428789 http://dx.doi.org/10.1007/s10549-014-3195-0 |
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