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Multi-gene panel testing for hereditary cancer predisposition in unsolved high-risk breast and ovarian cancer patients
PURPOSE: Many women with an elevated risk of hereditary breast and ovarian cancer have previously tested negative for pathogenic mutations in BRCA1 and BRCA2. Among them, a subset has hereditary susceptibility to cancer and requires further testing. We sought to identify specific groups who remain a...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410210/ https://www.ncbi.nlm.nih.gov/pubmed/28281021 http://dx.doi.org/10.1007/s10549-017-4181-0 |
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author | Crawford, Beth Adams, Sophie B. Sittler, Taylor van den Akker, Jeroen Chan, Salina Leitner, Ofri Ryan, Lauren Gil, Elad van ’t Veer, Laura |
author_facet | Crawford, Beth Adams, Sophie B. Sittler, Taylor van den Akker, Jeroen Chan, Salina Leitner, Ofri Ryan, Lauren Gil, Elad van ’t Veer, Laura |
author_sort | Crawford, Beth |
collection | PubMed |
description | PURPOSE: Many women with an elevated risk of hereditary breast and ovarian cancer have previously tested negative for pathogenic mutations in BRCA1 and BRCA2. Among them, a subset has hereditary susceptibility to cancer and requires further testing. We sought to identify specific groups who remain at high risk and evaluate whether they should be offered multi-gene panel testing. METHODS: We tested 300 women on a multi-gene panel who were previously enrolled in a long-term study at UCSF. As part of their long-term care, all previously tested negative for mutations in BRCA1 and BRCA2 either by limited or comprehensive sequencing. Additionally, they met one of the following criteria: (i) personal history of bilateral breast cancer, (ii) personal history of breast cancer and a first or second degree relative with ovarian cancer, and (iii) personal history of ovarian, fallopian tube, or peritoneal carcinoma. RESULTS: Across the three groups, 26 women (9%) had a total of 28 pathogenic mutations associated with hereditary cancer susceptibility, and 23 women (8%) had mutations in genes other than BRCA1 and BRCA2. Ashkenazi Jewish and Hispanic women had elevated pathogenic mutation rates. In addition, two women harbored pathogenic mutations in more than one hereditary predisposition gene. CONCLUSIONS: Among women at high risk of breast and ovarian cancer who have previously tested negative for pathogenic BRCA1 and BRCA2 mutations, we identified three groups of women who should be considered for subsequent multi-gene panel testing. The identification of women with multiple pathogenic mutations has important implications for family testing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10549-017-4181-0) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5410210 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-54102102017-05-15 Multi-gene panel testing for hereditary cancer predisposition in unsolved high-risk breast and ovarian cancer patients Crawford, Beth Adams, Sophie B. Sittler, Taylor van den Akker, Jeroen Chan, Salina Leitner, Ofri Ryan, Lauren Gil, Elad van ’t Veer, Laura Breast Cancer Res Treat Brief Report PURPOSE: Many women with an elevated risk of hereditary breast and ovarian cancer have previously tested negative for pathogenic mutations in BRCA1 and BRCA2. Among them, a subset has hereditary susceptibility to cancer and requires further testing. We sought to identify specific groups who remain at high risk and evaluate whether they should be offered multi-gene panel testing. METHODS: We tested 300 women on a multi-gene panel who were previously enrolled in a long-term study at UCSF. As part of their long-term care, all previously tested negative for mutations in BRCA1 and BRCA2 either by limited or comprehensive sequencing. Additionally, they met one of the following criteria: (i) personal history of bilateral breast cancer, (ii) personal history of breast cancer and a first or second degree relative with ovarian cancer, and (iii) personal history of ovarian, fallopian tube, or peritoneal carcinoma. RESULTS: Across the three groups, 26 women (9%) had a total of 28 pathogenic mutations associated with hereditary cancer susceptibility, and 23 women (8%) had mutations in genes other than BRCA1 and BRCA2. Ashkenazi Jewish and Hispanic women had elevated pathogenic mutation rates. In addition, two women harbored pathogenic mutations in more than one hereditary predisposition gene. CONCLUSIONS: Among women at high risk of breast and ovarian cancer who have previously tested negative for pathogenic BRCA1 and BRCA2 mutations, we identified three groups of women who should be considered for subsequent multi-gene panel testing. The identification of women with multiple pathogenic mutations has important implications for family testing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10549-017-4181-0) contains supplementary material, which is available to authorized users. Springer US 2017-03-09 2017 /pmc/articles/PMC5410210/ /pubmed/28281021 http://dx.doi.org/10.1007/s10549-017-4181-0 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Brief Report Crawford, Beth Adams, Sophie B. Sittler, Taylor van den Akker, Jeroen Chan, Salina Leitner, Ofri Ryan, Lauren Gil, Elad van ’t Veer, Laura Multi-gene panel testing for hereditary cancer predisposition in unsolved high-risk breast and ovarian cancer patients |
title | Multi-gene panel testing for hereditary cancer predisposition in unsolved high-risk breast and ovarian cancer patients |
title_full | Multi-gene panel testing for hereditary cancer predisposition in unsolved high-risk breast and ovarian cancer patients |
title_fullStr | Multi-gene panel testing for hereditary cancer predisposition in unsolved high-risk breast and ovarian cancer patients |
title_full_unstemmed | Multi-gene panel testing for hereditary cancer predisposition in unsolved high-risk breast and ovarian cancer patients |
title_short | Multi-gene panel testing for hereditary cancer predisposition in unsolved high-risk breast and ovarian cancer patients |
title_sort | multi-gene panel testing for hereditary cancer predisposition in unsolved high-risk breast and ovarian cancer patients |
topic | Brief Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410210/ https://www.ncbi.nlm.nih.gov/pubmed/28281021 http://dx.doi.org/10.1007/s10549-017-4181-0 |
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