Exome sequencing reveals frequent deleterious germline variants in cancer susceptibility genes in women with invasive breast cancer undergoing neoadjuvant chemotherapyReportar como inadecuado




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Breast Cancer Research and Treatment

, Volume 153, Issue 2, pp 435–443

First Online: 22 August 2015Received: 08 August 2015Accepted: 10 August 2015DOI: 10.1007-s10549-015-3545-6

Cite this article as: Ellingson, M.S., Hart, S.N., Kalari, K.R. et al. Breast Cancer Res Treat 2015 153: 435. doi:10.1007-s10549-015-3545-6

Abstract

When sequencing blood and tumor samples to identify targetable somatic variants for cancer therapy, clinically relevant germline variants may be uncovered. We evaluated the prevalence of deleterious germline variants in cancer susceptibility genes in women with breast cancer referred for neoadjuvant chemotherapy and returned clinically actionable results to patients. Exome sequencing was performed on blood samples from women with invasive breast cancer referred for neoadjuvant chemotherapy. Germline variants within 142 hereditary cancer susceptibility genes were filtered and reviewed for pathogenicity. Return of results was offered to patients with deleterious variants in actionable genes if they were not aware of their result through clinical testing. 124 patients were enrolled median age 51 with the following subtypes: triple negative n = 43, 34.7 %, HER2+ n = 37, 29.8 %, luminal B n = 31, 25 %, and luminal A n = 13, 10.5 %. Twenty-eight deleterious variants were identified in 26-124 21.0 % patients in the following genes: ATM n = 3, BLM n = 1, BRCA1 n = 4, BRCA2 n = 8, CHEK2 n = 2, FANCA n = 1, FANCI n = 1, FANCL n = 1, FANCM n = 1, FH n = 1, MLH3 n = 1, MUTYH n = 2, PALB2 n = 1, and WRN n = 1. 121-124 97.6 % patients consented to return of research results. Thirteen 10.5 % had actionable variants, including four that were returned to patients and led to changes in medical management. Deleterious variants in cancer susceptibility genes are highly prevalent in patients with invasive breast cancer referred for neoadjuvant chemotherapy undergoing exome sequencing. Detection of these variants impacts medical management.

KeywordsBreast cancer Neoadjuvant chemotherapy High-risk breast cancer Return of results Exome sequencing Germline mutation-pathogenic germline variant Electronic supplementary materialThe online version of this article doi:10.1007-s10549-015-3545-6 contains supplementary material, which is available to authorized users.

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Fuente: https://link.springer.com/







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