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Multiple gene aberrations and breast cancer: lessons from super-responders
BACKGROUND: The presence of multiple molecular aberrations in patients with breast cancer may correlate with worse outcomes. CASE PRESENTATIONS: We performed in-depth molecular analysis of patients with estrogen receptor-positive, HER2-negative, hormone therapy-refractory breast cancer, who achieved...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4446801/ https://www.ncbi.nlm.nih.gov/pubmed/26021831 http://dx.doi.org/10.1186/s12885-015-1439-y |
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author | Wheler, Jennifer J. Atkins, Johnique T. Janku, Filip Moulder, Stacy L. Yelensky, Roman Stephens, Philip J. Kurzrock, Razelle |
author_facet | Wheler, Jennifer J. Atkins, Johnique T. Janku, Filip Moulder, Stacy L. Yelensky, Roman Stephens, Philip J. Kurzrock, Razelle |
author_sort | Wheler, Jennifer J. |
collection | PubMed |
description | BACKGROUND: The presence of multiple molecular aberrations in patients with breast cancer may correlate with worse outcomes. CASE PRESENTATIONS: We performed in-depth molecular analysis of patients with estrogen receptor-positive, HER2-negative, hormone therapy-refractory breast cancer, who achieved partial or complete responses when treated with anastrozole and everolimus. Tumors were analyzed using a targeted next generation sequencing (NGS) assay in a Clinical Laboratory Improvement Amendments laboratory. Genomic libraries were captured for 3,230 exons in 182 cancer-related genes plus 37 introns from 14 genes often rearranged in cancer and sequenced to high coverage. Patients received anastrozole (1 mg PO daily) and everolimus (5 or 10 mg PO daily). Thirty-two patients with breast cancer were treated on study and 5 (16 %) achieved a partial or complete response. Primary breast tissue was available for NGS testing in three of the responders (partial response with progression free survival of 11 and 14 months, respectively; complete response with progression free survival of 9+ months). The following molecular aberrations were observed: PTEN loss by immunohistochemistry, CCDN1 and FGFR1 amplifications, and PRKDC re-arrangement (NGS) (patient #1); PIK3CA and PIK3R1 mutations, and CCDN1, FGFR1, MYC amplifications (patient #2); TP53 mutation, CCNE1, IRS2 and MCL1 amplifications (patient #3). Some (but not all) of these aberrations converge on the PI3K/AKT/mTOR pathway, perhaps accounting for response. CONCLUSIONS: Patients with estrogen receptor-positive breast cancer can achieve significant responses on a combination of anastrozole and everolimus, even in the presence of multiple molecular aberrations. Further study of next generation sequencing-profiled tumors for convergence and resistance pathways is warranted. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1439-y) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4446801 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-44468012015-05-29 Multiple gene aberrations and breast cancer: lessons from super-responders Wheler, Jennifer J. Atkins, Johnique T. Janku, Filip Moulder, Stacy L. Yelensky, Roman Stephens, Philip J. Kurzrock, Razelle BMC Cancer Case Report BACKGROUND: The presence of multiple molecular aberrations in patients with breast cancer may correlate with worse outcomes. CASE PRESENTATIONS: We performed in-depth molecular analysis of patients with estrogen receptor-positive, HER2-negative, hormone therapy-refractory breast cancer, who achieved partial or complete responses when treated with anastrozole and everolimus. Tumors were analyzed using a targeted next generation sequencing (NGS) assay in a Clinical Laboratory Improvement Amendments laboratory. Genomic libraries were captured for 3,230 exons in 182 cancer-related genes plus 37 introns from 14 genes often rearranged in cancer and sequenced to high coverage. Patients received anastrozole (1 mg PO daily) and everolimus (5 or 10 mg PO daily). Thirty-two patients with breast cancer were treated on study and 5 (16 %) achieved a partial or complete response. Primary breast tissue was available for NGS testing in three of the responders (partial response with progression free survival of 11 and 14 months, respectively; complete response with progression free survival of 9+ months). The following molecular aberrations were observed: PTEN loss by immunohistochemistry, CCDN1 and FGFR1 amplifications, and PRKDC re-arrangement (NGS) (patient #1); PIK3CA and PIK3R1 mutations, and CCDN1, FGFR1, MYC amplifications (patient #2); TP53 mutation, CCNE1, IRS2 and MCL1 amplifications (patient #3). Some (but not all) of these aberrations converge on the PI3K/AKT/mTOR pathway, perhaps accounting for response. CONCLUSIONS: Patients with estrogen receptor-positive breast cancer can achieve significant responses on a combination of anastrozole and everolimus, even in the presence of multiple molecular aberrations. Further study of next generation sequencing-profiled tumors for convergence and resistance pathways is warranted. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1439-y) contains supplementary material, which is available to authorized users. BioMed Central 2015-05-29 /pmc/articles/PMC4446801/ /pubmed/26021831 http://dx.doi.org/10.1186/s12885-015-1439-y Text en © Wheler et al.; licensee BioMed Central. 2015 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Case Report Wheler, Jennifer J. Atkins, Johnique T. Janku, Filip Moulder, Stacy L. Yelensky, Roman Stephens, Philip J. Kurzrock, Razelle Multiple gene aberrations and breast cancer: lessons from super-responders |
title | Multiple gene aberrations and breast cancer: lessons from super-responders |
title_full | Multiple gene aberrations and breast cancer: lessons from super-responders |
title_fullStr | Multiple gene aberrations and breast cancer: lessons from super-responders |
title_full_unstemmed | Multiple gene aberrations and breast cancer: lessons from super-responders |
title_short | Multiple gene aberrations and breast cancer: lessons from super-responders |
title_sort | multiple gene aberrations and breast cancer: lessons from super-responders |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4446801/ https://www.ncbi.nlm.nih.gov/pubmed/26021831 http://dx.doi.org/10.1186/s12885-015-1439-y |
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