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Breast Cancer Research
Published in: Breast Cancer Research 1/2020

Open Access 01-12-2020 | Breast Cancer | Research article

Clinical implications of prospective genomic profiling of metastatic breast cancer patients

Authors: Courtney T. van Geelen, Peter Savas, Zhi Ling Teo, Stephen J. Luen, Chen-Fang Weng, Yi-An Ko, Keilly S. Kuykhoven, Franco Caramia, Roberto Salgado, Prudence A. Francis, Sarah-Jane Dawson, Stephen B. Fox, Andrew Fellowes, Sherene Loi

Published in: Breast Cancer Research | Issue 1/2020

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Abstract

Background

Metastatic breast cancer remains incurable. Next-generation sequencing (NGS) offers the ability to identify actionable genomic alterations in tumours which may then be matched with targeted therapies, but the implementation and utility of this approach is not well defined for patients with metastatic breast cancer.

Methods

We recruited patients with advanced breast cancer of any subtype for prospective targeted NGS of their most recent tumour samples, using a panel of 108 breast cancer-specific genes. Genes were classified as actionable or non-actionable using the European Society of Medical Oncology Scale for Clinical Actionability of Molecular Targets (ESCAT) guidelines.

Results

Between February 2014 and May 2019, 322 patients were enrolled onto the study, with 72% (n = 234) of patients successfully sequenced (n = 357 samples). The majority (74%, n = 171) of sequenced patients were found to carry a potentially actionable alteration, the most common being a PIK3CA mutation. Forty-three percent (n = 74) of patients with actionable alterations were referred for a clinical trial or referred for confirmatory germline testing or had a change in therapy outside of clinical trials. We found alterations in AKT1, BRCA2, CHEK2, ESR1, FGFR1, KMT2C, NCOR1, PIK3CA and TSC2 to be significantly enriched in our metastatic population compared with primary breast cancers. Concordance between primary and metastatic samples for key driver genes (TP53, ERBB2 amplification) was > 75%. Additionally, we found that patients with a higher number of mutations had a significantly worse overall survival.

Conclusion

Genomic profiling of patients with metastatic breast cancer can have clinical implications and should be considered in all suitable patients.
Appendix
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Metadata
Title
Clinical implications of prospective genomic profiling of metastatic breast cancer patients
Authors
Courtney T. van Geelen
Peter Savas
Zhi Ling Teo
Stephen J. Luen
Chen-Fang Weng
Yi-An Ko
Keilly S. Kuykhoven
Franco Caramia
Roberto Salgado
Prudence A. Francis
Sarah-Jane Dawson
Stephen B. Fox
Andrew Fellowes
Sherene Loi
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2020
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-020-01328-0

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