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Old 10-10-2020, 04:35 PM   #1
Nguyen
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Join Date: Nov 2005
Posts: 274
Clinical implications of prospectivegenomic profiling of metastatic breastcancer pati

https://breast-cancer-research.biome...58-020-01328-0


Clinical implications of prospective genomic profiling of metastatic breast cancer patients

Sherene Loi
47-60 minutes

Research article
Open Access
Published: 18 August 2020

Breast Cancer Research volume 22, Article number: 91 (2020) Cite this article

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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.
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