Real world data analysis of next generation sequencing and protein expression in metastatic breast cancer patients.
Adult
Aged
Aged, 80 and over
Breast Neoplasms
/ genetics
Class I Phosphatidylinositol 3-Kinases
/ genetics
Estrogen Receptor alpha
/ genetics
Female
Gene Expression Regulation, Neoplastic
/ genetics
High-Throughput Nucleotide Sequencing
Humans
Middle Aged
Mutation
/ genetics
Neoplasm Proteins
/ genetics
Receptor, ErbB-2
/ genetics
Receptor, Fibroblast Growth Factor, Type 1
/ genetics
Retrospective Studies
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
26 06 2020
26 06 2020
Historique:
received:
20
03
2020
accepted:
05
06
2020
entrez:
28
6
2020
pubmed:
28
6
2020
medline:
15
12
2020
Statut:
epublish
Résumé
Next generation sequencing (NGS) together with protein expression analysis is back bone of molecularly targeted therapy in precision medicine. Our retrospective study shows our experience with NGS of 324 genes in combination with protein expression in patients with advanced breast cancer (aBC). The primary purpose was to analyze the prevalence of individual genetic alterations combined with protein expression to define potential targets for an individualized therapy. Between April 2018 and September 2019, 41 patients with aBC were offered a NGS test. The test was used to detect clinically relevant genomic alterations and to support further targeted therapy decisions. Hormone receptors, ERBB2 of tumors and PD-L1 was stained by immunohistochemistry. The data was recorded up to September 2019. After prior consent 41 results were available for further analysis. The most common BC subtypes were triple-negative (n = 16), HR+/ERBB2- (n = 15), and ERBB2+ (n = 9), with one missing data of the primary tumor. 27 patients had more than one genetic alteration. The most common alterations were PIK3CA (n = 14) and ERBB2 alterations (n = 11). Followed by ESR1 (n = 10), FGFR1 (n = 7) and PTEN (n = 7). 68% of the alterations were clinically relevant (tier I and II of ESCAT classification). The most common treatment recommendation was ERBB2-directed therapy (single or double blockade, trastuzumab emtansine and lapatinib) followed by alpelisib in combination with fulvestrant. Comprehensive genomic profiling combined with protein expression analysis in aBC allowed a guided personalized therapy for half of our patients. So far there are no well-defined tools allowing interpretations of genomic alterations detected by NGS in combination with protein expression and other factors.
Identifiants
pubmed: 32591580
doi: 10.1038/s41598-020-67393-9
pii: 10.1038/s41598-020-67393-9
pmc: PMC7319999
doi:
Substances chimiques
ESR1 protein, human
0
Estrogen Receptor alpha
0
Neoplasm Proteins
0
Class I Phosphatidylinositol 3-Kinases
EC 2.7.1.137
PIK3CA protein, human
EC 2.7.1.137
ERBB2 protein, human
EC 2.7.10.1
FGFR1 protein, human
EC 2.7.10.1
Receptor, ErbB-2
EC 2.7.10.1
Receptor, Fibroblast Growth Factor, Type 1
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
10459Références
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