scholarly journals Next-Generation Sequencing-Directed Therapy in Patients with Metastatic Breast Cancer in Routine Clinical Practice

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4564
Author(s):  
Simona Bruzas ◽  
Sherko Kuemmel ◽  
Hakima Harrach ◽  
Elisabeth Breit ◽  
Beyhan Ataseven ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Clinical Practice ◽  
Next Generation Sequencing ◽  
Standard Therapy ◽  
Metastatic Breast ◽  
Genetic Alterations ◽  
Tumor Board ◽  
Next Generation ◽  
Generation Sequencing

Next-generation sequencing (NGS) followed by matched therapy has opened up new therapeutic options to patients with metastatic breast cancer (mBC). Here we report our experience with this approach in everyday clinical practice. This retrospective study included 95 patients with mBC who were genotyped with the FoundationOne® (CDx) assay in a commercial molecular pathology laboratory. Genetic alterations were identified in all tumor specimens, and 83 patients (87.4%) had a median of 2 (range, 1–6) potentially actionable alterations. A multidisciplinary tumor board recommended genomically guided therapy to 63 patients, 30 of whom received such treatment. Everolimus (n = 15) and anti-human epidermal growth factor receptor 2 (HER2) therapy (n = 6) were most frequently administered. The ratio of progression-free survival (PFS) under NGS-based therapy to PFS under the last line of standard therapy prior to NGS was >1.3 in 13 (43.3%) patients, indicative of a clinical benefit to NGS-directed therapy. One-year overall survival rates were 22.7% (95% CI, 6.5–44.4) in 65 patients allocated to the standard therapy versus 62.9% (95% CI, 41.6–78.2) in 30 patients receiving the matched therapy. In conclusion, NGS-matched treatment improved the clinical outcomes in a subgroup of mBC patients.

scholarly journals Mutational analysis of single circulating tumor cells by next generation sequencing in metastatic breast cancer

Oncotarget ◽  
2016 ◽  
Vol 7 (18) ◽  
pp. 26107-26119 ◽  
Author(s):  
Francesca De Luca ◽  
Giada Rotunno ◽  
Francesca Salvianti ◽  
Francesca Galardi ◽  
Marta Pestrin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Next Generation Sequencing ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Mutational Analysis ◽  
Metastatic Breast ◽  
Next Generation ◽  
Generation Sequencing

scholarly journals Next Generation Sequencing of Circulating Cell-Free DNA for Evaluating Mutations and Gene Amplification in Metastatic Breast Cancer

2017 ◽  
Vol 63 (2) ◽  
pp. 532-541 ◽  
Author(s):  
Karen Page ◽  
David S Guttery ◽  
Daniel Fernandez-Garcia ◽  
Allison Hills ◽  
Robert K Hastings ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Next Generation Sequencing ◽  
Gene Amplification ◽  
Somatic Mutations ◽  
Metastatic Breast ◽  
Healthy Controls ◽  
Next Generation ◽  
Free Dna ◽  
Generation Sequencing

Abstract BACKGROUND Breast cancer tissues are heterogeneous and show diverse somatic mutations and somatic copy number alterations (CNAs). We used a novel targeted next generation sequencing (NGS) panel to examine cell-free DNA (cfDNA) to detect somatic mutations and gene amplification in women with metastatic breast cancer (MBC). METHODS cfDNA from pretreated patients (n = 42) and 9 healthy controls were compared with matched lymphocyte DNA by NGS, using a custom 158 amplicon panel covering hot-spot mutations and CNAs in 16 genes, with further validation of results by droplet digital PCR. RESULTS No mutations were identified in cfDNA of healthy controls, whereas exactly half the patients with metastatic breast cancer had at least one mutation or amplification in cfDNA (mean 2, range 1–6) across a total of 13 genes. Longitudinal follow up showed dynamic changes to mutations and gene amplification in cfDNA indicating clonal and subclonal response to treatment that was more dynamic than cancer antigen 15-3 (CA15-3). Interestingly, at the time of blood sampling disease progression was occurring in 7 patients with erb-b2 receptor tyrosine kinase 2 (ERBB2) gene amplification in their cfDNA and 3 of these patients were human epidermal growth factor receptor 2 (HER2) negative at diagnosis, suggesting clonal evolution to a more aggressive phenotype. Lastly, 6 patients harbored estrogen receptor 1 (ESR1) mutations in cfDNA, suggesting resistance to endocrine therapy. Overall 9 of 42 patients (21%) had alterations in cfDNA that could herald a change in treatment. CONCLUSIONS Targeted NGS of cfDNA has potential for monitoring response to targeted therapies through both mutations and gene amplification, for analysis of dynamic tumor heterogeneity and stratification to targeted therapy.

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