Page, Karen, Martinson, Luke J, Fernandez-Garcia, Daniel, Hills, Allison, Gleason, Kelly LT, Gray, Molly C, Rushton, Amelia J, Nteliopoulos, Georgios, Hastings, Robert K, Goddard, Kate et al (show 10 more authors)
(2021)
Circulating Tumor DNA Profiling From Breast Cancer Screening Through to Metastatic Disease.
JCO PRECISION ONCOLOGY, 5 (5).
pp. 1768-1776.
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Abstract
<h4>Purpose</h4>We investigated the utility of the Oncomine Breast cfDNA Assay for detecting circulating tumor DNA (ctDNA) in women from a breast screening population, including healthy women with no abnormality detected by mammogram, and women on follow-up through to advanced breast cancer.<h4>Materials and methods</h4>Blood samples were taken from 373 women (127 healthy controls recruited through breast screening, 28 ductal carcinoma in situ, 60 primary breast cancers, 47 primary breast cancer on follow-up, and 111 metastatic breast cancers [MBC]) to recover plasma and germline DNA for analysis with the Oncomine Breast cfDNA Assay on the Ion S5 platform.<h4>Results</h4>One hundred sixteen of 373 plasma samples had one or more somatic variants detected across eight of the 10 genes and were called ctDNA-positive; MBC had the highest proportion of ctDNA-positive samples (61; 55%) and healthy controls the lowest (20; 15.7%). <i>ESR1</i>, <i>TP53</i>, and <i>PIK3CA</i> mutations account for 93% of all variants detected and predict poor overall survival in MBC (hazard ratio = 3.461; 95% CI, 1.866 to 6.42; <i>P</i> = .001). Patients with MBC had higher plasma cell-free DNA levels, higher variant allele frequencies, and more polyclonal variants, notably in <i>ESR1</i> than in all other groups. Only 15 individuals had evidence of potential clonal hematopoiesis of indeterminate potential mutations.<h4>Conclusion</h4>We were able detect ctDNA across the breast cancer spectrum, notably in MBC where variants in <i>ESR1</i>, <i>TP53</i>, and <i>PIK3CA</i> predicted poor overall survival. The assay could be used to monitor emergence of resistance mutations such as in <i>ESR1</i> that herald resistance to aromatase inhibitors to tailor adjuvant therapies. However, we suggest caution is needed when interpreting results from a single plasma sample as variants were also detected in a small proportion of HCs.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Humans, Breast Neoplasms, Neoplasm Metastasis, Estrogen Receptor alpha, Aromatase Inhibitors, Survival Analysis, Case-Control Studies, Drug Resistance, Neoplasm, Mutation, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Tumor Suppressor Protein p53, Class I Phosphatidylinositol 3-Kinases, High-Throughput Nucleotide Sequencing, Biomarkers, Tumor, Circulating Tumor DNA |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 18 Oct 2022 13:34 |
| Last Modified: | 13 Apr 2023 19:09 |
| DOI: | 10.1200/PO.20.00522 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3165595 |
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