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Hybrid capture-based genomic profiling of circulating tumor DNA from patients with estrogen receptor-positive metastatic breast cancer.
Ann Oncol 2017; 28(11):2866-2873AO

Abstract

Background

Genomic changes that occur in breast cancer during the course of disease have been informed by sequencing of primary and metastatic tumor tissue. For patients with relapsed and metastatic disease, evolution of the breast cancer genome highlights the importance of using a recent sample for genomic profiling to guide clinical decision-making. Obtaining a metastatic tissue biopsy can be challenging, and analysis of circulating tumor DNA (ctDNA) from blood may provide a minimally invasive alternative.

Patients and methods

Hybrid capture-based genomic profiling was carried out on ctDNA from 254 female patients with estrogen receptor-positive breast cancer. Peripheral blood samples were submitted by clinicians in the course of routine clinical care between May 2016 and March 2017. Sequencing of 62 genes was carried out to a median unique coverage depth of 7503×. Genomic alterations (GAs) in ctDNA were evaluated and compared with matched tissue samples and genomic datasets of tissue from breast cancer.

Results

At least 1 GA was reported in 78% of samples. Frequently altered genes were TP53 (38%), ESR1 (31%) and PIK3CA (31%). Temporally matched ctDNA and tissue samples were available for 14 patients; 89% of mutations detected in tissue were also detected in ctDNA. Diverse ESR1 GAs including mutation, rearrangement and amplification, were observed. Multiple concurrent ESR1 GAs were observed in 40% of ESR1-altered cases, suggesting polyclonal origin; ESR1 compound mutations were also observed in two cases. ESR1-altered cases harbored co-occurring GAs in PIK3CA (35%), FGFR1 (16%), ERBB2 (8%), BRCA1/2 (5%), and AKT1 (4%).

Conclusions

GAs relevant to relapsed/metastatic breast cancer management were identified, including diverse ESR1 GAs. Genomic profiling of ctDNA demonstrated sensitive detection of mutations found in tissue. Detection of amplifications was associated with ctDNA fraction. Genomic profiling of ctDNA may provide a complementary and possibly alternative approach to tissue-based genomic testing for patients with estrogen receptor-positive metastatic breast cancer.

Authors+Show Affiliations

Foundation Medicine, Inc., Cambridge.Foundation Medicine, Inc., Cambridge.Foundation Medicine, Inc., Cambridge.Foundation Medicine, Inc., Cambridge.Foundation Medicine, Inc., Cambridge.Foundation Medicine, Inc., Cambridge.Avera Cancer Institute, Sioux Falls.Baylor University Medical Center, Texas Oncology, US Oncology, Dallas.Foundation Medicine, Inc., Cambridge.Sarah Cannon Research Institute, Nashville.Foundation Medicine, Inc., Cambridge.Eastchester Center for Cancer Care, Bronx.Foundation Medicine, Inc., Cambridge.Foundation Medicine, Inc., Cambridge.Foundation Medicine, Inc., Cambridge.Sutter Medical Group of the Redwoods, Santa Rosa.Division of Medical Oncology, Department of Medicine, Rutgers Cancer Institute of New Jersey, New Brunswick.Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore.Weill Cornell Breast Center, Weill Cornell Medicine, New York.Avera Cancer Institute, Sioux Falls.Foundation Medicine, Inc., Cambridge. Tufts University Medical Center, Boston.Department of Breast Medical Oncology, Yale University, Yale Cancer Center, New Haven.Baylor University Medical Center, Texas Oncology, US Oncology, Dallas.Foundation Medicine, Inc., Cambridge.Foundation Medicine, Inc., Cambridge. Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, USA.Foundation Medicine, Inc., Cambridge.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28945887

Citation

Chung, J H., et al. "Hybrid Capture-based Genomic Profiling of Circulating Tumor DNA From Patients With Estrogen Receptor-positive Metastatic Breast Cancer." Annals of Oncology : Official Journal of the European Society for Medical Oncology, vol. 28, no. 11, 2017, pp. 2866-2873.
Chung JH, Pavlick D, Hartmaier R, et al. Hybrid capture-based genomic profiling of circulating tumor DNA from patients with estrogen receptor-positive metastatic breast cancer. Ann Oncol. 2017;28(11):2866-2873.
Chung, J. H., Pavlick, D., Hartmaier, R., Schrock, A. B., Young, L., Forcier, B., ... Ali, S. M. (2017). Hybrid capture-based genomic profiling of circulating tumor DNA from patients with estrogen receptor-positive metastatic breast cancer. Annals of Oncology : Official Journal of the European Society for Medical Oncology, 28(11), pp. 2866-2873. doi:10.1093/annonc/mdx490.
Chung JH, et al. Hybrid Capture-based Genomic Profiling of Circulating Tumor DNA From Patients With Estrogen Receptor-positive Metastatic Breast Cancer. Ann Oncol. 2017 Nov 1;28(11):2866-2873. PubMed PMID: 28945887.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hybrid capture-based genomic profiling of circulating tumor DNA from patients with estrogen receptor-positive metastatic breast cancer. AU - Chung,J H, AU - Pavlick,D, AU - Hartmaier,R, AU - Schrock,A B, AU - Young,L, AU - Forcier,B, AU - Ye,P, AU - Levin,M K, AU - Goldberg,M, AU - Burris,H, AU - Gay,L M, AU - Hoffman,A D, AU - Stephens,P J, AU - Frampton,G M, AU - Lipson,D M, AU - Nguyen,D M, AU - Ganesan,S, AU - Park,B H, AU - Vahdat,L T, AU - Leyland-Jones,B, AU - Mughal,T I, AU - Pusztai,L, AU - O'Shaughnessy,J, AU - Miller,V A, AU - Ross,J S, AU - Ali,S M, PY - 2017/9/26/pubmed PY - 2018/3/3/medline PY - 2017/9/26/entrez KW - ER KW - ESR1 KW - ctDNA KW - genomic profiling KW - liquid biopsy KW - metastatic breast cancer SP - 2866 EP - 2873 JF - Annals of oncology : official journal of the European Society for Medical Oncology JO - Ann. Oncol. VL - 28 IS - 11 N2 - Background: Genomic changes that occur in breast cancer during the course of disease have been informed by sequencing of primary and metastatic tumor tissue. For patients with relapsed and metastatic disease, evolution of the breast cancer genome highlights the importance of using a recent sample for genomic profiling to guide clinical decision-making. Obtaining a metastatic tissue biopsy can be challenging, and analysis of circulating tumor DNA (ctDNA) from blood may provide a minimally invasive alternative. Patients and methods: Hybrid capture-based genomic profiling was carried out on ctDNA from 254 female patients with estrogen receptor-positive breast cancer. Peripheral blood samples were submitted by clinicians in the course of routine clinical care between May 2016 and March 2017. Sequencing of 62 genes was carried out to a median unique coverage depth of 7503×. Genomic alterations (GAs) in ctDNA were evaluated and compared with matched tissue samples and genomic datasets of tissue from breast cancer. Results: At least 1 GA was reported in 78% of samples. Frequently altered genes were TP53 (38%), ESR1 (31%) and PIK3CA (31%). Temporally matched ctDNA and tissue samples were available for 14 patients; 89% of mutations detected in tissue were also detected in ctDNA. Diverse ESR1 GAs including mutation, rearrangement and amplification, were observed. Multiple concurrent ESR1 GAs were observed in 40% of ESR1-altered cases, suggesting polyclonal origin; ESR1 compound mutations were also observed in two cases. ESR1-altered cases harbored co-occurring GAs in PIK3CA (35%), FGFR1 (16%), ERBB2 (8%), BRCA1/2 (5%), and AKT1 (4%). Conclusions: GAs relevant to relapsed/metastatic breast cancer management were identified, including diverse ESR1 GAs. Genomic profiling of ctDNA demonstrated sensitive detection of mutations found in tissue. Detection of amplifications was associated with ctDNA fraction. Genomic profiling of ctDNA may provide a complementary and possibly alternative approach to tissue-based genomic testing for patients with estrogen receptor-positive metastatic breast cancer. SN - 1569-8041 UR - https://www.unboundmedicine.com/medline/citation/28945887/Hybrid_capture_based_genomic_profiling_of_circulating_tumor_DNA_from_patients_with_estrogen_receptor_positive_metastatic_breast_cancer_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0923-7534(19)34609-5 DB - PRIME DP - Unbound Medicine ER -