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Breast Cancer Research and Treatment

, Volume 164, Issue 3, pp 627–638 | Cite as

Comparative clinical utility of tumor genomic testing and cell-free DNA in metastatic breast cancer

  • Kara N. Maxwell
  • Danielle Soucier-Ernst
  • Emin Tahirovic
  • Andrea B. Troxel
  • Candace Clark
  • Michael Feldman
  • Christopher Colameco
  • Bijal Kakrecha
  • Melissa Langer
  • David Lieberman
  • Jennifer J. D. Morrissette
  • Matt R. Paul
  • Tien-chi Pan
  • Stephanie Yee
  • Natalie Shih
  • Erica Carpenter
  • Lewis A. Chodosh
  • Angela DeMichele
Clinical trial

Abstract

Purpose

Breast cancer metastases differ biologically from primary disease; therefore, metastatic biopsies may assist in treatment decision making. Commercial genomic testing of both tumor and circulating tumor DNA have become available clinically, but utility of these tests in breast cancer management remains unclear.

Methods

Patients undergoing a clinically indicated metastatic tumor biopsy were consented to the ongoing METAMORPH registry. Tumor and blood were collected at the time of disease progression before subsequent therapy, and patients were followed for response on subsequent treatment. Tumor testing (n = 53) and concurrent cell-free DNA (n = 32) in a subset of patients was performed using CLIA-approved assays.

Results

The proportion of patients with a genomic alteration was lower in tumor than in blood (69 vs. 91%; p = 0.06). After restricting analysis to alterations covered on both platforms, 83% of tumor alterations were detected in blood, while 90% of blood alterations were detected in tumor. Mutational load specific for the panel genes was calculated for both tumor and blood. Time to progression on subsequent treatment was significantly shorter for patients whose tumors had high panel-specific mutational load (HR 0.31, 95% CI 0.12–0.78) or a TP53 mutation (HR 0.35, 95% CI 0.20–0.79), after adjusting for stage at presentation, hormone receptor status, prior treatment type, and number of lines of metastatic treatment.

Conclusions

Treating oncologists must distinguish platform differences from true biological heterogeneity when comparing tumor and cfDNA genomic testing results. Tumor and concurrent cfDNA contribute unique genomic information in metastatic breast cancer patients, providing potentially useful biomarkers for aggressive metastatic disease.

Keywords

Metastatic breast cancer Liquid biopsy Cell-free DNA Genomic testing Massively parallel sequencing 

Notes

Acknowledgements

We would like to acknowledge the research cases as well as the funding agencies that made this research possible and the assistance of Guardant Health in performing the cfDNA assays. This work was supported by the Translational Center of Excellence in Breast Cancer of the Abramson Cancer Center, University of Pennsylvania. K.N.M. and A.D.M had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. The authors declare that they have no conflict of interest. The experiments performed within comply with the current ethical standards and laws of the United States of America.

Supplementary material

10549_2017_4257_MOESM1_ESM.pdf (1.3 mb)
Supplementary material 1 (PDF 1372 kb)
10549_2017_4257_MOESM2_ESM.xlsx (220 kb)
Supplementary material 2 (XLSX 220 kb)

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Kara N. Maxwell
    • 1
  • Danielle Soucier-Ernst
    • 2
  • Emin Tahirovic
    • 3
  • Andrea B. Troxel
    • 7
  • Candace Clark
    • 2
  • Michael Feldman
    • 4
  • Christopher Colameco
    • 2
  • Bijal Kakrecha
    • 1
  • Melissa Langer
    • 8
  • David Lieberman
    • 4
  • Jennifer J. D. Morrissette
    • 4
  • Matt R. Paul
    • 5
  • Tien-chi Pan
    • 5
  • Stephanie Yee
    • 1
  • Natalie Shih
    • 4
  • Erica Carpenter
    • 1
    • 2
  • Lewis A. Chodosh
    • 2
    • 5
    • 6
  • Angela DeMichele
    • 1
    • 2
    • 3
  1. 1.Department of Medicine, Division of Hematology-OncologyPerelman School of Medicine at the University of PennsylvaniaPhiladelphiaUSA
  2. 2.Abramson Cancer CenterPerelman School of Medicine at the University of PennsylvaniaPhiladelphiaUSA
  3. 3.Department of Biostatistics and EpidemiologyPerelman School of Medicine at the University of PennsylvaniaPhiladelphiaUSA
  4. 4.Department of Pathology and Laboratory MedicinePerelman School of Medicine at the University of PennsylvaniaPhiladelphiaUSA
  5. 5.Department of Cancer BiologyPerelman School of Medicine at the University of PennsylvaniaPhiladelphiaUSA
  6. 6.Department of Medicine, Division of EndocrinologyDiabetes and Metabolism at the Perelman School of Medicine at the University of PennsylvaniaPhiladelphiaUSA
  7. 7.Department of Population HealthNYU School of MedicineNew YorkUSA
  8. 8.University of Maryland School of MedicineBaltimoreUSA

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