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12.05.2017 | Clinical trial | Ausgabe 3/2017

Breast Cancer Research and Treatment 3/2017

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

Zeitschrift:
Breast Cancer Research and Treatment > Ausgabe 3/2017
Autoren:
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
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1007/​s10549-017-4257-x) contains supplementary material, which is available to authorized users.
An erratum to this article is available at http://​dx.​doi.​org/​10.​1007/​s10549-017-4339-9.

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.

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