High ctDNA molecule numbers relate with poor outcome in advanced ER+, HER2- postmenopausal breast cancer patients treated with everolimus and exemestane

Dinja T Kruger, Maurice P H M Jansen, Inge R H M Konings, Wouter M Dercksen, Agnes Jager, Jamal Oulad Hadj, Stefan Sleijfer, John W M Martens, Epie Boven

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

We determined whether progression-free survival (PFS) in metastatic breast cancer (MBC) patients receiving everolimus plus exemestane (EVE/EXE) varies depending on circulating tumour DNA (ctDNA) characteristics. Baseline plasma cell-free DNA (cfDNA) from 164 postmenopausal women with ER-positive, HER2-negative MBC refractory to a non-steroidal aromatase inhibitor and treated with standard EVE/EXE (Everolimus Biomarker Study, Eudract 2013-004120-11) was characterised for 10 relevant breast cancer genes by next generation sequencing with molecular barcoding. ctDNA molecule numbers, number of mutations and specific variants were related with PFS and overall survival (OS). Missense hotspot mutations in cfDNA were detected in 125 patients. The median of 54 ctDNA molecules per mL plasma distinguished patients with high and low/no ctDNA load. Patients with low/no ctDNA load (N=102) showed longer median PFS of 5.7 months (P=0.006) and OS of 124.8 months (P=0.008) than patients with high ctDNA load (N=62) (4.4 months and 107.7 months, respectively) in multivariate analyses. Patients with <3 specific mutations (N=135) had longer median PFS of 5.4 months compared to those with ≥3 mutations (3.4 months) (p<0.001). In conclusion, MBC patients with low/no ctDNA load or <3 hotspot mutations experience longer PFS while treated with EVE/EXE.

Original languageEnglish
JournalMolecular oncology
DOIs
Publication statusE-pub ahead of print - 16 Dec 2019

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