Open AccessHigh ctDNA molecule numbers relate with poor outcome in advanced ER+, HER2− postmenopausal breast cancer patients treated with everolimus and exemestane
Author(s) -
Kruger Dinja T.,
Jansen Maurice P.H.M.,
Konings Inge R.H.M.,
Dercksen Wouter M.,
Jager Agnes,
Oulad Hadj Jamal,
Sleijfer Stefan,
Martens John W.M.,
Boven Epie
Publication year - 2020
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12617
Subject(s) - exemestane , medicine , everolimus , oncology , breast cancer , metastatic breast cancer , progression free survival , cancer , aromatase , chemotherapy
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 nonsteroidal 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.