Early circulating tumor DNA dynamics and clonal selection with palbociclib and fulvestrant for breast cancer
Top Cited Papers
Open Access
- 1 March 2018
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 9 (1), 1-10
- https://doi.org/10.1038/s41467-018-03215-x
Abstract
CDK4/6 inhibition substantially improves progression-free survival (PFS) for women with advanced estrogen receptor-positive breast cancer, although there are no predictive biomarkers. Early changes in circulating tumor DNA (ctDNA) level may provide early response prediction, but the impact of tumor heterogeneity is unknown. Here we use plasma samples from patients in the randomized phase III PALOMA-3 study of CDK4/6 inhibitor palbociclib and fulvestrant for women with advanced breast cancer and show that relative change in PIK3CA ctDNA level after 15 days treatment strongly predicts PFS on palbociclib and fulvestrant (hazard ratio 3.94, log-rank p = 0.0013). ESR1 mutations selected by prior hormone therapy are shown to be frequently sub clonal, with ESR1 ctDNA dynamics offering limited prediction of clinical outcome. These results suggest that early ctDNA dynamics may provide a robust biomarker for CDK4/6 inhibitors, with early ctDNA dynamics demonstrating divergent response of tumor sub clones to treatment.This publication has 40 references indexed in Scilit:
- Early Evaluation of Circulating Tumor DNA as Marker of Therapeutic Efficacy in Metastatic Colorectal Cancer Patients (PLACOL Study)Clinical Cancer Research, 2017
- Phylogenetic ctDNA analysis depicts early-stage lung cancer evolutionNature, 2017
- Heterogeneity and clinical significance of ESR1 mutations in ER-positive metastatic breast cancer patients receiving fulvestrantNature Communications, 2016
- Quantitative assessment of BRAF V600 mutant circulating cell-free tumor DNA as a tool for therapeutic monitoring in metastatic melanoma patients treated with BRAF/MEK inhibitorsJournal of Translational Medicine, 2016
- Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancerScience Translational Medicine, 2015
- Multifocal clonal evolution characterized using circulating tumour DNA in a case of metastatic breast cancerNature Communications, 2015
- Mutation tracking in circulating tumor DNA predicts relapse in early breast cancerScience Translational Medicine, 2015
- Subclonal diversification of primary breast cancer revealed by multiregion sequencingNature Medicine, 2015
- First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm studyBritish Journal of Cancer, 2013
- ESR1 ligand-binding domain mutations in hormone-resistant breast cancerNature Genetics, 2013