ESR1 mutations in circulating plasma tumor DNA from metastatic breast cancer patients

David Chu, Costanza Paoletti, Christina Gersch, Dustin A. VanDenBerg, Daniel J. Zabransky, Rory L. Cochran, Hong Yuen Wong, Patricia Valda Toro, Justin Cidado, Sarah Croessmann, Bracha Erlanger, Karen Cravero, Kelly Kyker-Snowman, Berry Button, Heather A. Parsons, W. Brian Dalton, Riaz Gillani, Arielle Medford, Kimberly Aung, Nahomi TokudomeArul M. Chinnaiyan, Anne Schott, Dan Robinson, Karen S. Jacks, Josh Lauring, Paula J. Hurley, Daniel F. Hayes, James M. Rae, Ben Ho Park

Research output: Contribution to journalArticlepeer-review

114 Scopus citations


Purpose: Mutations in the estrogen receptor (ER)a gene, ESR1, have been identified in breast cancer metastases after progression on endocrine therapies. Because of limitations of metastatic biopsies, the reported frequency of ESR1 mutations may be underestimated. Here, we show a high frequency of ESR1 mutations using circulating plasma tumorDNA(ptDNA) from patients with metastatic breast cancer. Experimental Design: We retrospectively obtained plasma samples from eight patients with known ESR1 mutations and three patients with wild-type ESR1 identified by next-generation sequencing (NGS) of biopsied metastatic tissues. Three common ESR1 mutations were queried for using droplet digital PCR (ddPCR). In a prospective cohort, metastatic tissue and plasma were collected contemporaneously from eight ER-positive and four ER-negative patients. Tissue biopsies were sequenced by NGS, and ptDNA ESR1 mutations were analyzed by ddPCR. Results: In the retrospective cohort, all corresponding mutations were detected in ptDNA, with two patients harboring additional ESR1 mutations not present in their metastatic tissues. In the prospective cohort, three ER-positive patients did not have adequate tissue for NGS, and no ESR1 mutations were identified in tissue biopsies from the other nine patients. In contrast, ddPCR detected seven ptDNA ESR1 mutations in 6 of 12 patients (50%). Conclusions: We show that ESR1 mutations can occur at a high frequency and suggest that blood can be used to identify additional mutations not found by sequencing of a single metastatic lesion.

Original languageEnglish (US)
Pages (from-to)993-999
Number of pages7
JournalClinical Cancer Research
Issue number4
StatePublished - Feb 15 2016

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Dive into the research topics of 'ESR1 mutations in circulating plasma tumor DNA from metastatic breast cancer patients'. Together they form a unique fingerprint.

Cite this