PMID- 28679775
OWN - NLM
STAT- MEDLINE
DCOM- 20180523
LR  - 20210816
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 23
IP  - 20
DP  - 2017 Oct 15
TI  - Detection of Activating Estrogen Receptor Gene (ESR1) Mutations in Single 
      Circulating Tumor Cells.
PG  - 6086-6093
LID - 10.1158/1078-0432.CCR-17-1173 [doi]
AB  - Purpose: Early detection is essential for treatment plans before onset of 
      metastatic disease. Our purpose was to demonstrate feasibility to detect and 
      monitor estrogen receptor 1 (ESR1) gene mutations at the single circulating tumor 
      cell (CTC) level in metastatic breast cancer (MBC).Experimental Design: We used a 
      CTC molecular characterization approach to investigate heterogeneity of 14 
      hotspot mutations in ESR1 and their correlation with endocrine resistance. 
      Combining the CellSearch and DEPArray technologies allowed recovery of 71 single 
      CTCs and 12 WBC from 3 ER-positive MBC patients. Forty CTCs and 12 WBC were 
      subjected to whole genome amplification by MALBAC and Sanger sequencing.Results: 
      Among 3 selected patients, 2 had an ESR1 mutation (Y537). One showed two 
      different ESR1 variants in a single CTC and another showed loss of 
      heterozygosity. All mutations were detected in matched cell-free DNA (cfDNA). 
      Furthermore, one had 2 serial blood samples analyzed and showed changes in both 
      cfDNA and CTCs with emergence of mutations in ESR1 (Y537S and T570I), which has 
      not been reported previously.Conclusions: CTCs are easily accessible biomarkers 
      to monitor and better personalize management of patients with previously 
      demonstrated ER-MBC who are progressing on endocrine therapy. We showed that 
      single CTC analysis can yield important information on clonal heterogeneity and 
      can be a source of discovery of novel and potential driver mutations. Finally, we 
      also validate a workflow for liquid biopsy that will facilitate early detection 
      of ESR1 mutations, the emergence of endocrine resistance and the choice of 
      further target therapy. Clin Cancer Res; 23(20); 6086-93. (c)2017 AACR.
CI  - (c)2017 American Association for Cancer Research.
FAU - Paolillo, Carmela
AU  - Paolillo C
AD  - Department of Cancer Biology, Sidney Kimmel Medical College, Thomas Jefferson 
      University, Philadelphia Pennsylvania.
AD  - Institute of Biochemistry and Clinical Biochemistry, Laboratory of Clinical 
      Molecular and Personalized Diagnostics, Catholic University of the Sacred Heart, 
      Rome, Italy.
FAU - Mu, Zhaomei
AU  - Mu Z
AD  - Department of Medicine-Hematology and Oncology, Robert H. Lurie Comprehensive 
      Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, 
      Illinois.
FAU - Rossi, Giovanna
AU  - Rossi G
AD  - Department of Medicine-Hematology and Oncology, Robert H. Lurie Comprehensive 
      Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, 
      Illinois.
FAU - Schiewer, Matthew J
AU  - Schiewer MJ
AD  - Department of Cancer Biology, Sidney Kimmel Medical College, Thomas Jefferson 
      University, Philadelphia Pennsylvania.
FAU - Nguyen, Thomas
AU  - Nguyen T
AD  - Department of Cancer Biology, Sidney Kimmel Medical College, Thomas Jefferson 
      University, Philadelphia Pennsylvania.
FAU - Austin, Laura
AU  - Austin L
AD  - Department of Cancer Biology, Sidney Kimmel Medical College, Thomas Jefferson 
      University, Philadelphia Pennsylvania.
FAU - Capoluongo, Ettore
AU  - Capoluongo E
AD  - Institute of Biochemistry and Clinical Biochemistry, Laboratory of Clinical 
      Molecular and Personalized Diagnostics, Catholic University of the Sacred Heart, 
      Rome, Italy.
FAU - Knudsen, Karen
AU  - Knudsen K
AD  - Department of Cancer Biology, Sidney Kimmel Medical College, Thomas Jefferson 
      University, Philadelphia Pennsylvania.
FAU - Cristofanilli, Massimo
AU  - Cristofanilli M
AD  - Department of Medicine-Hematology and Oncology, Robert H. Lurie Comprehensive 
      Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, 
      Illinois. paolo.fortina@jefferson.edu massimo.cristofanilli@nm.org.
FAU - Fortina, Paolo
AU  - Fortina P
AD  - Department of Cancer Biology, Sidney Kimmel Medical College, Thomas Jefferson 
      University, Philadelphia Pennsylvania. paolo.fortina@jefferson.edu 
      massimo.cristofanilli@nm.org.
AD  - Department of Molecular Medicine, Sapienza University, Rome, Italy.
LA  - eng
GR  - P30 CA056036/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20170705
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Circulating Tumor DNA)
RN  - 0 (ESR1 protein, human)
RN  - 0 (Estrogen Receptor alpha)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Biomarkers, Tumor
MH  - Cell Line, Tumor
MH  - Circulating Tumor DNA
MH  - DNA Mutational Analysis
MH  - Estrogen Receptor alpha/*genetics
MH  - Female
MH  - Humans
MH  - Liquid Biopsy
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - Neoplasm Metastasis
MH  - Neoplasm Staging
MH  - Neoplasms/*diagnosis/*genetics
MH  - Neoplastic Cells, Circulating/*metabolism/pathology
MH  - Proto-Oncogene Proteins B-raf/genetics
MH  - Reproducibility of Results
MH  - Workflow
PMC - PMC5641250
MID - NIHMS891111
COIS- The authors declare no conflict of interest.
EDAT- 2017/07/07 06:00
MHDA- 2018/05/24 06:00
PMCR- 2018/10/15
CRDT- 2017/07/07 06:00
PHST- 2017/04/26 00:00 [received]
PHST- 2017/06/20 00:00 [revised]
PHST- 2017/06/30 00:00 [accepted]
PHST- 2017/07/07 06:00 [pubmed]
PHST- 2018/05/24 06:00 [medline]
PHST- 2017/07/07 06:00 [entrez]
PHST- 2018/10/15 00:00 [pmc-release]
AID - 1078-0432.CCR-17-1173 [pii]
AID - 10.1158/1078-0432.CCR-17-1173 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2017 Oct 15;23(20):6086-6093. doi: 
      10.1158/1078-0432.CCR-17-1173. Epub 2017 Jul 5.