title: Short report: Monitoring ESR1 mutations by circulating tumor DNA in aromatase inhibitor resistant metastatic breast cancer.
abstract: Acquired estrogen receptor gene (ESR1) mutations have been recently reported as a marker of resistance to aromatase inhibitors in hormone receptor positive metastatic breast cancer. We retrospectively considered seven patients treated for metastatic breast cancer with available samples from the primary tumor before any treatment, cryopreserved metastasis removed during progression and concomitant plasmas. All these seven patients were in disease progression after previous exposure to aromatase inhibitors for at least 6 months, and were assessed for ESR1 mutations detection in tumor and circulating DNA. For these patients, Sanger sequencing identified four metastases with clear ESR1 mutation and one possible, whereas digital PCR identified six mutated metastases. Then, under blind conditions and using digital PCR, corresponding circulating ESR1 mutations were successfully detected in four of these six metastatic breast cancer patients. Moreover, in two patients with serial blood samples following treatments exposure, the monitoring of circulating ESR1 mutations clearly predicted disease evolution. In the context of high interest for ESR1 mutations, our results highlight that these acquired recurrent mutations may be tracked in circulating tumor DNA and may be of clinical relevance for metastatic breast cancer patient monitoring.
authors.affiliation: INSERM U1079, Rouen, France.|Department of Gastroenterology, Rouen University Hospital, Rouen, France.|Equipe De Recherche En Oncologie (IRON), Rouen University Hospital and Centre Henri Becquerel, Rouen, France.
authors.forename: David
authors.initials: D
authors.lastname: Sefrioui
authors.affiliation: Equipe De Recherche En Oncologie (IRON), Rouen University Hospital and Centre Henri Becquerel, Rouen, France.|Department of Bio-Pathology, Centre Henri Becquerel, Rouen, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Perdrix
authors.affiliation: INSERM U1079, Rouen, France.|Equipe De Recherche En Oncologie (IRON), Rouen University Hospital and Centre Henri Becquerel, Rouen, France.
authors.forename: Nasrin
authors.initials: N
authors.lastname: Sarafan-Vasseur
authors.affiliation: Equipe De Recherche En Oncologie (IRON), Rouen University Hospital and Centre Henri Becquerel, Rouen, France.|Department of Pathology, Rouen University Hospital, Rouen, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Dolfus
authors.affiliation: Department of Surgery, Clinique Du Cèdre, Bois-Guillaume, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Dujon
authors.affiliation: Department of Bio-Pathology, Centre Henri Becquerel, Rouen, France.|INSERM U918, Centre Henri Becquerel, Rouen, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Picquenot
authors.affiliation: INSERM U1079, Rouen, France.|Equipe De Recherche En Oncologie (IRON), Rouen University Hospital and Centre Henri Becquerel, Rouen, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Delacour
authors.affiliation: Department of Bio-Pathology, Centre Henri Becquerel, Rouen, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Cornic
authors.affiliation: INSERM U918, Centre Henri Becquerel, Rouen, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Bohers
authors.affiliation: Department of Medical Oncology, Centre Henri Becquerel, Rouen, France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Leheurteur
authors.affiliation: Department of Medical Oncology, Centre Henri Becquerel, Rouen, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Rigal
authors.affiliation: Department of Medical Oncology, Centre Henri Becquerel, Rouen, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Tennevet
authors.affiliation: Equipe De Recherche En Oncologie (IRON), Rouen University Hospital and Centre Henri Becquerel, Rouen, France.|Department of Medical Oncology, Centre Henri Becquerel, Rouen, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Thery
authors.affiliation: Department of Medical Oncology, Centre Henri Becquerel, Rouen, France.
authors.forename: Cristina
authors.initials: C
authors.lastname: Alexandru
authors.affiliation: Department of Medical Oncology, Centre Henri Becquerel, Rouen, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Guillemet
authors.affiliation: Department of Medical Oncology, Centre Henri Becquerel, Rouen, France.
authors.forename: Cristian
authors.initials: C
authors.lastname: Moldovan
authors.affiliation: Department of Medical Oncology, Centre Henri Becquerel, Rouen, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Veyret
authors.affiliation: INSERM U1079, Rouen, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Frebourg
authors.affiliation: INSERM U1079, Rouen, France.|Department of Gastroenterology, Rouen University Hospital, Rouen, France.|Equipe De Recherche En Oncologie (IRON), Rouen University Hospital and Centre Henri Becquerel, Rouen, France.|Department of Medical Oncology, Centre Henri Becquerel, Rouen, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Di Fiore
authors.affiliation: Equipe De Recherche En Oncologie (IRON), Rouen University Hospital and Centre Henri Becquerel, Rouen, France.|INSERM U918, Centre Henri Becquerel, Rouen, France.|Department of Medical Oncology, Centre Henri Becquerel, Rouen, France.
authors.forename: Florian
authors.initials: F
authors.lastname: Clatot
mesh_terms: D047072:Aromatase Inhibitors / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000097:blood*; D019008:Drug Resistance, Neoplasm; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D006801:Humans; D009154:Mutation; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods*; D012189:Retrospective Studies
chemical_list: D047072:Aromatase Inhibitors; D004273:DNA, Neoplasm; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha
keywords: ESR1 mutations; aromatase inhibitor resistance; circulating tumor DNA; digital PCR; metastatic breast cancer