Evaluation of endocrine resistance using ESR1 genotyping of circulating tumor cells and plasma DNA.

Breast Neoplasms Circulating Tumor DNA Estrogen Receptor alpha / genetics Female Genotype Humans Mutation Neoplasm Recurrence, Local Neoplastic Cells, Circulating Prospective Studies
AI resistance ER + breast cancer Acquired ESR1 mutations Circulating tumor DNA (ctDNA) Circulating tumor cells (CTCs) High-sensitivity ESR1 sequencing

Journal

Breast cancer research and treatment
ISSN: 1573-7217
Titre abrégé: Breast Cancer Res Treat
Pays: Netherlands
ID NLM: 8111104

Informations de publication

Date de publication:
Jul 2021
Historique:
received: 17 12 2020
accepted: 24 05 2021
pubmed: 9 6 2021
medline: 30 6 2021
entrez: 8 6 2021
Statut: ppublish

Résumé

Therapeutic efficacy of hormonal therapies to target estrogen receptor (ER)-positive breast cancer is limited by the acquisition of ligand-independent ESR1 mutations, which confer treatment resistance to aromatase inhibitors (AIs). Monitoring for the emergence of such mutations may enable individualized therapy. We thus assessed CTC- and ctDNA-based detection of ESR1 mutations with the aim of evaluating non-invasive approaches for the determination of endocrine resistance. In a prospective cohort of 55 women with hormone receptor-positive metastatic breast cancer, we isolated circulating tumor cells (CTCs) and developed a high-sensitivity method for the detection of ESR1 mutations in these CTCs. In patients with sufficient plasma for the simultaneous extraction of circulating tumor DNA (ctDNA), we performed a parallel analysis of ESR1 mutations using multiplex droplet digital PCR (ddPCR) and examined the agreement between these two platforms. Finally, we isolated single CTCs from a subset of these patients and reviewed RNA expression to explore alternate methods of evaluating endocrine responsiveness. High-sensitivity ESR1 sequencing from CTCs revealed mono- and oligoclonal mutations in 22% of patients. These were concordant with plasma DNA sequencing in 95% of cases. Emergence of ESR1 mutations was correlated both with time to metastatic relapse and duration of AI therapy following such recurrence. The Presence of an ESR1 mutation, compared to ESR1 wild type, was associated with markedly shorter Progression-Free Survival on AI-based therapies (p = 0.0006), but unaltered to other non-AI-based therapies (p = 0.73). Compared with ESR1 mutant cases, AI-resistant CTCs with wild-type ESR1 showed an elevated ER-coactivator RNA signature, consistent with their predicted response to second-line hormonal therapies. Blood-based serial monitoring may guide the selection of precision therapeutics for women with AI-resistant ER-positive breast cancer.

Identifiants

DOI: 10.1007/s10549-021-06270-z PMID: 34101078 PMC: PMC8667563
pubmed: 34101078
doi: 10.1007/s10549-021-06270-z
pii: 10.1007/s10549-021-06270-z
pmc: PMC8667563
mid: NIHMS1756429
doi:

Substances chimiques

Circulating Tumor DNA 0
Estrogen Receptor alpha 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

43-52

Subventions

Organisme : NIA NIH HHS
ID : T35 AG049685
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA129933
Pays : United States
Organisme : National Institute of Health
ID : 2RO1CA129933
Organisme : NIBIB NIH HHS
ID : U01 EB012493
Pays : United States
Organisme : Susan G Komen Foundation
ID : CCR15224703
Organisme : National Institute of Health
ID : 5U01EB012493
Organisme : NCI NIH HHS
ID : K12 CA087723
Pays : United States
Organisme : Federal Share Research Career Development Award
ID : K12CA087723
Organisme : National Institute of Health
ID : 5P41EB002503
Organisme : NIBIB NIH HHS
ID : P41 EB002503
Pays : United States
Organisme : National Institute of Health
ID : 2U01EB012493

Références

Nat Rev Clin Oncol. 2015 Oct;12(10):573-83
pubmed: 26122181
Proc Natl Acad Sci U S A. 2016 May 3;113(18):4970-5
pubmed: 27084884
Nat Genet. 2017 Mar;49(3):444-450
pubmed: 28112739
Nat Genet. 2013 Dec;45(12):1446-51
pubmed: 24185510
Cell Rep. 2013 Sep 26;4(6):1116-30
pubmed: 24055055
J Natl Cancer Inst. 2003 Mar 5;95(5):353-61
pubmed: 12618500
JAMA Oncol. 2016 Oct 1;2(10):1310-1315
pubmed: 27532364
Cancer Res. 2013 Dec 1;73(23):6856-64
pubmed: 24217577
Clin Cancer Res. 2014 Apr 1;20(7):1757-1767
pubmed: 24398047
J Biol Chem. 2000 Dec 29;275(52):40810-6
pubmed: 11010967
J Clin Oncol. 2016 Sep 1;34(25):3069-103
pubmed: 27217461
Cell Rep. 2014 Sep 25;8(6):1905-1918
pubmed: 25242334
Clin Cancer Res. 2017 Oct 15;23(20):6086-6093
pubmed: 28679775
Cancer Res. 2008 Jan 1;68(1):301-6
pubmed: 18172323
Science. 1999 Jun 25;284(5423):2174-7
pubmed: 10381882
Clin Cancer Res. 2016 Feb 15;22(4):993-9
pubmed: 26261103
Oncotarget. 2016 May 31;7(22):32504-18
pubmed: 27102299
J Clin Oncol. 2016 Sep 1;34(25):2961-8
pubmed: 27269946
Oncotarget. 2016 Aug 19;8(40):66901-66911
pubmed: 28978004
Sci Transl Med. 2015 Nov 11;7(313):313ra182
pubmed: 26560360
Science. 2020 Mar 27;367(6485):1468-1473
pubmed: 32029688
Nat Genet. 2013 Dec;45(12):1439-45
pubmed: 24185512
Cancer Discov. 2018 Oct;8(10):1286-1299
pubmed: 30104333
Eur J Cancer. 2019 Jan;106:133-143
pubmed: 30528798
Clin Cancer Res. 2016 Mar 1;22(5):1103-10
pubmed: 26446944
Science. 2014 Jul 11;345(6193):216-20
pubmed: 25013076
Clin Chem. 2015 Jul;61(7):974-82
pubmed: 25979954
Int J Cancer. 2015 Nov 15;137(10):2513-9
pubmed: 25994408
Mol Oncol. 2018 Jan;12(1):48-57
pubmed: 29063679
Sci Transl Med. 2013 Apr 3;5(179):179ra47
pubmed: 23552373

Auteurs

Tilak K Sundaresan (TK)

Cancer Center, Massachusetts General Hospital, Bldg 149, 13th Street, Charlestown, MA, 02129, USA.
Division of Oncology, San Francisco Medical Center, San Francisco, CA, USA.
Harvard Medical School, Boston, MA, 02115, USA.

Taronish D Dubash (TD)

Cancer Center, Massachusetts General Hospital, Bldg 149, 13th Street, Charlestown, MA, 02129, USA.
Harvard Medical School, Boston, MA, 02115, USA.

Zongli Zheng (Z)

Cancer Center, Massachusetts General Hospital, Bldg 149, 13th Street, Charlestown, MA, 02129, USA.
Department of Pathology, Massachusetts General Hospital, Boston, MA, 02114, USA.
Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China.
Harvard Medical School, Boston, MA, 02115, USA.

Aditya Bardia (A)

Cancer Center, Massachusetts General Hospital, Bldg 149, 13th Street, Charlestown, MA, 02129, USA.
Department of Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA.
Harvard Medical School, Boston, MA, 02115, USA.

Ben S Wittner (BS)

Cancer Center, Massachusetts General Hospital, Bldg 149, 13th Street, Charlestown, MA, 02129, USA.
Harvard Medical School, Boston, MA, 02115, USA.

Nicola Aceto (N)

Cancer Center, Massachusetts General Hospital, Bldg 149, 13th Street, Charlestown, MA, 02129, USA.
Department of Biomedicine, University of Basel and University Hospital Basel, Basel, Switzerland.
Harvard Medical School, Boston, MA, 02115, USA.

Erin J Silva (EJ)

Cancer Center, Massachusetts General Hospital, Bldg 149, 13th Street, Charlestown, MA, 02129, USA.
Harvard Medical School, Boston, MA, 02115, USA.

Douglas B Fox (DB)

Cancer Center, Massachusetts General Hospital, Bldg 149, 13th Street, Charlestown, MA, 02129, USA.
Harvard Medical School, Boston, MA, 02115, USA.

Matthew Liebers (M)

Cancer Center, Massachusetts General Hospital, Bldg 149, 13th Street, Charlestown, MA, 02129, USA.
Harvard Medical School, Boston, MA, 02115, USA.

Ravi Kapur (R)

MicroMedicine, Inc., Waltham, MA, 02451, USA.

John Iafrate (J)

Cancer Center, Massachusetts General Hospital, Bldg 149, 13th Street, Charlestown, MA, 02129, USA.
Department of Pathology, Massachusetts General Hospital, Boston, MA, 02114, USA.
Harvard Medical School, Boston, MA, 02115, USA.

Mehmet Toner (M)

Cancer Center, Massachusetts General Hospital, Bldg 149, 13th Street, Charlestown, MA, 02129, USA.
Department of Surgery, Center for Engineering in Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA.
Shriners Hospitals for Children, Boston, MA, 02114, USA.
Department of Surgery, Massachusetts General Hospital, Boston, MA, 02114, USA.
Harvard Medical School, Boston, MA, 02115, USA.

Shyamala Maheswaran (S)

Cancer Center, Massachusetts General Hospital, Bldg 149, 13th Street, Charlestown, MA, 02129, USA. maheswaran@helix.mgh.harvard.edu.
Department of Surgery, Massachusetts General Hospital, Boston, MA, 02114, USA. maheswaran@helix.mgh.harvard.edu.
Harvard Medical School, Boston, MA, 02115, USA. maheswaran@helix.mgh.harvard.edu.
ORCID: 0000-0002-9356-1709

Daniel A Haber (DA)

Cancer Center, Massachusetts General Hospital, Bldg 149, 13th Street, Charlestown, MA, 02129, USA. dhaber@mgh.harvard.edu.
Department of Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA. dhaber@mgh.harvard.edu.
Howard Hughes Medical Institute, Bethesda, MD, 20851, USA. dhaber@mgh.harvard.edu.
Harvard Medical School, Boston, MA, 02115, USA. dhaber@mgh.harvard.edu.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Maladies du sein › Tumeurs du sein › Evaluation of endocrine resistance using ESR1...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ADN › ADN tumoral › ADN tumoral circulant › Evaluation of endocrine resistance using ESR1...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Récepteurs cytoplasmiques et nucléaires › Récepteur alpha des oestrogènes › Evaluation of endocrine resistance using ESR1...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Evaluation of endocrine resistance using ESR1...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Evaluation of endocrine resistance using ESR1...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Evaluation of endocrine resistance using ESR1...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Récidive tumorale locale › Evaluation of endocrine resistance using ESR1...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Métastase tumorale › Cellules tumorales circulantes › Evaluation of endocrine resistance using ESR1...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études prospectives › Evaluation of endocrine resistance using ESR1...