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Serial monitoring of genomic alterations in circulating tumor cells of ER‐positive/HER2‐negative advanced breast cancer: feasibility of precision oncology biomarker detection

التفاصيل البيبلوغرافية
العنوان: Serial monitoring of genomic alterations in circulating tumor cells of ER‐positive/HER2‐negative advanced breast cancer: feasibility of precision oncology biomarker detection
المؤلفون: Andi K. Cani, Emily M. Dolce, Elizabeth P. Darga, Kevin Hu, Chia‐Jen Liu, Jackie Pierce, Kieran Bradbury, Elaine Kilgour, Kimberly Aung, Gaia Schiavon, Danielle Carroll, T. Hedley Carr, Teresa Klinowska, Justin Lindemann, Gayle Marshall, Vicky Rowlands, Elizabeth A. Harrington, J. Carl Barrett, Nitharsan Sathiyayogan, Christopher Morrow, Valeria Sero, Anne C. Armstrong, Richard Baird, Erika Hamilton, Seock‐Ah Im, Komal Jhaveri, Manish R. Patel, Caroline Dive, Scott A. Tomlins, Aaron M. Udager, Daniel F. Hayes, Costanza Paoletti
المصدر: Molecular Oncology, Vol 16, Iss 10, Pp 1969-1985 (2022)
بيانات النشر: Wiley, 2022.
سنة النشر: 2022
المجموعة: LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
مصطلحات موضوعية: circulating tumor cells, circulating tumor DNA, liquid biopsy, precision medicine, tumor evolution, tumor heterogeneity, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
الوصف: Nearly all estrogen receptor (ER)‐positive (POS) metastatic breast cancers become refractory to endocrine (ET) and other therapies, leading to lethal disease presumably due to evolving genomic alterations. Timely monitoring of the molecular events associated with response/progression by serial tissue biopsies is logistically difficult. Use of liquid biopsies, including circulating tumor cells (CTC) and circulating tumor DNA (ctDNA), might provide highly informative, yet easily obtainable, evidence for better precision oncology care. Although ctDNA profiling has been well investigated, the CTC precision oncology genomic landscape and the advantages it may offer over ctDNA in ER‐POS breast cancer remain largely unexplored. Whole‐blood (WB) specimens were collected at serial time points from patients with advanced ER‐POS/HER2‐negative (NEG) advanced breast cancer in a phase I trial of AZD9496, an oral selective ER degrader (SERD) ET. Individual CTC were isolated from WB using tandem CellSearch®/DEPArray™ technologies and genomically profiled by targeted single‐cell DNA next‐generation sequencing (scNGS). High‐quality CTC (n = 123) from 12 patients profiled by scNGS showed 100% concordance with ctDNA detection of driver estrogen receptor α (ESR1) mutations. We developed a novel CTC‐based framework for precision medicine actionability reporting (MI‐CTCseq) that incorporates novel features, such as clonal predominance and zygosity of targetable alterations, both unambiguously identifiable in CTC compared to ctDNA. Thus, we nominated opportunities for targeted therapies in 73% of patients, directed at alterations in phosphatidylinositol‐4,5‐bisphosphate 3‐kinase catalytic subunit alpha (PIK3CA), fibroblast growth factor receptor 2 (FGFR2), and KIT proto‐oncogene, receptor tyrosine kinase (KIT). Intrapatient, inter‐CTC genomic heterogeneity was observed, at times between time points, in subclonal alterations. Our analysis suggests that serial monitoring of the CTC genome is feasible and should enable real‐time tracking of tumor evolution during progression, permitting more combination precision medicine interventions.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1878-0261
1574-7891
Relation: https://doaj.org/toc/1574-7891; https://doaj.org/toc/1878-0261
DOI: 10.1002/1878-0261.13150
URL الوصول: https://doaj.org/article/3982ed92674c47fd83894acff6f5a9d3
رقم الأكسشن: edsdoj.3982ed92674c47fd83894acff6f5a9d3
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:18780261
15747891
DOI:10.1002/1878-0261.13150