American Association for Cancer Research
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Supplementary Tables from A Digital RNA Signature of Circulating Tumor Cells Predicting Early Therapeutic Response in Localized and Metastatic Breast Cancer

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posted on 2023-04-03, 21:22 authored by Tanya T. Kwan, Aditya Bardia, Laura M. Spring, Anita Giobbie-Hurder, Mark Kalinich, Taronish Dubash, Tilak Sundaresan, Xin Hong, Joseph A. LiCausi, Uyen Ho, Erin J. Silva, Ben S. Wittner, Lecia V. Sequist, Ravi Kapur, David T. Miyamoto, Mehmet Toner, Daniel A. Haber, Shyamala Maheswaran

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Breast Cancer Research Foundation

Howard Hughes Medical Institute

National Foundation for Cancer Research

MD/PhD Training

ESSCO Breast Cancer Research


Prostate Cancer Foundation



The multiplicity of new therapies for breast cancer presents a challenge for treatment selection. We describe a 17-gene digital signature of breast circulating tumor cell (CTC)–derived transcripts enriched from blood, enabling high-sensitivity early monitoring of response. In a prospective cohort of localized breast cancer, an elevated CTC score after three cycles of neoadjuvant therapy is associated with residual disease at surgery (P = 0.047). In a second prospective cohort with metastatic breast cancer, baseline CTC score correlates with overall survival (P = 0.02), as does persistent CTC signal after 4 weeks of treatment (P = 0.01). In the subset with estrogen receptor (ER)–positive disease, failure to suppress ER signaling within CTCs after 3 weeks of endocrine therapy predicts early progression (P = 0.008). Drug-refractory ER signaling within CTCs overlaps partially with presence of ESR1 mutations, pointing to diverse mechanisms of acquired endocrine drug resistance. Thus, CTC-derived digital RNA signatures enable noninvasive pharmacodynamic measurements to inform therapy in breast cancer.Significance: Digital analysis of RNA from CTCs interrogates treatment responses of both localized and metastatic breast cancer. Quantifying CTC-derived ER signaling during treatment identifies patients failing to respond to ER suppression despite having functional ESR1. Thus, noninvasive scoring of CTC-RNA signatures may help guide therapeutic choices in localized and advanced breast cancer. Cancer Discov; 8(10); 1286–99. ©2018 AACR.This article is highlighted in the In This Issue feature, p. 1195

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