A Digital RNA Signature of Circulating Tumor Cells Predicting Early Therapeutic Response in Localized and Metastatic Breast Cancer.

Autor:	Kwan TT; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts., Bardia A; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts.; Division of Medical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Spring LM; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts.; Division of Medical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Giobbie-Hurder A; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts., Kalinich M; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts., Dubash T; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts., Sundaresan T; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts., Hong X; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts., LiCausi JA; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts., Ho U; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts., Silva EJ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts., Wittner BS; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts., Sequist LV; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts.; Division of Medical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Kapur R; Center for Bioengineering in Medicine, Massachusetts General Hospital and Harvard Medical School, and Shriners Hospital for Children, Boston, Massachusetts., Miyamoto DT; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts.; Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Toner M; Center for Bioengineering in Medicine, Massachusetts General Hospital and Harvard Medical School, and Shriners Hospital for Children, Boston, Massachusetts.; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Haber DA; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts. dhaber@mgh.harvard.edu maheswaran@helix.mgh.harvard.edu.; Division of Medical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.; Howard Hughes Medical Institute, Chevy Chase, Maryland., Maheswaran S; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts. dhaber@mgh.harvard.edu maheswaran@helix.mgh.harvard.edu.; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Jazyk:	angličtina
Zdroj:	Cancer discovery [Cancer Discov] 2018 Oct; Vol. 8 (10), pp. 1286-1299. Date of Electronic Publication: 2018 Aug 13.
DOI:	10.1158/2159-8290.CD-18-0432
Abstrakt:	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 . (©2018 American Association for Cancer Research.)
Databáze:	MEDLINE
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