A digital RNA signature of Circulating Tumor Cells predicting early therapeutic response in localized and metastatic breast cancer. - PubMed - NCBI

A digital RNA signature of Circulating Tumor Cells predicting early therapeutic response in localized and metastatic breast cancer. - PubMed - NCBI

Cancer Discov. 2018 Aug 13. pii: CD-18-0432. doi: 10.1158/2159-8290.CD-18-0432. [Epub ahead of print]

A digital RNA signature of Circulating Tumor Cells predicting early therapeutic response in localized and metastatic breast cancer.

Kwan TT1, Bardia A2, Spring LM2, Giobbie-Hurder A3, Kalinich M4, Dubash T5, Sundaresan T6, Hong X4, LiCausi JA7, Ho U4, Silva EJ4, Wittner BS8, Sequist LV7, Kapur R4, Miyamoto DT4, Toner M9, Haber DA10, Maheswaran S7.

Author information

Abstract

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 four weeks of treatment (p=0.01). In the subset with estrogen receptor (ER)-positive disease, failure to suppress ER-signaling within CTCs after three 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.

PMID:

 

30104333

 

DOI:

 

10.1158/2159-8290.CD-18-0432