ER⁺ Breast Cancers Resistant to Prolonged Neoadjuvant Letrozole Exhibit an E2F4 Transcriptional Program Sensitive to CDK4/6 Inhibitors.

ABSTRACT: Purpose: This study aimed to identify biomarkers of resistance to endocrine therapy in estrogen receptor-positive (ER⁺) breast cancers treated with prolonged neoadjuvant letrozole.Experimental Design: We performed targeted DNA and RNA sequencing in 68 ER⁺ breast cancers from patients treated with preoperative letrozole (median, 7 months).Results: Twenty-four tumors (35%) exhibited a PEPI score ≥4 and/or recurred after a median of 58 months and were considered endocrine resistant. Integration of the 47 most upregulated genes (log FC > 1, FDR < 0.03) in letrozole-resistant tumors with transcription-binding data showed significant overlap with 20 E2F4-regulated genes (P = 2.56E-15). In patients treated with the CDK4/6 inhibitor palbociclib bef

SUBMITTER: Guerrero-Zotano AL 

PROVIDER: S-EPMC6690756 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature