Evolution of Resistance in ER+ Breast Cancer

While the combination of endocrine therapy and CDK4/CDK6 inhibitors has been shown to be effective in the metastatic ER+ breast cancer setting, to test whether it is effective in an earlier stage neoadjuvant setting, the FELINE trial (NCT02712723) was established to test the efficacy of letrozole and ribociclib in a ER-positive, HER2-negative patients in a randomized, placebo-controlled, multicenter trial. Patients were randomized to one of three arms: those in Arm A received letrozole and placebo, Arm B letrozole and intermittent ribociclib, and Arm C letrozole and continuous ribociclib. Samples were collected at screening (Day 0), Cycle 1 (Day 14), and end of trial (Day 180). Samples from 24 patients, where cancer cells were present at Day 0 and one additional time point, were subjected to whole-exome sequencing profiling.]]>
The FELINE study included ER-positive and HER-negative early invasive breast cancer confirmed by core needle biopsy. Women had to be >= 18 years old, postmenopausal, have ECOG score 0-2, be ER+ in >= 66% of cells or ER Allred score 6-8, be HER2 negative, and clinical stage II or III.Patients were excluded if they were currently using other investigational agents, had inflammatory breast cancer, an excisional biopsy of this breast cancer, surgical axillary staging procedure, hormone replacement therapy, evidence of metastatic disease, clinically significant heart disease, or used certain herbal preparations or medications.]]>