307 patients were randomized to LET (n=103) or LET+PALBO (n=204) for 14 wks...Lower levels of ER, higher levels of cyclin-E1, and amplification of cyclin-D1 were each significantly associated with a greater chance of non-CCCA with LET+PALBO….These results suggest that multiple identifiable mechanisms of de novo resistance to PALBO are likely to exist in primary ER+ BC.