Johnston S, et al. - The effects of combination palbociclib plus letrozole as neoadjuvant therapy were evaluated in PALLET, a phase 2 randomized trial. Researchers randomly assigned postmenopausal women with estrogen receptor (ER)-positive primary breast cancer (BC) and tumors greater than or equal to 2.0 cm 3:2:2:2 to letrozole (2.5 mg/d) for 14 weeks (A); letrozole for 2 weeks, then palbociclib plus letrozole to 14 weeks (B); palbociclib for 2 weeks, then palbociclib plus letrozole to 14 weeks (C); or palbociclib plus letrozole for 14 weeks. Outcomes revealed significant improvement in suppression of malignant cell proliferation (Ki-67) in primary ER-positive BC with the addition of palbociclib to letrozole but with no increase in clinical response rate over 14 weeks. This may have been related to a concurrent reduction in apoptosis.