Many hormone receptor-positive tumors show primary or acquired resistance, possibly because of a crosstalk with other growth factor-related transduction pathways (mainly epidermal growth factor receptor family related). The LETLOB study is a European multicenter, placebo-controlled, randomized phase II trial in postmenopausal patients with hormone-sensitive, HER2-negative, stage II-IIIA (T > 2 cm, N0-1, M0) breast cancer, in which letrozole or the combination of letrozole plus lapatinib will be administered for 6 months before surgery. Clinical endpoints (primary [ultrasonographic objective response], secondary [rate of pathologic complete response and of conservative surgery, safety, and time to treatment failure], and biologic [inhibition of intermediate and final biomarkers of the proliferative and apoptosis pathways and gene profile correlation with response]) will be evaluated.