Pathologic complete response (pCR) to dual human epidermal growth factor 2 (HER2)-targeted therapy was not significantly higher than single HER2 targeting, according to a study of 305 women with stage II to III HER2-positive breast cancer. Patients were randomly assigned to receive either paclitaxel plus trastuzumab alone (TH) or with lapatinib added (THL). Researchers found:

• pCR rate was 56% with THL and 46% with TH.

• Dual therapy showed no effect in the hormone receptor-positive subset, but a significant increase in pCR among the hormone receptor-negative subset.

• Tumors were molecularly heterogeneous by gene expression analysis using mRNA sequencing.

• pCR rates differed significantly by intrinsic subtype (HER2 enriched, 70%; luminal A, 34%; luminal B, 36%).

• In multivariable analysis, treatment arm, intrinsic subtype, HER2 amplicon gene expression, p53 mutation signature, and immune cell signature were all independently associated with pCR.

Citation: Carey LA, Berry DA, Cirrincione CT, et al. Molecular heterogeneity and response to neoadjuvant human epidermal growth factor receptor 2 targeting in CALGB 40601, a randomized phase III trial of paclitaxel plus trastuzumab with or without lapatinib. [Published online ahead of print November 2, 2015]. J Clin Oncol. doi: 10.1200/JCO.2015.62.1268.