HER2-enriched subtype and ERBB2 mRNA as predictors of pathological complete response following trastuzumab and lapatinib without chemotherapy in early-stage HER2-positive breast cancer: A combined analysis of TBCRC006/023 and PAMELA trials.

509Background: HER2-Enriched (HER2-E) intrinsic subtype within HER2-positive breast cancer is characterized by high expression of ERBB2 and related genes. Here we retrospectively evaluated the value of the HER2-E subtype and ERBB2 mRNA expression alone to predict pathological complete response (pCR) in tumor samples from PAMELA and TBCRC 006/023 trials. Methods: All patients had HER2-positive early breast cancer and were treated with neoadjuvant lapatinib and trastuzumab. Patients with hormone receptor-positive tumors were also treated with letrozole or tamoxifen. In PAMELA (NCT01973660), 151 patients were treated for 18 weeks. TBCRC 006 (NCT00548184) treated 66 patients for 12 weeks and TBCRC 023 (NCT00999804) randomized 97 patients to 12 vs. 24 weeks of treatment. pCR was defined as no residual invasive carcinoma in the breast. Baseline intrinsic subtypes and ERBB2 mRNA expression were determined using the nCounter-based PAM50 predictor. ERBB2 expression was dichotomized as low (lowest 1/3) vs high (hig...