Neoadjuvant Trastuzumab Response in Breast Cancer

HER2 (ERBB2) gene amplification and overexpression are present in 15-30% of invasive breast cancers. While HER2-targeted agents such as trastuzumab are effective treatments, therapeutic resistance remains a concern in HER2-positive breast cancer with 40-50% of patients having residual disease after neoadjuvant treatment with chemotherapy and trastuzumab. To investigate features that may make it possible to predict at diagnosis which cancers will be responsive to trastuzumab and chemotherapy, 48 tumor/normal DNA pairs extracted from pretreatment tumor biopsies and blood of HER2-positive breast cancer cases treated with neoadjuvant chemotherapy and trastuzumab were sequenced. Whole genome and exome sequence from tumor (average depth 49x and 71x) and normal (average depth 33x and 69x) DNA are included here as well as RNAseq data for 42 of the tumors. The study cohort was equally divided between patients who experienced pathological complete response and those with residual disease. Samples were obtained from the American College of Surgeons Oncology Group Z1041 trial (NCT00513292) and a local single-institution study (NCT00353483).]]>
Case selection: 37 cases were accessed from the American College of Surgeons Oncology Group Z1041 trial (NCT00513292) that compared the pathological complete response (pCR) rate of patients with HER2-positive breast cancer who received a sequential regimen of concurrent weekly paclitaxel and trastuzumab followed by continued weekly trastuzumab administered concurrently with fluorouracil, epirubicin, and cyclophosphamide (FEC-75) to the pCR rate of a sequential regimen of FEC-75 alone followed by concurrent weekly paclitaxel and trastuzumab. An additional 11 HER2-positive included breast cancer cases were enrolled in a local trial at Washington University School of Medicine (NCT00353483) and received neoadjuvant treatment with trastuzumab in combination with other chemotherapies. All cases were females with invasive breast cancer, not pregnant, and >= 18 years of age. All cases were identified as HER2-positive by IHC and/or FISH. ]]>