A Phase II Randomized Trial of Neoadjuvant Trastuzumab or Lapatinib or the Combination of Trastuzumab and Lapatinib, Followed by Docetaxel and Carboplatin with Trastuzumab and/or Lapatinib in Patients with HER2+ Breast Cancer [Baseline]

Adjuvant docetaxel, carboplatin, and trastuzumab (TCH) is a standard regimen for HER2+ breast cancer. Dual HER2-blockade with lapatinib (L) and trastuzumab demonstrated significant activity in the metastatic and neoadjuvant settings. This study evaluates neoadjuvant TC plus trastuzumab (H) and/or lapatinib (L). This study demonstrated a similar pCR rate with TCH and TCHL and a lower rate of pCR with TCL. Treatment-related toxicity limited the ability for participants to receive protocol-specified chemotherapy and HER2-targeted therapy in the TCHL Arm. Microarray experiments were conducted using the 2-color Agilent Whole Human Genome platform. Samples were collected before treatment at the time of diagnosis (baseline samples). Every adequate baseline sample was profiled against a breast tumor mixed reference pool. 110 patients had baseline samples which passed QC. Samples were also taken after two weeks of treatment with the HER2-targeted biologic. (run-in samples). Each run-in sample was compared to the baseline sample from the same patient. 89 patients had adequate baseline and run-in samples. The Agilent feature extracted data was processed using the Rosetta Resolver Gene Expression system V 7.2.0 SP2.12. Data is available for each unique probe on the Agilent platform (total of 41000) and expressed as log 10 ratio of experimental to reference sample. In the 110 baseline experiments the reference sample is the untreated breast tumor collected at diagnosis and the reference sample is the mixed breast tumor reference. In the 89 run-in experiments, the experimental sample is the run-in sample taken after two weeks of treatment and the reference sample is the baseline sample taken at diagnosis from the same patient. NOTE: the assigned treatment group and the final drug response is provided as sample characteristics; T=Docetaxel C=Carboplatin, H=trastuzumab, Ty=lapatinib, RD=residual disease, PCR=Pathological complete Response defined as the absence of invasive cancer in the breast and axilla