Abstract PD07-06: Basal-Like Molecular Subtype Predicts Response to Neoadjuvant Chemotherapy with Epirubicine, Cyclophosphamide, and Docetaxel in Patients with Primary Breast Cancer

Abstract

Abstract Background: Gene expression profiling provides an opportunity to predict response to specific regimens of neo-adjuvant chemotherapy (NAC) in breast cancer patients. Materials and Methods: In a prospective cohort study of 32 women with primary invasive breast cancer with a measurable lesion, we obtained a tumor specimen by high speed core biopsy before and after 4 cycles of NAC with epirubicine 90mg/m2 and cyclophosphamide 600mg/m2 every 3 weeks, followed by 4 cycles of docetaxel 100mg/m2. Total RNA was extracted from tumor specimens and the whole transcriptome was quantified with Agilent's 44K single color microarray interrogating 44000 unique human genes. Tumor lesions were ultrasonographically measured to assess response using Sinn criteria. Data analysis was performed by GeneSpring v11 and IBM SPSS v18. Results: Using three single sample predictors, 10 tumors were classified as basal-like and 22 tumors were classified as non basal-like. We found that gene expression-based molecular subtype (basal-like vs. non basal-like) (p=0.003), but not tumor grade (p=0.07), estrogen receptor (p=0.1), progesterone receptor (p=0.6), and HER2 status (p=0.4) predicted response to NAC. Specifically, 7/10 basal-like tumors responded to NAC, whereas 19/22 non basal-like tumors did not respond. Comparing gene expression signatures before and after 4 cycles of NAC, we found that all patients with an initial non basal-like tumor retained this tumor type, whereas 5/7 basal-like tumors, including all responders, lost this molecular subtype. Using regression models based on centroid predicition gene sets, complete prediction of response to NAC based on the initial tumor biopsy as well as on the change of gene expression between two tumor biopsies was achieved with a 21 gene list (p=0.000008) and a 23 gene list (p=0.000007), respectively. Of note, both the expression and upregulation of a single gene, ie HER4, predicted response to NAC in 26/32 (81%; p=0.002) and in 23/25 (92%; P<0.001) patients, respectively. Conclusions: Basal-like molecular subtype and therapy-induced HER4 gene upregulation predict response to NAC with epirubicine, cyclophosphamide, and docetaxel. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD07-06.