P5-13-22: Gene Expression Profiles Predict Pathological Complete Response to Standard Neoadjuvant Fluorouracil, Doxorubicin, and Cyclophosphamide and Paclitaxel with or without Trastuzumab in Early Breast Cancer.

Abstract

Abstract Background To examine the feasibility of gene expression signature as a predictor of pathological complete response (pCR) to sequential fluorouracil, doxorubicin, and cyclophosphamide (FEC) and weekly paclitaxel (P) with or without trastuzumab (T) neoadjuvant chemotherapy. Materials and Methods: We have conducted consecutive two prospective phase II, establishing training and validation sets, with similar eligible criteria include, stage IIA-IIIC, chemotherapy-naïve, measurable disease, age ≥ 20, PS 0/1, and adequate organ function. Patients were treated preoperatively with 4 cycles of FEC (500/100/500 mg/m2) followed by 12 cycles of weekly P (80 mg/m2) with or without T (2mg/kg). Patients underwent pretreatment fine-needle biopsy for cDNA microarray using Affimetrix Gene Chip U133 plus 2.0 arrays with 30,000 differential expressions of various genes. We ranked gene probes from training sets according to a predictive power concerning pCR by Wilcoxon, and validated them using validation sets by SVM. Results: Between July 2007 and December 2010, 122 patients were enrolled in the two consecutive prospective studies (training: 89 pts, validation: 33 pts). Median age was 51. PS 0/1: 115/7; Stage IIA/IIB/IIIA/IIIB/IIIC: 30/57/20/14/1; Histological subtype: ER+HER2− (LA) / ER+HER2+ (LB) / ER-HER2− (TN) / ER-HER2+ (enrich-HER): 51/18/24/29. All patients have received curable operations. pCR rate was 31.1% (LA; 2.0%, LB; 44.4%, TN; 37.5%, enrich-HER; 69.0%). 104 (85.2%) sufficient mRNA for cDNA microarray from individual primary breast cancer tissues fine-needle biopsy are available. As reported previously, the breast cancers were classified into a Luminal A/B, Basal-like, HER2−enriched, Claudin-low intrinsic subtypes, indicating a high quality of the representative method. In HER2 positive breast cancer, HER2−enriched subtype was a reproductive predictive marker. In contrast, In HER2 negative breast cancer, three genes (N-myc and STAT interacter, Tryptophanyl-tRNA synthetase, and IQCE) and basal-like subtype were validated as the predictors of pCR. The three genes were also identified as predictors of pCR in the triple negative population. Conclusions: Specific gene expression profiles predict pCR to standard neoadjuvant regimen, especially in triple negative breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-13-22.