A significant increase in the use of neoadjuvant chemotherapy over time was identified, and treatment with mastectomy as definitive surgical management remained high. There was significant variability in neoadjuvant chemotherapy use by the operating surgeons, in addition to factors generally associated with more locally advanced/aggressive tumors.
11057 Background: Personalized approaches to breast cancer therapy depend on genomic assays. While assays based on fixed tissues offer greater convenience, the spectrum of biology interrogated is limited. Full-transcriptome assays using microarrays are more challenging, but have the advantage of providing multiple prognostic and predictive signatures in one assay. We have created a clinical infrastructure with the objective of obtaining full genome expression data on breast cancer samples as a clinical assay for use in a prospective trial. Methods: “Performance of Genomic Expression Profiles to Direct the Use of Preoperative Chemotherapy for Early Stage Breast Cancer” is a prospective trial validating genomic signatures for predicting response to doxorubicin (A) or docetaxel (T) treatment in HER2 negative cancers. Fresh-frozen cores are reviewed by the study pathologist for tumor content. RNA is then extracted and probe generated to hybrize to an Affymetrix U133Plus2.0 microarray. Microarray data quality is determined using summary metrics for U133Plus2.0 arrays and principal component analysis (PCA) plots. The data is then used for predicting A or T sensitivity. Results: Thirteen cancers have been analyzed in the context of the above trial. Histologic type was lobular for 1, and predominantly ductal for 12 (10 ER positive, 3 ER negative). Median tumor size was 3.4 cm (range, 1.8–5.7). Microarray analysis was successful on 11 tumors (84%), providing data of sufficient quality to make predictions of A and T sensitivity. One sample hybridization failed QC as detected by PCA analysis, and one sample had insufficient RNA. The median “tissue to array data” time and “study consent to initiation of treatment” time were 5 days (range, 3–8) and 14 days (range, 11–36), respectively. Conclusions: Our initial experience shows that full-genome expression analysis on frozen tumor using an Affymetrix platform is feasible as a clinical assay for breast cancer. The resulting data is being used in a prospective marker validation protocol for predicting chemosensitivity. The data can also be analyzed for a variety of other potential prognostic and predictive signatures for guiding therapy. No significant financial relationships to disclose.
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