Abstract
657 Background: Recent trials have demonstrated remarkable efficacy from combined trastuzumab and chemotherapy in the adjuvant setting of breast cancer. However, trastuzumab resistance continues to be problematic. We intended to explore the possibility of the presence of a gene expression signature for trastuzumab resistance. Methods: Forty-one consecutive breast carcinoma cases that had amplified HER2 and fresh frozen tissue available were collected. Twelve patients were treated with trastuzumab, 3 of which had recurrence. Eleven patients were not treated with trastuzumab, 6 of which had recurrence. Human genome-wide Illumina bead microarrays were used to identify differentially expressed genes (DEGs) for nonrecurrence versus recurrence in trastuzumab treated (TT) patients, and in trastuzumab nontreated (TNT) patients, respectively. Microarrays were also used to identify DEGs from separate comparisons involving collected patients' clinicopathologic data (age, race, tumor stage, hormonal status, and menopausal status). Results: TheDEGs for nonrecurrence versus recurrence in the TT group were distinct from those for nonrecurrence versus recurrence in the TNT group. They were also distinct from the DEGs obtained from comparisons involving other collected patients' clinicopathologic data. While DEGs in the TT group were enriched in the DNA binding, those in the TNT group are enriched in immunity and defense. The HER2 pathway was found to be significantly disregulated only in the TT group. None of the known genes that have been described to be involved in trastuzumab resistance showed any significant changes at transcriptional level. Conclusions: Differential expression of key genes indentified in this study might offer an insight into a possible mechanism of trastuzumab resistance in breast carcinoma, and might emerge as potential biomarkers for diagnosis and treatment of trastuzumab resistance. No significant financial relationships to disclose.
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