Abstract
Drug resistance in breast cancer is a major obstacle to successful chemotherapy. In this study we used cDNA microarray technology to examine gene expression profiles obtained from fine needle aspiration (FNA) of primary breast tumors before and after systemic chemotherapy. Our goal was to determine the feasibility of obtaining representative expression array profiles from limited amounts of tissue and to identify those expression profiles that correlate with treatment response. Repeat presurgical FNA samples were taken from six patients who were to undergo primary surgical treatment. Additionally, a group of 10 patients who were to receive neoadjuvant chemotherapy underwent two FNAs before chemotherapy (adriamycin 60 mg/m2 and cyclophosphamide 600 mg/m2) followed by another FNA on day 21 after the first cycle. Total RNA was amplified with T7 Eberwine's procedure and labeled cDNA was hybridized onto a 7600-feature glass cDNA microarray. We identified candidate gene expression profiles that might distinguish tumors with complete response to chemotherapy from tumors that do not respond, and found that the number of genes that change after one cycle of chemotherapy was 10 times greater in the responding group than in the non-responding group. This study supports the suitability of FNA-derived cDNA microarray expression profiling of breast cancers as a comprehensive genomic approach for studying the mechanisms of drug resistance. Our findings also demonstrate the potential of monitoring post-chemotherapy changes in expression profiles as a measure of pharmacodynamic effect and suggests that these approaches might yield useful results when validated by larger studies.
Highlights
Chemotherapy given as adjuvant therapy after surgery to patients with primary operable breast cancer reduces the subsequent risk of relapse and death [1]
Pretreatment gene expression profiles are associated with response or lack of response to chemotherapy in breast carcinoma To assess whether cDNA microarray profiles obtained from fine needle aspiration (FNA) before chemotherapy would be able to differentiate and associate with the response or non-response to treatment, we studied an additional group of 10 patients with breast cancer who were to receive neoadjuvant chemotherapy
This study is the first to test the feasibility of obtaining representative array profiles from FNAs of breast carcinomas in a clinical setting
Summary
Chemotherapy given as adjuvant therapy after surgery to patients with primary operable breast cancer reduces the subsequent risk of relapse and death [1]. The absolute reduction in mortality is only about 10–12%, most patients receive adjuvant chemotherapy because it is not possible to identify, at the start of treatment, which patients might gain benefit The development of cDNA microarray technology has provided such an opportunity With this technology it has been possible to identify new classes in breast cancer according to their gene expression patterns and to correlate them with distinct clinical outcomes [5,6]. In this study we used cDNA microarray technology to examine gene expression profiles obtained from fine needle aspiration (FNA) of primary breast tumors before and after systemic chemotherapy. Conclusion: This study supports the suitability of FNA-derived cDNA microarray expression profiling of breast cancers as a comprehensive genomic approach for studying the mechanisms of drug resistance. Our findings demonstrate the potential of monitoring post-chemotherapy changes in expression profiles as a measure of pharmacodynamic effect and suggests that these approaches might yield useful results when validated by larger studies
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