Abstract P1-07-07: Inflammatory gene expression variations in the interval between core needle biopsy and excisional biopsy in early breast cancer
Authors: Jeselsohn RM , Regan MM , Werner L , Fatima A , He HH , Brown M , Iglehart JD , Richardson AL , Come S 
Published: August 2014

Abstract
Introduction: Advancements in molecular biology have unveiled multiple breast cancer promoting pathways and potential therapeutic targets. Large randomized clinical trials remain the ultimate means of validating therapeutic efficacy, but they require large cohorts of patients and are lengthy and costly. An alternative approach is to conduct a window of opportunity study in which patients are exposed to a drug pre-surgically during the interval between the core needle biopsy (CNB) and the definitive surgery (excisional biopsy (EB)). These are non-therapeutic studies and the end point is not clinical or pathological response but rather evaluation of molecular changes in the tumor specimens that can predict response. However, since the end points of the non-therapeutic studies are biologic, it is critical to first define any biologic changes that occur in the absence of treatment. In this study, we compared the molecular profiles of breast cancer tumors at the time of the diagnostic biopsy versus the definitive surgery in the absence of any intervention.
Methods: The study was conducted with DFCI/HCC IRB approval and patient consent. Post-menopausal women with a breast lesion suspected to be cancerous were eligible for this study. We obtained a tissue specimen at the time of a CNB and if determined to be consistent with invasive carcinoma a second specimen was obtained at the time of the EB. We used the Nanostring Ncounter system to study the expression level of 148 transcripts. Since we expected that most of the tumors will be hormone receptor positive (HR+), the library included; genes that have been shown to be prognostic in HR+ tumors (Oncotype DX®, PAM50), estrogen receptor (ER) modulators, ER responsive genes and inflammatory genes. The Wilcoxon's signed rank test was used to evaluate for changes in gene expression levels between the paired samples.
Results: 25 patients were enrolled in this study and paired tumor tissue samples were obtained from all patients. 21 of the paired samples were successfully analyzed by the nanostring system. 86% of the patients are HR+/Her2−. We found that the gene expression levels of 14 out of the 148 genes (9%) did change between the CNB and EB without any intervention (p &lt; 0.05). 8 of these 14 genes can be classified as inflammatory genes that also have known functions in tumor progression. The expression of these 8 genes was upregulated between the biopsies and include; CD68, ADM, CD14, IL6, VEGFA, CD52, CD44 and SNAI1. These changes may be due to an inflammatory response to the CNB. Ki67 expression did not change significantly between biopsies.
Conclusions: In this study we found significant gene expression variations between CNBs and EBs in 9% of the genes tested, without any therapeutic intervention. Our findings suggest that when conducting a “Window of Opportunity” clinical study to evaluate for biomarkers of response or resistance, changes in expression of inflammatory genes cannot be attributed to treatment and a control arm should be considered.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-07-07.