Abstract P3-07-24: The role of glucocorticoid receptor (GR) expression in predicting pathological complete response (pCR) to neoadjuvant chemotherapy in triple-negative breast cancer (TNBC)

Abstract

Abstract Background Up to 40% of breast cancers have moderate to strong expression of GR, and activation of GR is associated with poor prognosis in ER-negative breast cancer. GR activation in breast cancer cells initiates anti-apoptotic signaling, contributing to chemotherapy resistance. We hypothesize that GR highly expressing TNBCs will have a suboptimal response to neoadjuvant chemotherapy. Methods We identified patients with triple-negative breast cancer (TNBC) who received neoadjuvant chemotherapy at the University of Chicago between 2002 and 2014 under IRB approved protocols. Those patients for whom pre-treatment and post-treatment tissue was available were included in this study. Unstained sections of formalin-fixed paraffin-embedded primary tumor were obtained. Percentage tumor cell GR expression was determined via immunohistochemical (IHC) examination using two different antibodies: the anti-GR rabbit monoclonal XP antibody (Cell Signaling, D8H2, 1:500 dilution) and the polyclonal rabbit anti-GR antibody (1:80). Staining was performed according to methods previously published by Belova et al. TNBCs were considered GR positive if greater than 10% of cancer cells stained moderately to strongly positive for GR. Results Fifty paired tissue samples were identified and pre- and post-treatment tissue was stained for GR using two anti-GR antibodies as above. Of these 50 cases, 80% had moderate to strong expression of GR using the XP antibody; results with the polyclonal ab will be compared. Percentage GR expression did not change in the setting of treatment. Work to correlate GR expression using the monoclonal versus the polyclonal antibody and clinicopathological features is ongoing. Conclusions To our knowledge, this is the first study attempting to evaluate percentage GR expression as a biomarker of response to neoadjuvant chemotherapy in TNBC. If higher GR expression correlates with a lower pCR rate in TNBC as hypothesized, then GR blockade in conjunction with chemotherapy may overcome chemotherapy resistance and lead to improved response to treatment in patients with GR expressing TNBCs. Citation Format: Saha P, Turk A, Lurain K, Baker G, Conzen S, Nanda R. The role of glucocorticoid receptor (GR) expression in predicting pathological complete response (pCR) to neoadjuvant chemotherapy in triple-negative breast cancer (TNBC). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-24.