Abstract 1843: Surgical and chemotherapy influence on circulating developmental microRNA miR17-92 and long term survival in breast and ovarian cancer patients.

Abstract

Background Breast cancer (BrCa) is treated with surgery (SUR), radiation (RAD) and or chemotherapy (CTx) based on stage at diagnosis. Over 75% of women are diagnosed with ovarian cancer (OvCa) are diagnosed at stage III and treated with debulking SUR and CTx. Only 1/5 of OvCa are cured of their disease with SUR followed by CTx. In stage III BrCa 40% are long term survivors after SUR, CTx & RAD. There are no markers to quantify the contribution of each therapeutic intervention to the overall success in cancer patients. Patterns of circulating miRs may explain the role of SUR and CTx in ovarian/breast cancer cure. MiRs-17-92 have essential roles in embryonal and immune system development. MiR-17-92 cluster is deleted in 20% of ovarian cancers. Aims We set out to identify changes microRNA patterns in plasma obtained before and after surgery for breast/ovarian cancer and during chemotherapy that correlated with the patients’ long-term outcomes. Methods Between 2004 and 2011 we investigated patterns of plasma miRNAs collected before, after surgery, during and after chemotherapy in 50 patients presenting for surgery for ovarian cancer 18 breast cancer patients and 11 age and race-matched normal controls. We also collected blood at ovarian cancer relapse and tumor and benign ovary for miRNA analysis. 2-sample t-test was used for all 2-sample comparison and ANOVA followed by Benjamin-Hochberg method for multiple testing to limit the false discovery rate (FDR) at the 5% level. All tests were 2-tailed and results with a p<0.05 were considered statistically significant. Results Fifty patients were operated for EOC mean age at surgery 65 (range 51-78), 11 race matched women controls - mean age of 58 (range 25-67). Four patients were cured, 21 patients died within 36 month of their diagnosis and 21 patients who survived long term not cured but continue to receive chemotherapy. 18 brCa patients were ER/PR/Her2- W(5), B(5) and ER/PR+ W(5) B(3). MiR-19a was pre-op in patients with short over all survival (p< 0.003). CTx increased miR-19a 38-fold compared to the pre-SUR levels (p<0.0002). CTx up-ed MiR-19b 38 fold (p<0.003). MiR-92 low in pre-SUR plasma increased 17-fold during CTx (p<0.003). MiR-25 low in pre-SUR plasma and increased 47-fold during CTx (p<0.002). Changes in miR-17-92 cluster were the most dramatic in patients with OvCa treated with SUR and CTx. Post-SUR miRs from 17-92 cluster increased post-SUR in BrCa. High pre-SUR miR17-92 pre-SUR & during CTx forecast good outcome. Conclusions During CTx, levels of miR-17-92 change dramatically compared to the pre-surgical levels. Shifts in microRNAs from the cluster 17-92 observed in the nadir phase of adjuvant chemotherapy for ovarian cancer patients correlate with long term outcomes. Breast and ovarian cancer patients with higher circulating miR-17-92 levels in pre-surgical plasma levels had better long-term survival. Citation Format: Iuliana Shapira, Annette Lee, Michaela Oswald, Janaki Parameswaran, Keith Sultan, Daniel Budman. Surgical and chemotherapy influence on circulating developmental microRNA miR17-92 and long term survival in breast and ovarian cancer patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1843. doi:10.1158/1538-7445.AM2013-1843

Exosomal miRNAs as cancer biomarkers and therapeutic targets

“…It is important to consider the possible influence cancer treatment could have on ex‐miRNA profiles. Although some reports have shown changes in miRNA profiles in response to surgery and chemotherapy (53, 54), these studies often involve circulating miRNAs and there are few studies that look specifically at ex‐miRNA profiles. In breast cancer patients, neoadjuvant therapy was shown to result in a greater than 2‐fold increase in circulating miR‐503.…”