A phase 1 window of opportunity study of valproic acid (VPA) in breast cancer testing a gene expression biomarker.

1084Background: VPA has anti-cancer activity thought to be due to its ability to inhibit histone deacetylase. We have published a 200 gene mRNA signature, called GDSS-VPA, that predicts breast cancer sensitivity to VPA in vitro and in vivo. The Valproic Acid Signature Trial (VAST, NCT01007695) was a window of opportunity study to examine the tolerability of VPA and assess the ability of the GDSS-VPA to predict biologic changes in breast tumors. Methods: Women with histologically confirmed, untreated breast cancer with breast tumors over 1.5cm diameter were recruited. After a DCE-MRI and tumor biopsy from which RNA was isolated for the GDSS-VPA, women took VPA for 7-12 days starting at 15mg/kg PO BID and increasing as tolerated to a maximum of 25mg/kg PO BID. On the last day of VPA treatment, a DCE-MRI was done and serum VPA level was measured followed by definitive breast surgery or, if chemotherapy was planned, a breast biopsy. Tumor proliferation before and after VPA was assessed by Ki-67 immunohistoche...