Molecular Signature of Valproic Acid in Breast Cancer With Functional Imaging Assessment - a Pilot
Status:
Terminated
Trial end date:
2015-05-01
Target enrollment:
Participant gender:
Summary
The investigators' hypothesis is that valproic acid given before surgery for newly diagnosed
breast cancer will increase breast tumor histone acetylation at tolerable doses and that the
increase in breast tumor histone acetylation will correlate with valproic acid blood levels
and changes in peripheral blood white blood cell histone acetylation. Published in vitro
studies have shown sensitivity of breast cancer cells to histone deacetylase inhibitors
(Fortunati et al., 2008; Fuino et al., 2003; Hodges-Gallagher et al., 2007; Olsen et al.,
2004). The investigators' gene array data predict sensitivity to valproic acid in over half
of breast cancers [Bild, unpublished]. The investigators hypothesize that in women with newly
diagnosed breast cancers valproic acid will have an unacceptable toxicity rate less than 15%
at doses that increase tumor histone acetylation and that valproic acid will decrease the
Ki-67 in at least half of breast tumors by over 20%. The investigators also hypothesize that
their genomically-derived signature for sensitivity to valproic acid (GDSS-VPA) can be used
to predict which tumors will have a decrease proliferation as measured by Ki-67 by at least
20%. The investigators hypothesize that valproic acid levels and histone acetylation levels
in peripheral leukocytes will correlate with a decrease in the Ki-67 proliferation index by
20%. The investigators hypothesize that DCE-MRI imaging studies will provide an accurate and
quantitative means of assessing tumor response to valproic acid. Finally, the investigators
hypothesize that response to valproic acid will not be affected by intrinsic breast cancer
subtype.