ERB-B4 After Treatment With HDAC Inhibitor in ER+ Tamoxifen Refractory Breast Cancer

The long-term objective of this research is to understand the molecular mechanisms of
acquired endocrine resistance in breast cancer. Identifying these mechanisms is critical to
the implementation of novel therapeutic strategies that can target and overcome altered gene
networks involved in controlling breast cancer progression. While patients with tumors over
expressing HER1, 2, or 3 have been shown to have reduced survival, patients with those
tumors which overexpressed HER4 (erbB4) had increased survival (Witton 2003).

This is a non-randomized, single-arm, proof of principle trial. Selected are patients with
advanced-stage breast cancer whose tumors are ER+, tamoxifen refractory. Histologically
proven diagnosis of recurrent or metastatic breast cancer is advanced cancer for which there
is no treatment available which would have a reasonable chance of cure. Treatment failure is
defined as tumor progression after chemotherapy and tamoxifen therapy. Patients will be
given five 30mg doses of HDAC inhibitor (LBH) over a period of two weeks. A dose will be
taken on Days 1,3,5,8 and 10. Patients will have a diagnostic tumor biopsy prior to drug
administration and a diagnostic biopsy within 48 hours (2 days) of the last dose. Primary
endpoints are measured by biopsy of palpable tumor with immunohistochemical staining for
ERBB4. Secondary end points include the evaluation of cell death, apoptosis, with
immunohistochemical staining for DNA breaks by TUNEL assay.