Abstract
1015 Background: Arzoxifene (LY353381.HCl) is a new selective estrogen receptor modulator, SERM, with strong breast antiestrogen activity and absence of uterine agonist activity that is being explored as a potential breast cancer chemoprevention agent. We performed a multi-institutional Phase IB evaluation of the effects of arzoxifene on serum and tissue biomarkers in women with newly diagnosed DCIS and T1/T2 invasive cancer who received study agent in the interval between core biopsy and definitive re-excision. Methods: Post-menopausal women were randomized (2:1) to 20 mg of arzoxifene daily vs. matched placebo. Women discontinued hormone replacement therapy (HRT) prior to entry on study. Tissue from biopsy and re-excision specimens was evaluated immunohistochemically for proliferation (Ki-67 by MIB-1; PCNA) and other biomarkers potentially related to drug effect. Only subjects with an ER+ and/or PR+ tumor at biopsy, with tumor tissue available from both biopsy and re-excision, were evaluated for biomarker modulation. Results: 74 subjects entered the study. For 58 subjects evaluable for tissue biomarker analysis, a change in ER expression (median decrease of 6% positive cells) was observed for subjects receiving arzoxifene, that was statistically significant (p=0.0068) compared to the placebo group (median change = 0%). However, the changes in proliferation indices (median decreases: Ki-67 = 1.5%, PCNA = 3%) were not statistically different from the placebo group (median decreases: Ki-67 = 1.1%, PCNA = 0%). This may be due to the large number (46%) of subjects who discontinued HRT in the peri-biopsy period, resulting in decreases in proliferation independent of an arzoxifene effect. Conclusions: We have demonstrated the feasibility of accrual to a multi-institutional biomarker modulation trial utilizing women with newly-diagnosed breast cancer. Given a favorable side effect profile and the modulations of tissue (ER and proliferation) biomarkers associated with risk of breast cancer development, arzoxifene remains a candidate for continued evaluation as a breast cancer chemoprevention agent. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration NCI
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call