Osteoporosis drug may have clinical activity in breast cancer

Issue: August 10, 2013

A drug approved for use in osteoporosis in Europe demonstrated inhibitive properties in breast cancer cells, according to study results.

Perspective from Edith A. Perez, MD

Researchers constructed predictive models to determine which selective estrogen receptor modulators (SERMs) may have clinical utility in advanced breast cancer. Specifically, they evaluated whether the drugs might affect ER-alpha conformation and induce different gene expression profiles in relevant cell model systems.

Results indicated that bazedoxifene (Pfizer) was the drug most similar to ICI 182,780 (fulvestrant; Faslodex, AstraZeneca). Further analysis indicated that bazedoxifene inhibited growth in tamoxifen-sensitive and tamoxifen-resistant breast tumor xenografts.

The study drug also was linked to induction of a unique conformational change in ER-alpha structure. The result of that change is a proteasome-dependent degradation in cellular and xenograft models of breast cancer.

Moreover, competitive antagonism by the drug blocked ER-alpha transactivation and the proliferation of breast cancer cells.

“Based on the results of these studies, we conclude that [bazedoxifene] or other SERMs that exhibit the pharmacological properties of a pure antagonist may be effective in the treatment and prevention of breast cancer,” the researchers concluded.

For more information:

Wardell SE. #SAT-297. Presented at: The Endocrine Society Annual Meeting and Expo; June 15-18, 2013; San Francisco.

Disclosure: Wardell reports a consulting role with Pfizer Global R&D.

Perspective

Edith A. Perez, MD

The estrogen receptor was the first identified target against breast cancer more than 40 years ago, but we still do not have the ability to totally prevent or cure ER-positive breast cancer. Thousands, if not millions, of reports have been published in the medical literature addressing ER blockers, potential mechanisms of resistance to anti-estrogens, and ideas to improve current therapeutic options. The report of preclinical activity of novel SERM bazedoxifene merits follow-up as a potential anticancer agent in the clinic. This will be somewhat easier if there is a sufficient safety profile, as the drug is under evaluation for osteoporosis. The challenging questions are: 1) Is the activity different enough to potentially be better than raloxifene or fulvestrant from the clinical and regulatory standpoints? 2) Will it be worthwhile to continue putting emphasis on modulation of existing SERMs or should resources be placed on combination strategies adding blockers of other signaling proteins relevant to the pathophysiology of breast cancer? Only time will tell.

Edith A. Perez, MD

HemOnc Today Editorial Board member

Disclosures: Perez reports no relevant financial disclosures.