A new osteoporosis drug hinders the growth of estrogen-sensitive cancer that has become resistant to treatment with tamoxifen, a study in mice shows. The results were presented at The Endocrine Society’s 95th Annual Meeting in San Francisco.
The medication, bazedoxifene, which is approved in Europe under the brand name Conbriza for the treatment and prevention of postmenopausal osteoporosis, also reduced estrogen activity and estrogen receptor levels in cultured human breast cancer cells, the study authors reported.
“Bazedoxifene, a known, safe drug approved in Europe, may present a near-term option as an effective therapy for breast cancer in patients who have relapsed during treatment with tamoxifen or aromatase inhibitors,” said Suzanne Wardell, PhD, the study’s principal investigator and a research scientist at Duke University, Durham, N.C.
About 70 percent of breast cancers are hormone sensitive, the National Cancer Institute estimates, meaning they need female hormones like estrogen to grow. In one-third to one-half of these patients, the cancer becomes resistant to medications that block either estrogen production or activity of the estrogen receptor, according to Wardell, who said, “These women then have few treatment options.”
Treatment options include systemic, or whole-body, chemotherapy or often-painful injections of an anti-estrogen drug, fulvestrant into the buttocks muscle.
The investigators reasoned that one or more drugs known as selective estrogen receptor modulators, or SERMs, might prove effective in treating breast tumors that have developed resistance to hormone blockers. Most SERMs have anti-estrogen effects on some tissues and estrogen-like effects on other tissues. The new SERM bazedoxifene stimulates the estrogen receptor in bone to retain bone mineral density but inhibits estrogen receptor activation in the breast and uterus, Wardell said.
Wardell’s team tested bazedoxifene in a study funded by the drug’s manufacturer, Pfizer. First, they applied standard molecular biology techniques to multiple models of human-derived breast cancer cell lines. The models included cancer cells that were resistant to tamoxifen, aromatase inhibitors and lapatinib, a drug used to treat aggressive HER2-positive breast cancer. In all models, bazedoxifene reportedly inhibited estrogen-induced gene expression and cell proliferation.
The researchers then transplanted the cultured breast tumors into immune-compromised mice. Wardell said that bazedoxifene “completely inhibited the estrogen receptor-dependent tumor growth,” not only in tumors that had never received tamoxifen treatment but also in those that were resistant to tamoxifen. The drug deterred tumor growth to a similar extent as reported for fulvestrant, she said.
The ideal next research step, according to Wardell, would be a clinical trial to evaluate the efficacy of bazedoxifene in patients with metastatic, hormone therapy-resistant breast cancer.
Pfizer has applied for U.S. Food and Drug Administration approval of bazedoxifene but only when combined with conjugated estrogens for treatment of postmenopausal symptoms and prevention of postmenopausal osteoporosis, she said.
The Endocrine Society