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AUSTIN, Texas -- The profound bone loss often experienced by women with early-stage breast cancer on ovarian function suppression and aromatase inhibitor (AI) therapy to prevent cancer recurrence appeared to be prevented with denosumab (Prolia) every 6 months, a randomized controlled trial showed.

After 12 months, the drug increased areal bone mineral density (BMD) by about 2% among women taking estradiol suppression treatments compared with a decrease of 8% in those assigned to placebo (P<0.001), reported Sabashini Ramchand, MBBS, of the University of Melbourne in Australia, at the annual meeting of the American Society for Bone and Mineral Research.

"Women diagnosed with estrogen receptor-positive early-stage breast cancer have a near-normal life expectancy; but in those women at high risk of recurrence, concurrent ovarian function suppression and aromatase inhibition offers improved cancer outcomes compared with tamoxifen monotherapy," said Ramchand.

However, she also noted that profound bone loss and increased risk of osteoporosis are side effects of the treatments. "Given the anticipated longevity of these patients, denosumab is likely to be beneficial when given at the time of commencing maximal estradiol depletion therapy," Ramchand suggested.

Femoral neck areal BMD increased by about 2% over 12 months in patients who got an injection of denosumab at baseline and a second at 6 months, while the areal BMD at the femoral neck decreased by about 5% among women on placebo (P<0.001).

The story was similar when areal BMD was measured at the hip, with about a 1% gain in areal BMD on denosumab compared with a 5% decrease on placebo (P<0.001).

Volumetric BMD measured at the tibia also showed a benefit with denosumab therapy, with no change in volumetric BMD compared with a loss of 6% among women in the placebo arm of the study (P<0.001).

Ramchand acknowledged that the short time frame of the study and the low numbers of patients (N=68) left the study underpowered to assess whether treatment with denosumab made a difference in the likelihood of fractures.

"Denosumab obviously seems to work in preventing bone mineral density loss," said session co-moderator Rodrigo Valderrabano, MD, of Brigham and Women's Hospital and Harvard Medical School in Boston. "But there have been other studies that also show that zoledronic acid [Reclast, Zometa] also works well to prevent bone loss in this population, and that zoledronic acid also may have other benefits in preventing cancer recurrence."

"This study does show that denosumab could be an alternative agent in this population, but at this point, I would not say that denosumab would be the preferred agent. It is good to have this clean data that shows that denosumab works well in this population," he told 名媛直播.

Denosumab, a RANK ligand inhibitor, is for increasing bone mass in women with breast cancer at high risk for fracture receiving adjuvant AIs, among other indications.

"The bone density losses with ovarian suppression therapy are immense, so even without fracture information, there is still good reason to put women on these therapies to combat bone loss," said Valderrabano.

In the study, the research team enrolled women undergoing estradiol suppression regimens and assigned 34 to receive denosumab and 34 to receive placebo. To be eligible for the study, women had to be premenopausal and begin assigned therapy within 12 weeks of commencing ovarian function suppression.

The study excluded women who were already at risk of osteoporosis, had pre-existing minimal fractures, had diabetes, and those who were pregnant or breastfeeding. Serum biochemistry was analyzed every 3 months, and other bone health measures were taken at baseline, 6 months, and at the end of the 12-month study.

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