New Weapon in Preventing Bone Loss in Patients Undergoing Treatment for Breast Cancer

Women with breast cancer have a new ally in their fight, as researchers now believe zoledronic acid will help prevent bone loss associated with adjuvant aromatase inhibitor therapy. The latest results from the Z-FAST trial were published in Cancer by Dr Adam M. Brufsky, professor of medicine at the University of Pittsburgh School of Medicine and associate director of clinical investigation for the University of Pittsburgh Cancer Institute, and colleagues.

The Z-FAST was a 5-year, open-label, randomized multicenter study that followed postmenopausal women with a history of surgically resectable, early stage (I, II, or IIIa), estrogen receptor-positive and/or progesterone receptor-positive breast cancer. Patients (N=602) received 2.5 mg letrozole (orally and daily for 5 years); they were randomly assigned to groups who immediately received 4 mg zoledronic acid (intravenously) every 6 months and those who received zoledronic acid at 36 month follow-up based on newly diagnosed bone mineral density issues. Serum bone-specific alkaline phosphatase (BSAP) concentrations were measured at baseline and then periodically throughout the study.

Brufsky and colleagues found that patients who received zoledronic acid at study initiation had increased lumbar spine and total hip bone mineral density throughout the study, while those who had a delayed start of zoledronic acid displayed consistent bone mineral density decreases throughout the study. Specifically, for the percentage of change in lumbar spine bone mineral density, the study authors found the least squares mean difference between groups steadily increased from baseline at 4.3% to 8.9% at month 61. In addition, by month 61, the researchers found that fractures occurred slightly more often among the group who received delayed zoledronic acid as compared to those patients who received it immediately (11% and 9.3%, respectively; the difference was not found to be statistically significant.

However, good news was also seen in the group who had delayed drug administration. In their post hoc analysis, the researchers found that patients in the delayed-start group who received zoledronic acid by month 60 experienced 4% increase in lumbar spine bone mineral density at study end as compared to baseline. In fact, Brufsky et al. also noted that the rate of bone mineral density declined over time in the delayed group; the researchers hypothesized this decline may be due to the fact that majority of the patients in the delayed group (66%) eventually met criteria for receiving zoledronic acid.

The researchers found a relatively good safety profile for zoledronic acid use. The researchers found that adverse events (both types and rates) were similar among the groups. Most of the events were grades 1 or 2. Furthermore, the drug seemed to improve survival in breast cancer patients, as disease recurrence and death rate at month 12 was lower among the group who immediately received zoledronic acid as compared to those who did not. However, the study authors caution that this finding needs to be confirmed in further research.

Administered alone or after tamoxifen in postmenopausal women with early breast cancer, adjuvant aromatase inhibitor therapy has been linked to progressive bone loss and increased fracture risk. It is believed that zoledronic acid may inhibit estrogen deprivation-associated osteoclast-mediated bone resorption.

“Upfront zoledronic acid seems to be the preferred treatment strategy versus delayed administration,” Brufsky et al. concluded, “as it significantly and progressively increases BMD [bone mineral density] in postmenopausal women with early BC [breast cancer] receiving letrozole for 5 years.” They added, “Long-term coadministration of letrozole and zoledronic acid is well tolerated.”

Related Content:Metastatic Breast Cancer Treatment Guidelines Updated

References:

Reference:
Brufsky AM, Harker WG, Beck JT, et al. Final 5-year results of Z-FAST trial: adjuvant zoledronic acid maintains bone mass in postmenopausal breast cancer patients receiving letrozole. Cancer. 2011; Oct 10 [Epub].