A recently published study in The New England Journal of Medicine (360:679-691, 2009) shows that in premenopausal women with early breast cancer, administering zoledronic acid(Drug information on zoledronic acid) (Zometa) along with postsurgical hormone therapy provided a reduction in risk of recurrence or death that was 36% beyond that achieved with hormone therapy alone.
The study, from the Austrian Breast and Colorectal Cancer Study Group (ABCSG), is the first large, randomized, phase III clinical trial to show that zoledronic acid offers significant protection against the return of early breast cancer in premenopausal women. Prior laboratory research suggested that zoledronic acid might have direct anticancer effects, including helping to protect against the return and spread of cancer before it reaches an advanced stage.
“The possible return of breast cancer is a major concern among women who’ve undergone surgery to remove their tumors. We anticipate that this publication in The New England Journal of Medicine will provide oncologists with evidence regarding an additional treatment regimen to further help reduce the risk of breast cancer recurrence, or even death, for premenopausal women with hormonesensitive breast cancer,” said lead investigator Michael Gnant, md, of the Medical University of Vienna.
Four Study Groups
The ABCSG trial (ABCSG-12) enrolled 1,803 premenopausal women with estrogen receptor–positive stage I or II breast cancer, with fewer than 10 axillary lymph nodes involved. Patients were recruited for the study after curative surgery and initiation of goserelin(Drug information on goserelin) (Zoladex) treatment for ovarian suppression, and randomly assigned into one of four study groups: (1) anastrozole(Drug information on anastrozole) (Arimidex) plus zoledronic acid; (2) anastrozole alone; (3) tamoxifen(Drug information on tamoxifen) plus zoledronic acid; (4) tamoxifen alone. The treatment period was 3 years, and the median follow-up was 48 months.
At 48 months, disease-free survival events were reduced by 36% (P = .01), and the risk of recurrence-free survival events fell by 35% (P = .02) with zoledronic acid added to hormone therapy vs hormone therapy alone. A total of 16 deaths had occurred among patients who received zoledronic acid with hormone therapy vs 26 deaths in patients who received hormone therapy alone, which resulted in a nonsignificant reduction in the risk of death in patients who received zoledronic acid compared with those who received hormone therapy alone (P = .11). A similar trend was noted toward a reduction in bone metastases among patients who received zoledronic acid compared with those who received hormone therapy alone (P = .22).
Longer follow-up and a larger number of events will be necessary to determine if any significant differences exist between the groups for overall survival and bone metastasis-free survival. Overall, treatment was generally well-tolerated and side effects were consistent with known drug safety profile.