SABCS 2011: Zoledronic Acid Shows Long-Term Benefit in Survivorship for Premenopausal ER-Positive Breast Cancer
Zoledronic acid and endocrine treatment improved both disease-free and overall survival in early-stage, premenopausal ER-positive breast cancer, according to study results presented at the 34th Annual CTRC-AACR San Antonio Breast Cancer Symposium. Researchers from the Austrian Breast & Colorectal Cancer Study Group (ABCSG-12) presented their results after a median of 76 months of follow-up, confirming those reported at 48 and 62 months.
1,803 premenopausal women with ER-positive early-stage breast cancer were randomized to one of the four-arms: tamoxifen or anastrozole or each of these two treatments with zoledronic acid for three years. The primary endpoints were disease-free survival (DFS) and overall survival (OS).
After a median follow-up of 76 months, patients receiving zoledronic acid had a 27% reduction in the risk of DFS events (HR=0.73) and a 41% reduction in the risk of death (HR=0.59) compared to patients receiving solely tamoxifen or anastrozole. This risk reduction did not vary based on if the patient received tamoxifen or anastrozole, but did depend on patient age. Among the 1,390 patients >40 years of age with presumed complete ovarian blockade (low estrogen environment), zoledronic acid reduced the risk of DFS events by 34% and the risk of death by 49%. There were no significant DFS or OS benefits in patients less than 40 years old. “These results are consistent with the significant DFS and OS improvements seen in the postmenopausal cohort of the AZURE trial and suggest that both estrogen deprivation and reduction of bone-turnover–derived growth factors in the bone marrow microenvironment are needed for sufficient suppression of dormant micrometastases.”
Another study, the Zometa-Femara Adjuvant Synergy Trial (ZO-FAST), which was also presented at the 34th Annual CTRC-AACR San Antonio Breast Cancer Symposium, suggests that women five years postmenopause had the greatest benefit from zoledronic acid. In this randomized trial of 1,065 patients with early hormone receptor-positive breast cancer followed for 60 months, immediate treatment with zoledronic acid increased bone mineral density and reduced the risk of disease recurrence. Additionally, even delayed treatment with the bisphosphonate improved disease outcomes compared to women who never started the treatment.