SABCS: Zoledronic Acid Prevents Bone Loss during Endocrine Therapy

Charles Bankhead
SAN ANTONIO, Dec. 14 -- Premenopausal breast cancer patients receiving adjuvant endocrine therapy did not suffer the substantial bone loss typically seen with such treatment when they were also given zoledronic acid (Zometa), updated results from a randomized clinical trial showed. Patients given bisphosphonate therapy maintained baseline bone mineral density at three years and had a 4% improvement at five years, Michael Gnant, M.D., of the Medical University of Vienna in Austria, reported at the San Antonio Breast Cancer Symposium.
Fewer than half of patients regained normal bone status without bisphosphonate therapy, he said.
"Prevention of treatment-induced bone loss should be considered for premenopausal breast cancer patients receiving estrogen-reducing adjuvant therapies," said Dr. Gnant.
Postmenopausal breast cancer patients also showed benefit from bisphosphonate therapy, said Adam Brufsky, M.D., Ph.D., of the University of Pittsburgh, who reported results from long-term follow-up in another trial.
In that study, concurrent treatment with zoledronic acid resulted in a net gain in bone density during endocrine therapy, Dr. Brufsky said, and, in contrast, delaying the start of bisphosphonate therapy led to a loss in bone density.
Dr. Gnant reported five-year data from the Austrian Breast and Colorectal Cancer Study Group-12 trial, which showed a significant reduction in bone density at three years in patients who did not receive zoledronic acid with endocrine therapy (J Clin Oncol 2007; 25: 820-828).
The trial involved 1,801 premenopausal patients with endocrine-responsive breast cancer. The data presented here included results from a bone substudy involving 404 patients.
In the parent trial, patients received postoperative goserelin for 28 days and then were randomized to tamoxifen or anastrozole (Arimidex). In the bone substudy, patients were randomized to endocrine therapy alone (N=199) or with concomitant zoledronic acid (N=205) for three years. The bisphosphonate was administered intravenously twice a year.
Patients in the bone substudy had a total of 1,533 measurements of bone mineral density, involving the lumbar spine and trochanter.
The 36-month data showed that patients who did not receive zoledronic acid lost an average of 11.3% of their bone density. The loss was greater with goserelin plus anastrozole (14%). Five-year data showed that bone mineral density remained 6.3% below baseline without bisphosphonate therapy.
In contrast, patients treated with zoledronic acid maintained baseline BMD at three years (+0.3%, P=0.85) and had a 4% improvement at five years (+3.9%, P=0.02).
Dr. Brufsky reported 36-month data from the Zometa-Femara Adjuvant Synergy Trial (Z-FAST), which involved 602 postmenopausal breast cancer patients in the United States and Canada.
All patients received letrozole (Femara) 2.5 mg/day and were randomized to immediate or delayed treatment with zoledronic acid. In the delayed-treatment arm, patients did not start the bisphosphonate until the bone mineral density T-score declined to less than -2.0 or a fracture occurred. The primary endpoint was change in lumbar spine BMD.
By 36 months, 62 (20.7%) patients in the delayed-therapy arm had begun zoledronic acid. The median time to initiation of therapy was 11.5 months, and the mean was 13.5 months.
Patients who received upfront bisphosphonate therapy had a mean increase of 3.72% in lumbar spine BMD compared with a decline of 2.95% in the delayed-therapy group (P<0.0001). Total hip BMD improved by 1.66% from baseline with upfront zoledronic acid versus a loss of 3.51% in the delayed-therapy group (P<0.0001).
Upfront therapy was associated with a fracture incidence of 5.7% versus 6.3% in the delayed-therapy group, a nonsignificant difference.
Upfront treatment with zoledronic acid was associated with a 50% reduction in breast cancer recurrence (3.5% versus 6.9%), although the difference was not significant. Calling the findings intriguing, Dr. Brufsky emphasized that the analysis was exploratory.
Neither Dr. Gnant nor Dr. Brufsky disclosed potential conflicts of interest. Z-FAST investigators included employees of Novartis, which funded the study.
Primary source: Breast Cancer Research and TreatmentSource reference:Gnant M, et al "Bone mineral density at 5 years after diagnosis in premenopausal patients with endocrine-responsive breast cancer, after 3 years of adjuvant endocrine treatment with goserelin and tamoxifen or anastrozole or both treatments in combination with zoledronic acid: new results from ABCSG-12" Breast Cancer Res Treat 2007; 106(Supp1 1): S8. Abstract 26. Additional source: Breast Cancer Research and TreatmentSource reference: Brufsky A, et al "The effect of zoledronic acid on aromatase inhibitor-associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole: the Z-FAST study 36-month follow-up" Breast Cancer Res Treat 2007; 106(Suppl 1): S8. Abstract 27.