Zoledronic acid protects bone in premenopausal patients with breast ca.(Gynecology)

SAN ANTONIO -- Zoledronic acid prevents the profound loss in bone mineral density that often occurs with combined adjuvant endocrine therapy in premenopausal breast cancer patients, Michael Gnant, M.D., reported at the annual breast cancer symposium sponsored by the Cancer Therapy and Research Center.

Based on new data from the Austrian Breast and Colorectal Cancer Study Group Trial 12 (ABCSG-12), all premenopausal breast cancer patients receiving combination adjuvant therapy with a luteinizing hormone-releasing hormone analog, such as goserelin plus either tamoxifen or an aromatase inhibitor, should undergo annual bone mineral density (BMD) testing. Those showing a treatment-related decline should be considered for intravenous zoledronic acid (Zometa) administered once every 6 months, said Dr. Gnant, professor of surgery at the University of Vienna.

In a separate study presented at the conference, it was reported that zoledronic acid also effectively prevents cancer therapy-induced bone loss in postmenopausal women with early-stage breast cancer on adjuvant aromatase inhibitor therapy.

In clinical practice, the aromatase inhibitors increasingly are replacing tamoxifen, long the standard adjuvant hormonal therapy, because they provide a markedly greater reduction in recurrence along with less risk of endometrial cancer and thromboembolic events.

The price for these advantages has been the greater risk of osteoporosis and fractures associated with aromatase inhibitor therapy. But prophylactic zoledronic acid appears to erase that downside.

While it is widely appreciated that postmenopausal breast cancer patients face increased risk of accelerated bone loss, the osseus impact of cancer therapies in premenopausal breast cancer patients was much less clear before ABCSG-12. The primary end point in the 1,315-patient Phase-III Austrian study will be relapse-free survival, which awaits longer follow-up. In San Antonio, Dr. Gnant reported on a secondary study end point--change in BMD--in a 401-patient subset.

The ABCSG-12 trial is a four-part study that randomized patients to 3 years of adjuvant goserelin plus either tamoxifen or anastrozole, with or without 3 years of zoledronic acid given at 4 mg IV every 6 months. After 3 years of goserelin and tamoxifen without zoledronic acid, BMD at the lumbar spine fell an average of 11.6%, compared with baseline.