1. Home>
2. Specialties>
3. Women's Health>
4. Summary and Comment

Adding Zoledronic Acid to Endocrine Therapy for Premenopausal Breast Cancer

European trial results suggest that adding IV bisphosphonate therapy improves outcomes.

Results of a 2008 industry-funded Austrian trial showed that intravenous administration of the bisphosphonate, zoledronic acid (ZA; Reclast), prevented bone-density loss in premenopausal women with receptor-positive breast cancer who received ovarian-suppression therapy (JW Womens Health Sep 25 2008). In a substudy, investigators have assessed ZA’s effect on cancer-related outcomes. Eligible participants were premenopausal; had undergone primary surgery for stage I or II breast cancer that was estrogen-receptor positive, progesterone-receptor positive, or both; and were scheduled to initiate ovarian-suppression therapy with the gonadotropin-releasing hormone agonist goserelin (Zoladex). Women received postoperative radiation therapy but not adjuvant chemotherapy and were randomized to receive goserelin plus either tamoxifen or the aromatase inhibitor anastrozole (Arimidex) for 3 years. In each treatment arm, participants were allocated to receive ZA (4 mg IV every 6 months) or no ZA.

Median follow-up was 48 months for the 1803 participants (median age at study entry, 45). Rates of disease-free survival were higher among women who received ZA than among those who did not (94.0% vs. 90.8%; P=0.01), resulting in a 36% lower risk for disease progression with endocrine treatment plus ZA versus endocrine treatment alone. Randomization to ZA was associated with fewer events related to breast cancer (e.g., locoregional and distant recurrence, bone metastases, contralateral breast disease). Women who received ZA were more likely to report bone pain (35% vs. 25%), arthralgias (24% vs. 18%), and fever (9% vs. 2%) than those who did not receive ZA. No documented cases of osteonecrosis of the jaw were observed.

Comment: Use of ovarian-suppression therapy rather than cytotoxic chemotherapy deserves comment. In the U.S., chemotherapy conventionally is offered to premenopausal women after initial surgery or radiation therapy for low- or intermediate-risk receptor-positive breast cancer; however, in other countries, ovarian-suppression therapy is often employed in this setting. These findings suggest that good outcomes can be achieved with ovarian-suppression therapy and that addition of ZA further improves outcomes. Antitumor effects exerted by ZA seem to promote beneficial results, both within the skeleton and at nonskeletal sites in premenopausal breast cancer patients who receive ovarian-suppression therapy.

— Andrew M. Kaunitz, MD

Published in Journal Watch Women's Health February 11, 2009

Citation(s):

Gnant M et al. Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med 2009 Feb 12; 360:679.

• Original article (Subscription may be required)
• Medline abstract (Free)