Zoledronic Acid Significantly Reduced Relapse in Early Breast Cancer

A recent Austrian trial presented at the American Society of Clinical Oncology meeting in May 2008 showed that 4mg of Zoledronic Acid given twice a year significantly reduced relapse in early breast cancer.

Zoledronic acid is already marketed in Australia as Zometa by Novartis for use in the treatment of bone metastases.

Following surgery, women who had not reached the menopause were treated with the lutenizing hormone-releasing hormone (LHRH) agonist goserelin for ovarian suppression, combined with either the antiestrogen drug tamoxifen or the aromatase inhibitor anastrozole (Arimidex, AstraZeneca).

In addition, 1 group of women also received zoledronic acid (4 mg intravenously every 6 months). Treatment was continued for 3 years.

After a median follow-up of 5 years, there were 54 events in the zoledronic acid group and 83 events in the 2 goserelin groups (hazard ratio, 0.64; P = .015). This translates into a 36% reduction in the risk for disease progression, Dr. Gnant added. There was a significant reduction in locoregional disease progression (10 events in the zoledronic acid group vs 20 events in the 2 goserelin groups) and distant metastases, both bone and nonbone (29 events in the zoledronic acid group vs 41 events in the 2 goserelin groups).

None of the 1800 women in this study received adjuvant chemotherapy after their surgery and only 5% received it before their surgery. They all had hormone therapy.

At five years, 137 women (7.6%) had had a recurrence, while 42 (2.3%) deaths occurred. This means this study found a 98% chance of survival in young women who are given ovarian suppression and hormone therapy drugs but do receive any chemotherapy.

This is an importnat aspect of the study and certainly supports the view that many young women with small ER-positive may be being overtreated with chemotherapy.

Also, the study found that there was no difference between in recurrence risk in the women who took tamoxifen and those who took an aromatase inhibitor. This again is critically important as in my view, Tamoxifen is better tolerated in this age group with less sexual side-effects.


In the group that received Zometa, 39 had a recurrence and six developed contralateral breast cancer. In the group that did not received Zometa, 61 had a recurrence and 10 developed contralateral breast cancer. This was a statistically significant, 36% reduction in recurrence.

However, with zoledronic acid the most serious side effect is an increased risk of developing osteonecrosis of the jaw. The researchers monitored the women closely and no cases were seen as yet.

It's very important to note that this study was done in premenopausal women who were on hormone therapy to suppress ovarian function. The findings may not hold true for women who have had cehemotherapy or perhaps for women with hormone receptor negative cancers. We also don't know if the findings will be true for postmenopausal women.

For the moment we should keep an eye on this and other studies before we recommend it in routine practice but this is a good study worthy of a change in practice for selected patients.

The NCI in the US summarised this study

NCI report of Zoledronic acid study