Researchers from Austria and Germany found that adding the bone drug zoledronic acid to endocrine therapy improved disease-free survival in
premenopausal women with early stage breast cancer of the estrogen-responsive type.
The research was the work of lead author Dr Michael Gnant of the Medical University of Vienna in Austria and colleagues from other research centres in Austria and Germany and is published online in the 12 February issue of the New England Journal of Medicine.
Zoledronic acid is normally used to prevent bone fractures in patients with cancer and to treat bone diseases such as postmenopausal osteoporosis; it is is marketed by Novartis as Zometa, Zomera, Aclasta and Reclast.
Some pre-clinical studies have suggested that zoledronic acid has antitumor properties, so the researchers decided to investigate the effect of adding it to the standard treatment for premenopausal women with endocrine-receptive early breast cancer.
For the study, the researchers recruited 1,803 premenopausal women with early stage endocrine-responsive breast cancer and randomly assigned them to receive goserelin (stops the production of estrogen) and tamoxifen, or anastrozole (an aromatase inhibitor normally used to treat postmenopausal women with breast cancer) with or without zoledronic acid. The women underwent the therapy for three years.
The primary outcomes that the researchers looked for were disease-free survival and recurrence-free survival, with overall survival as a secondary measure.
After a median follow up of 47.8 months, 137 events had occurred, with the following results:
- The disease-free survival in the tamoxifen group was 92.8 per cent.
- In the anastrozole group it was 92.0 per cent, with 90.8 in the endocrine therapy only subgroup and 94.0 per cent in the subgroup that also received zoledronic acid.
- There was no significant difference in disease-free survival between the tamoxifen and anastrozole groups.
- Compared to endocrine therapy alone, adding zoledronic acid resulted in an absolute reduction of 3.2 per cent and a relative reduction of 36 per cent in the risk of disease progression.
- Adding zoledronic acid did not significantly reduce the risk of death.
- There were no unexpected adverse events, these were within known safety profiles for the drugs concerned.
- Women who received zoledronic acid were more likely to report bone pain (35 vs 25 per cent), arthralgias (24 vs 18 per cent), and fever (9 vs 2 per cent) than those who did not.
- No documented cases of osteonecrosis of the jaw were observed.
"The addition of zoledronic acid to adjuvant endocrine therapy improves disease-free survival in premenopausal patients with estrogen-responsive early breast cancer."
Writing in NEJM's Journal Watch, Women's Health, Deputy Editor Dr Andrew Kaunitz, who is Professor and Associate Chair of the Department of Obstetrics and Gynecology at the University of Florida College of Medicine, drew attention to the differences between US practice and the methods used in other countries such as reflected in this Austro-German study:
"Use of ovarian-suppression therapy rather than cytotoxic chemotherapy deserves comment. In the US, 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."
Commenting on the findings, Kaunitz wrote they:
"Suggest that good outcomes can be achieved with ovarian-suppression therapy and that addition of ZA [zoledronic acid] 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," added Kaunitz.
"Endocrine Therapy plus Zoledronic Acid in Premenopausal Breast Cancer."
Gnant, Michael, Mlineritsch, Brigitte, Schippinger, Walter, Luschin-Ebengreuth, Gero, Postlberger, Sabine, Menzel, Christian, Jakesz, Raimund, Seifert, Michael, Hubalek, Michael, Bjelic-Radisic, Vesna, Samonigg, Hellmut, Tausch, Christoph, Eidtmann, Holger, Steger, Gunther, Kwasny, Werner, Dubsky, Peter, Fridrik, Michael, Fitzal, Florian, Stierer, Michael, Rucklinger, Ernst, Greil, Richard, the ABCSG-12 Trial Investigators.
N Engl J Med Volume 360, Number 72, pp 679-691, published online February 12, 2009
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Written by: Catharine Paddock, PhD