Originally published as JCO Early Release 10.1200/JCO.2005.02.7102 on December 11 2006

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Zoledronic Acid Prevents Cancer Treatment–Induced Bone Loss in Premenopausal Women Receiving Adjuvant Endocrine Therapy for Hormone-Responsive Breast Cancer: A Report From the Austrian Breast and Colorectal Cancer Study Group

Michael F.X. Gnant, Brigitte Mlineritsch, Gero Luschin-Ebengreuth, Stephan Grampp, Helmut Kaessmann, Marianne Schmid, Christian Menzel, Jutta Claudia Piswanger-Soelkner, Arik Galid, Martina Mittlboeck, Hubert Hausmaninger, Raimund Jakesz

From the Departments of Surgery, Radiology, and Osteology; Core Unit for Medical Statistics and Informatics; and Division of Special Gynecology, General Hospital, Medical University of Vienna, Vienna; Departments of Internal Medicine III, and Nuclear Medicine and Endocrinology, Breast Center Salzburg, Paracelsus Private Medical University Salzburg, Salzburg; Department of Gynecology and Obstetrics; Department of Internal Medicine, Division of Oncology; and Department of Internal Medicine, Division of Endocrinology and Nuclear Medicine, Medical University Graz, Graz, Austria

Address reprint requests to Michael Gnant, MD, Medical University of Vienna, Department of Surgery, Währinger GürA-1090, Vienna, Austria; e-mail: michael.gnant{at}meduniwien.ac.at

Purpose Adjuvant therapy for breast cancer can be associated with decreased bone mineral density (BMD) that may lead to skeletal morbidity. This study examined whether zoledronic acid can prevent bone loss associated with adjuvant endocrine therapy in premenopausal patients.

Patients and Methods This study is a randomized, open-label, phase III, four-arm trial comparing tamoxifen (20 mg/d orally) and goserelin (3.6 mg every 28 days subcutaneously) ± zoledronic acid (4 mg intravenously every 6 months) versus anastrozole (1 mg/d orally) and goserelin ± zoledronic acid for 3 years in premenopausal women with hormone-responsive breast cancer. In a BMD subprotocol at three trial centers, patients underwent serial BMD measurements at 0, 6, 12, 24, and 36 months.

Results Four hundred one patients were included in the BMD subprotocol. Endocrine treatment without zoledronic acid led to significant (P < .001) overall bone loss after 3 years of treatment (BMD, –14.4% after 36 months; mean T score reduction, –1.4). Overall bone loss was significantly more severe in patients receiving anastrozole/goserelin (BMD, –17.3%; mean T score reduction, –2.6) compared with patients receiving tamoxifen/goserelin (BMD, –11.6%; mean T score reduction, –1.1). In contrast, BMD remained stable in zoledronic acid–treated patients (P < .0001 compared with endocrine therapy alone). No interactions with age or other risk factors were noted.

Conclusion Endocrine therapy caused significant bone loss that increased with treatment duration in premenopausal women with breast cancer. Zoledronic acid 4 mg every 6 months effectively inhibited bone loss. Regular BMD measurements and initiation of concomitant bisphosphonate therapy on evidence of bone loss should be considered for patients undergoing endocrine therapy.

published online ahead of print at www.jco.org on December 11, 2006.

Supported in part by AstraZeneca and Novartis Pharmaceuticals.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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