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

Paracelsus Medical University Salzburg, Salzburg, Salzburg, Austria
Journal of Clinical Oncology (Impact Factor: 18.43). 03/2007; 25(7):820-8. DOI: 10.1200/JCO.2005.02.7102
Source: PubMed


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.
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.
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.
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.

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    • "These guidelines and algorithm are dedicated to physicians of all specialties to support clinical relevance of bone loss due to breast cancer treatment and to give guidance on how to reduce the risk of bone fractures. These guidelines were prepared taking into account experience of other countries as well as breast cancer epidemiology and treatment characteristics in Lithuania [1] [2] [3] [4] [5] [6] [7]. Existing Lithuanian guidelines for diagnostics and treatment of osteoporosis and reimbursement conditions by the Lithuanian health insurance fund were also considered [8] [9] [10] "
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    ABSTRACT: The aim of this article is to inform about cancer treatment-induced bone loss, to identify patients at risk and those that can benefit from bone targeted treatment as well as highlight the importance of the multidisciplinary approach in the bone health in cancer care. Patients with breast cancer treated or intended to be treated with aromatase inhibitors belong to a high-risk group because their fracture risk increases up to 30% due to a significant decrease in bone mineral density within 6–12 months after the start of hormonal treatment. To evaluate bone status and predict risk for fractures, lateral thoracic and lumbar spine X-ray imaging, bone mineral density measurement by dual energy X-ray absorptiometry at the lumbar spine L1–L4 vertebrae and/or hip and fracture risk factors assessment are mandatory tests prior to hormonal treatment. Morbidity and mortality associated with bone loss can be prevented with appropriate screening, lifestyle interventions, and therapy. Algorithm for the management of bone health in breast cancer patients was established in Lithuania to screen patients with increased risk for bone loss and to provide adequate specific osteoporosis treatment.
    Full-text · Article · Dec 2014 · Medicina (Kaunas, Lithuania)
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    • "Currently , ZOL , a potent inhibitor of FDPS , is used in the treatment of patients with breast and prostate cancers that have metastasised to the bone , to prevent treatment - associated bone loss in breast cancer , as well as to slow the progression of osteoporosis ( Brufsky et al , 2007 ; Gnant et al , 2007 ) . ZOL has also undergone clinical trials as an adjuvant to standard of care for breast cancer , showing mixed efficacy results ( Brufsky et al , 2007 ; Gnant et al , 2007 ; Coleman et al , 2011 ) . ZOL has been seen to radiosensitise fibrosarcoma ( Koto et al , 2013 ) , osteosar - coma ( Ryu et al , 2010 ) , oesophageal squamous cell carcinoma ( You et al , 2014 ) , and breast cancer cells ( Ural et al , 2006 ) in preclinical studies . "
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    Full-text · Article · Jul 2014 · British Journal of Cancer
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    • "A study [21] suggested that the prevention of continuously decreasing BMD during endocrine treatment with aromatase inhibitors can be increased with the administration of bisphosphonates. Several clinical trials already proved that the combination of AIs with BPs has a potent effect on BMD. "
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