letters to the editor |
Reply to Letter to the editor, by E. Yaman et al. (Ann Oncol)
Yaman et al. [1] comment on the patient population included in our study demonstrating the noninferiority of oral ibandronate to intravenous zoledronic acid for reducing markers of bone turnover in women with metastatic bone disease from breast cancer [2]. They express concerns about the balance between the two treatment groups for the proportion of patients receiving hormonal therapy. While tamoxifen can indeed reduce bone loss through inhibition of osteoclasts, it is well documented that aromatase inhibitors accelerate bone turnover and increase the subsequent risk of osteopenia or osteoporosis in postmenopausal women with breast cancer [3–5]. Similarly, adjuvant chemotherapy for premenopausal patients can cause ovarian suppression and impaired oestrogen/progesterone cycling, leading to a greater likelihood of bone loss and fracture [6].
While it may be difficult to separate out the different possible effects on bone turnover of individual concomitant cancer treatments in clinical trials of bisphosphonates, we believe that a sub-analysis of our study population based on baseline cancer therapy is unnecessary. As stated in our original article, the oral ibandronate and zoledronic acid groups were well balanced in terms of the number and types of concomitant tumor treatments received (
94% of patients in each group) [2]. Although the percentage of patients receiving tamoxifen was slightly higher in the oral ibandronate group compared with the zoledronic acid group (32.1% versus 24.1%), this was also the case for the aromatase inhibitors anastrazole (16.8% versus 14.6%) and letrozole (14.6% versus 13.9%), and the chemotherapeutic agents doxorubicin (11.0% versus 10.2%) and cyclophosphamide (11.7% versus 8.8%), all of which would be expected to increase bone loss, rather than to preserve it. The percentage of patients receiving trastuzumab was very low and similar between groups [ibandronate 1.5% (n = 2) versus zoledronic acid 2.2% (n = 3)], so this is unlikely to have any measurable impact on the bone marker results from the trial.
Perhaps most importantly, the baseline levels of all bone resorption and formation markers evaluated [serum and urinary cross-linked C-terminal telopeptide of type I collagen (CTX), bone-specific alkaline phosphatase, amino-terminal procollagen propeptide of type I collagen and osteocalcin] were similar between the two treatment groups at baseline (as was shown in Figures 2 and 3) [2]. If the percentage of patients receiving tamoxifen in the oral ibandronate group conferred any unfair advantage for greater preservation of skeletal integrity, surely this would have been evident by lower CTX levels in this group before starting the bisphosphonate treatment period. This was clearly not the case.
Institut Jules Bordet, Université Libre de Bruxelles, 1 Rue Héger-Bordet, 1000 Brussels, Belgium
(E-mail: jj.body{at}bordet.be)
References
1. Yaman E, Benekli M, Ugur C, et al. Letter to editor. Re: oral ibandronate is as active as intravenous zoledronic acid for reducing bone turnover markers in women with breast cancer and bone metastases. Ann Oncol (2007) DOI:10.1093/annonc/mdm577.
2. Body JJ, Lichinitser M, Tjulandin S, et al. Oral ibandronate is as active as intravenous zoledronic acid for reducing bone turnover markers in women with breast cancer and bone metastases. Ann Oncol (2007) 18(7):1165–1171.
3. Body JJ, Bergmann P, Boonen S, et al. Management of cancer treatment-induced bone loss in early breast and prostate cancer—a consensus paper of the Belgian Bone Club. Osteoporos Int (2007) 18(11):1439–1450.[CrossRef][Web of Science][Medline]
4. Confavreux CB, Fontana A, Guastalla JP, et al. Estrogen-dependent increase in bone turnover and bone loss in postmenopausal women with breast cancer treated with anastrozole. Prevention with bisphosphonates. Bone (2007) 41(3):346–352.[Medline]
5. Rugo HS. Strategies for the prevention of treatment-related bone loss in women receiving adjuvant hormonal therapy. Clin Breast Cancer (2007) 7(Suppl 1):S21–S28.[Web of Science][Medline]
6. Pfeilschifter J, Diel IJ. Osteoporosis due to cancer treatment: pathogenesis and management. J Clin Oncol (2000) 18(7):1570–1593.
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