We read the interesting article by Jagsi et al on the increased rates of coronary artery disease in patients treated with radiation therapy for early-stage breast cancer.1 In their study, those authors concluded that the findings support further assessment of clinical outcomes when newer techniques of chemotherapy planning are employed as well as investigation of the potential role of innovative techniques. However, there was no mention of the novel radiosensitizing and chemosensitizing effects of bisphosphonates (BPs), which inhibit tumor cell adhesion to bone, and tumor growth in breast cancer.

We recently demonstrated that zoledronic acid (ZOL), the third-generation of BPs, increased disease-free survival in pristine-induced plasmacytoma in BALB/c mice.2 In another study, we demonstrated that using the combination of ZOL and radiation always synergistically enhanced growth inhibition of breast cancer cells compared with either agent alone.3 The results from the combination of ZOL and radiation are novel and intriguing, because they immediately suggest the clinical utility of using ZOL combined with radiation to avoid serious side effects of radiotherapy, especially in patients with breast cancer.

All of these results raise the possibility that nitrogen-containing BP, ZOL, with its direct antitumor effect and as a radiosensitizing and chemosensitizing agent, may be a valuable adjunct to the treatment of patients with breast cancer. Combining BP treatment with radiation or chemotherapy produces the same effect with a lower radiation dose or lower fraction numbers, thus avoiding serious cardiac side effects of radiotherapy.


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Ali U. Ural MD* †, Ferit Avcu MD* †, Yusuf Baran MD‡, * Department of Hematology Gulhane Military Medical Academy Ankara, Turkey, † Department of Medical and Cancer Research Center Gulhane Military Medical Academy Ankara, Turkey, ‡ Department of Biology Izmir Institute of Technology Izmir, Turkey.