We appreciate Ural and colleagues' comments in response to our article.1 Our findings support the investigation of novel approaches to minimize cardiac toxicity from the treatment of breast cancer. Novel methods of radiation therapy administration seem to be the most appropriate targets for investigation, because more conformal techniques may permit a lower dose to cardiac structures while maintaining an adequate tumoricidal dose to targeted structures. However, we agree with Ural and colleagues that other innovative approaches also may prove useful to this end, including the possibility of combining radiation therapy with other agents. Nevertheless, it is important to note that such combination therapy must be proven to provide an enhanced therapeutic ratio compared with standard treatment with radiation alone. We believe that it is extremely premature to speculate that “combining bisphosphonate therapy with radiation…produces the same effect with lower radiation dose…avoiding serious cardiac side effects of radiotherapy.” Like with any new approach, the use of bisphosphonates, if supported by preclinical data, must be explored carefully in the clinical setting with Phase I, II, and III studies to determine whether it actually is safe and efficacious to administer these agents in combination with radiation therapy in the setting of adjuvant treatment of breast cancer. Only after long-term follow-up from clinical studies may we determine whether this proposed approach may have any impact in reducing the potential for radiation-related cardiac toxicity while maintaining adequate tumor control.