Breast Cancer: New Radiation Treatment Options

Six published randomized trials[ 1-6] and one meta-analysis[ 7] of published and unpublished trials have demonstrated that breast-conserving therapy (breast-conserving surgery plus breast irradiation) is equivalent to mastectomy in terms of survival. As a result, breastconserving therapy is the option preferred by many women for the treatment of early-stage breast cancer.[ 8] Breast irradiation following breast-conserving surgery is an integral part of breast-conserving therapy. There are seven other published randomized trials demonstrating that breast irradiation substantially reduces the rate of local recurrence and prevents the need for subsequent mastectomy.[ 9-15] A recent meta-analysis also supports the conclusion that breast cancer patients who receive breast irradiation have improved survival.[16] Despite this demonstrated effectiveness, up to 30% of patients treated with breast-conserving surgery may not receive radiation therapy.[17,18] The reasons for this are multifactorial, but they are primarily related to the inconvenience, side effects, and cost of treatment.[19,20] While breast irradiation is generally well tolerated, it is an inconvenient treatment that requires daily visits for up to 6 or 7 weeks. Common early toxicities include fatigue, breast pain, edema, skin erythema, and irritation, all of which can have a significant impact on quality of life.[21] The difficulties encountered in delivering and receiving radiation treatment are believed to account for the poor utilization of breastconserving therapy in some regions of North America. Modified Radiation Strategies
In an effort to improve convenience and quality of life for patients who receive breast irradiation, investigators have evaluated shorter or accelerated radiation therapy schedules. A Canadian trial compared accelerated whole-breast irradiation given in 3 weeks to a more conventional course of whole-breast irradiation given in 5 weeks.[22] With a median followup of approximately 6 years, the rates of local recurrence and adverse cosmetic outcome as a measure of late morbidity were equivalent between the two approaches. A similar randomized trial in the United Kingdom evaluating less frequent radiation treatments demonstrated similar findings.[23] As a result, accelerated wholebreast irradiation is now an option for women, to improve convenience and decrease costs associated with breast irradiation following breast-conserving surgery. While there remains some concern about potentially increased long-term morbidity associated with accelerated therapy, the results obtained so far suggest that this outcome is unlikely to be substantially worse than that seen with conventional treatment. Accelerated wholebreast irradiation is now widely used in Canada and the United Kingdom. The article by Arthur et al in this journal provides a thorough summary of the next generation of accelerated radiation therapy approaches following breast-conserving surgery. Radiation morbidity is directly related to the volume of tissue irradiated.[24] By delivering only partial-breast irradiation, larger doses of radiation can be delivered in an even shorter period of time (1 to 5 days) with the expectation that there will be limited morbidity. A number of approaches have been developed, including interstitial brachytherapy, the MammoSite device, three-dimensional conformal therapy, and intraoperative treatment. Some of these approaches, especially interstitial brachytherapy, have undergone extensive phase II testing and are now being evaluated in phase III randomized trials. Importance of Clinical Trials
As indicated by the authors, it is likely that with careful selection of patients and the use of appropriate quality assurance measures, a number of these approaches may prove to be equally effective to current wholebreast irradiation. However, it is important that these approaches be carefully evaluated. Previous advances in breast-conserving treatment have been based on carefully performed phase II and extensive phase III testing. As a result, our current approach to breast-conserving therapy as compared to more radical surgery, has been shown to result in equivalent outcomes for women for up to 20 years following treatment.[9,25] It is of some interest that the only randomized trial of partial-breast irradiation performed more than 10 years ago demonstrated decreased local control and worse cosmetic outcome as compared to whole-breast irradiation.[26] This has been attributed to suboptimal selection of patients and inadequate techniques for tumor localization. In the next decade, it will be important to build on our previous successes through carefully performed research studies. Advances in Technology
Other recent advances in radiation therapy for breast cancer have been the application of technology to adequately localize the tumor cavity, identify critical structures, and provide a more homogeneous dose. These advances have included the use of computed tomography (CT) planning and intensity-modulated radiation therapy (IMRT). IMRT utilizes modern technology to deliver a number of radiation fields and to vary the intensity of these fields. As Arthur and colleagues point out in their review, numerous studies have now demonstrated that IMRT results in improved homogeneity of the dose to the breast and decreased exposure to the heart and lungs. This application may be of particular relevance for locoregional radiation where the target extends beyond the breast and chest wall to include the regional nodes at risk, which would normally increase the risk of additional radiation to the lungs and heart. IMRT compared to conventional techniques may be associated with increased low-dose radiation exposure to tissues beyond the breast-eg, thyroid and contralateral breast-so, again, it is imperative that such approaches be formally evaluated in prospective phase III trials. Conclusions
The newer approaches to radiation therapy for breast cancer are exciting and hold much promise. As we move forward, we must not forget that advances in the local treatment of breast cancer have come through rigorous evaluation resulting in high levels of local control that can be consistently achieved in many different institutions. New treatment approaches are attractive from the perspectives of applied technology, reduction in morbidity, improvement in patient convenience, and decreased costs. However, these approaches need to meet the high standards of established radiation therapy techniques through equally rigorous evaluation, to ensure that these potential advantages do not come at the expense of local control or unacceptable side effects.