Breast Cancer: New Radiation Treatment Options

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Six published randomized trials[ 1-6] and one meta-analysis[ 7] of published and unpublished trials have demonstrated that breast-conserving therapy (breast-conserving surgery plus breast irradiation) is equivalent to mastectomy in terms of survival.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.


The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.


1. Arriagada R, Le MG, Rochard F, et al: Conservative treatment versus mastectomy in early breast cancer: Patterns of failure with 15 years of follow-up data. Institut Gustave- Roussy Breast Cancer Group. J Clin Oncol 14:1458-1464, 1996.
2. Blichert-Toft M, Rose C, Andersen JA, et al: Danish randomized trial comparing breast conservation therapy with mastectomy: Six years of life-table analysis. Danish Breast Cancer Cooperative Group. J Natl Cancer Inst Monogr 11:19-25, 1992.
3. Fisher B, Redmond C, Poisson R, et al: Eight-year results of a randomized clinical trial comparing total mastectomy and lumpectomy with or without irradiaton in the treatment of breast cancer. N Engl J Med 320:822-828, 1989.
4. Van Dongen JA, Voogd AC, Fentiman IS, et al: Long-term results of a randomized trial comparing breast-conserving therapy with mastectomy: European Organization for Research and Treatment of Cancer 10801 trial. J Natl Cancer Inst 92:1143-1150, 2000.
5. Veronesi U, Banfi A, Salvadori B, et al: Breast conservation is the treatment of choice in small breast cancer: Long-term results of a randomized trial. Eur J Cancer 26:668-670, 1990
6. Jacobson JA, Danforth DN, Cowan KH, et al: Ten-year results of a comparison of conservation with mastectomy in the treatment off stage I and II breast cancer. N Engl J Med 332:907-911, 1995.
7. Early Breast Cancer Trialists’ Collaborative Group: Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomized trials. Lancet 355:1757-1769, 2000.
8. Whelan T, Levine M, Willan A, et al: Effect of a decision aid on knowledge and treatment decision making for breast cancer surgery: A Randomized Trial. JAMA 292:435-441, 2004.
9. Fisher B, Anderson S, Bryant J, et al: Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 347:1233-1241, 2002.
10. Liljegren G, Holmberg L, Bergh J, et al: 10-year results after sector resection with or without postoperative radiotherapy for stage 1 breast cancer: a randomized trial. J Clin Oncol 17:2326-2333, 1999.
11. Clark RM, Whelan T, Levine M, et al: Randomized clinical trial of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer: An update. J Natl Cancer Inst 88:1659-1664, 1996.
12. Veronesi U, Luini A, Del Vecchio M, et al: Radiotherapy after breast-preserving surgery in women with localized cancer of the breast. N Engl J Med 328:1587-1591, 1993.
13. Forrest AP, Stewart HJ, Everington D, et al: Randomised controlled trial of conservation therapy for breast cancer: 6-year analysis of the Scottish trial. Lancet 348:708-713, 1996.
14. Holli K, Saaristo R, Isola J, et al: Lumpectomy with or without postoperative radiotherapy for breast cancer with favourable prognostic features: Results of a randomized study. Br J Cancer 84:164-691, 2001.
15. Malström P, Holmberg L, Anderson H, et al, for the Swedish Breast Cancer Group: Breast conservation surgery, with and without radiotherapy, in women with lymph node-negative breast cancer: A randomized clinical trial in a population with access to public mammography screening. Eur J Cancer 39:1690-1697, 2003.
16. Vinh-Hung V, Verschraegen C: Breast conserving surgery with or without radiotherapy: Pooled-analysis for risks of ipsilateral breast tumor recurrence and mortality. J Natl Cancer Inst 96:115-121, 2004.
17. Nattinger AB, Hoffmann RG, Kneusel RT, et al: Relation between appropriateness of primary therapy for early-stage breast carcinoma and increased use of breast-conserving surgery. Lancet 30:356: 1148-1153, 2000.
18. Morrow M, White J, Moughan J, et al: Factors predicting the use of breast-conserving therapy in stage I and II breast carcinoma. J Clin Oncol 19:2254-2262, 2001.
19. McGinnis LS, Menck HR, Eyre HJ, et al: National Cancer Data Base Survey of breast cancer management for patients from low income zip codes. Cancer 88:933-945, 2000.
20. Atas WF, Adams-Cameron M, Hunt WC, et al: Travel distance to radiation therapy and receipt of radiotherapy following breast-conserving surgery. J Natl Cancer Inst 92:269-271, 2000.
21. Whelan TJ, Levine M, Julian J, et al: The effects of radiation therapy on quality of life of women with breast carcinoma: Results of a randomised trial. Ontario Clinical Oncology Group. Cancer 88:2260-2266, 2000.
22. Whelan T, Mackenzie R, Julian J, et al: Randomized trial of breast irradiation schedules after lumpectomy with lymph node-negative breast cancer. J Natl Cancer Inst 94:1143- 1150, 2002.
23. Yarnold J, Owen R, Ashton A, et al: Fractionation sensitivity of change in breast appearance after radiotherapy for early breast cancer: Results of a phase III randomized trial (abstract 154). Breast Cancer Res Treat 69:230, 2001.
24. Lymon JT: Compication probability as assessed from dose-volume histograms. Radiat Res Suppl 8(suppl 1):3-9, 1985.
25. Veronesi U, Cascinelli N, Mariani L, et al: Twenty-year follow-up of a randomized study comparing breast conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 347:1227-1232, 2002.
26. Ribeiro GG, Magee B, Swindell R, et al: The Christie Hospital Breast Conservation Trial: An update at 8 years form inception. Clin Oncology 5:278-283, 1993.
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