RESPONSE: Re: Locoregional Radiation Therapy in Patients With High-Risk Breast Cancer Receiving Adjuvant Chemotherapy: 20-Year Results of the British Columbia Randomized Trial

At 20 years of follow-up, we observed a sustained overall mortality reduction of 27% ( P = .03) in patients receiving locoregional radiotherapy. The tests of interaction performed for all categories of survival showed no difference between subgroups of patients with four or more involved axillary nodes compared with one to three involved axillary nodes ( 1 ) . The relevance of our findings in relation to current treatments has been addressed at length in our Discussion and in the accompanying editorial ( 2 ) . Several points merit emphasis. First, we acknowledge that radiation therapy techniques have changed over time. Improved use of computerized tomography (CT) planning with avoidance of high-dose radiation therapy to the heart may, in fact, yield a greater, rather than smaller, survival benefit from radiation therapy. Second, newer chemotherapy regimens are only marginally more effective than CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) and still require optimal locoregional therapy. Although the use of anthracyclines, taxanes, and transtuzumab may lead to more cardiac events, their consequences may be balanced by improved radiation therapy planning and heart shielding. Furthermore, among patients with one to three involved nodes, it is also possible to identify those with a higher risk as compared with lower risk of recurrence ( 3 , 4 ) with patients at higher risk having a more favorable balance between the benefits and risks of adjuvant radiation therapy ( 3 ) . Some of these selection criteria may have to be applied to current practice, because the mature results of new trials such as the Selective Use of Postoperative Radiotherapy after Mastectomy (SUPREMO) or the Canadian MA-20 will take more than a decade to appear and may still lack the statistical power to address all patient subsets. We agree that further studies of postoperative radiotherapy using current chemotherapy regimens and radiation techniques are warranted. We look forward in due course to reviewing the results of ongoing trials and the refined selection of patients for both adjuvant chemotherapy and radiotherapy. In summary, we believe our findings and those of the Danish Breast Cancer Cooperative Group ( 5 , 6 ) merit discussion with patients who have involved axillary lymph nodes after mastectomy ( 7 ) because appropriate application of these data could prevent thousands of breast cancer deaths annually worldwide.

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