1. Goodwin, Peter

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GLASGOW, SCOTLAND-A meta-analysis of long-term historical data has shown that adjuvant radiotherapy brought absolute benefits in terms of progression-free and overall survival to women whose breast cancer involved one, two, or three axillary lymph nodes, just as it did in women whose cancer had spread to four or more nodes, clarifying a long-held uncertainty.

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The findings were reported here at the European Breast Cancer Conference (Abstract 202) by Paul McGale, PhD, a statistician at Oxford University's Clinical Trial Service Unit (CTSU), who said that while there had been a long-time consensus about the lack of benefit from radiotherapy for women without nodal spread of their disease, the jury had been out on whether it could improve outcomes in women with fewer than four positive lymph nodes.


"There simply had not been enough evidence that could enable guidelines to give firm indication of whether or not radiotherapy should be used in women whose cancer has been found in one to three nodes," he explained in an interview after his presentation.


The meta-analysis combined data from randomized clinical trials, comparing similar groups of women with early breast cancer who differed in terms of their allocation to receive or not receive postsurgical radiotherapy. Although this was generally given to the chest wall or the whole breast, in most studies the radiation fields included the axillary and internal mammary lymphatic chains as well.


3,786 Patients

Patient data from 14 individual trials begun before 2000 were analyzed from a total of 3,786 women with or without nodal spread, who were followed for a median of 20.1 years if they had node-negative disease-12.3 years among women with one to three positive nodes and 4.7 years in those with more than four involved nodes.


There was a surprisingly large gain in overall and disease-free survival among women with cancer that had spread to one to three nodes and this was irrespective of whether or not they had also received either chemotherapy or endocrine therapy, McGale said.


"Both categories were very similar: We found that radiotherapy had a very strong effect. Recurrence of any type [distant or regional] was very substantially reduced." Furthermore, there were also corresponding reductions in breast cancer mortality.


In the 1,314 women who had between one and three positive nodes, radiotherapy reduced the recurrence rate by nearly one third (32%) and the breast cancer death rate was down by 20 percent-a rate ratio of 0.80.


McGale said that unsurprisingly the study also confirmed that radiotherapy reduced the recurrence rate (by 21 percent) and the breast cancer death rate (by 13 percent) among 1,772 women who had four or more positive nodes, and that it brought no significant benefit in terms of recurrence or breast cancer mortality to the 700 women who were pathologically node-negative.


When he was asked if such historical data had current clinical relevance, he said he expected that in principle there was a "considerable proportional benefit" to be gained from adjuvant post-surgery radiotherapy and that this would be maintained even in the context of more effective modern chemotherapy and targeted drugs. He acknowledged that modern therapy had changed the absolute risk of recurrence for any particular woman, 'but we would still very much expect a proportional benefit of radiotherapy," he said.


Another coauthor of the meta-analysis, Carolyn Taylor, MD, Consultant Clinical Oncologist from Oxford University Hospitals and a member of the Early Breast Cancer Trialists' Collaborative Group, said she was not surprised by the study findings: "We've never been able to make decisions for women with one to three positive nodes after mastectomy based on large-scale data," she said. But she maintained that the study had now resolved this because the follow-up was long enough to reflect the protracted natural history of breast cancer, which can cause recurrences and deaths many years after diagnosis and treatment.


"One of the benefits of this study is that it followed women for 10 years for recurrences and up to 20 years for breast cancer mortality," Taylor said. "So I think these results will be very useful to guide my treatment of women who have between one and three positive nodes after mastectomy."


The Chair of the sessions on radiotherapy, John Yarnold, MD, Professor of Clinical Oncology at the Institute of Cancer Research, said afterwards that he was impressed by the new data: "It's astonishing, fantastic-the effect of local-regional control is very large. Now it's going to be very difficult not to offer radiotherapy to women with one to three nodes. If you go by evidence-and this is as good as it's going to get-you have to respond to it," he said.


David Cameron, MD, Professor of Oncology at Edinburgh University and Director of Cancer Service at Lothian NHS and one of the organizers of the conference, commented that the data highlight the power of combining information from individual patients recruited into a number of different clinical trials. "The benefit of radiotherapy in women who needed a mastectomy for node positive breast cancer is now becoming clear."