PHILADELPHIA — Radiotherapy after mastectomy decreases breast cancer-specific and overall mortality, but only for patients who are at substantial risk of local-regional failure, such as those with node-positive disease, Paul McGale, Ph.D., reported at the annual meeting of the American Society for Therapeutic Radiology and Oncology.
Moreover, if local-regional failure is not a substantial risk, postmastectomy radiotherapy can increase overall mortality, said Dr. McGale, an investigator with the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) and a statistician with the Clinical Trial Service Unit, Oxford, England.
In an EBCTCG meta-analysis of 26 trials with 11,000 women who had undergone axillary clearance, radiotherapy did not reduce 15-year breast cancer-related mortality in women with no nodal involvement (pN0) and overall mortality was poorer with radiotherapy than without it. But on average, 15-year survival was improved for women with pN1–3 or pN4+ disease.
These results provide updated information to guide clinicians in their decisions about which breast cancer patients should receive radiotherapy. The 2000 National Institutes of Health consensus conference recommendations state that women with a high risk of locoregional tumor recurrence after mastectomy (those with pN4+ disease or an advanced primary tumor) would benefit from postoperative radiotherapy (www.consensus.nih.gov/2000/2000AdjuvantTherapyBreastCancer114 html.htm
These recommendations are now supported by the EBCTCG meta-analysis. But at that time, the role of postmastectomy radiotherapy for women with one to three positive lymph nodes was uncertain, and the EBCTCG findings reveal that they too can benefit from radiotherapy.
The EBCTCG was inaugurated in 1984–1985 with the aim of reviewing, every 5 years, the worldwide evidence on the treatment of early breast cancer through direct collaboration among the trialists. According to Dr. McGale, “systematic overviews can help limit selective biases from undue emphasis on particular studies and also help limit random errors in assessing long-term outcome.” Two reports from the fourth 5-year cycle were published last year (Lancet 2005;365:1687–717; Lancet 2005;366:2087–106). The current cycle of data collection involves more than 150 trial centers with more than 300,000 women with breast cancer randomized to approximately 400 trials over the past few decades.
During the first 9 years of the meta-analysis, 5,000 women died, and from year 10 onward, 2,000 women died, Dr. McGale said. In all trials, radiotherapy was directed at the axilla or supraclavicular fossa, and in most trials, it involved the chest wall and internal mammary chain. A total of 34% of 1,847 node-negative patients and 67% of 9,106 node-positive patients received systemic therapy.
The meta-analysis showed that at 15 years, radiotherapy had no significant effect on breast cancer mortality in women with pN0 disease; however, women with pN1–3 or pN4+ disease who received radiotherapy had lower mortality rates than those who did not. With regard to all-cause mortality, radiotherapy had a clear detrimental effect on patients with pN0 disease but significantly benefited patients with nodal involvement. (See box.)
Dr. McGale noted that overall mortality after radiotherapy is a balance of benefits and hazards. “With better radiotherapy regimens, reductions in breast cancer mortality may be more, and hazards of radiotherapy may be less. If absolute recurrence risks are lower nowadays, absolute gains from radiotherapy may be correspondingly lower,” he said.
In a discussion, Dr. Abram Recht of the department of radiation oncology at Harvard Medical School, Boston, noted that although the EBCTCG meta-analysis has the typical advantages of meta-analyses (large patient numbers, reduction of publication bias), it has limited or no data on important prognostic factors, such as histopathology and hormone receptor status. Also, the efficacy and toxicity of treatments used in different trials may vary markedly, but these factors tend to be overlooked. And finally, the results do not give information about the long-term toxicity of more modern postmastectomy radiotherapy regimens, especially in combination with cardiotoxic systemic therapy, he said.
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