Most groups of women with early breast cancer who received radiotherapy after mastectomy in clinical trials conducted in the 1960s to 1980s continued to show fewer local recurrences and somewhat reduced breast cancer mortality after 15 years of follow-up, compared with controls who did not receive radiation, according to the latest analysis of the Early Breast Cancer Trialists Collaborative Group (EBCTCG).
PHILADELPHIAMost groups of women with early breast cancer who received radiotherapy after mastectomy in clinical trials conducted in the 1960s to 1980s continued to show fewer local recurrences and somewhat reduced breast cancer mortality after 15 years of follow-up, compared with controls who did not receive radiation, according to the latest analysis of the Early Breast Cancer Trialists Collaborative Group (EBCTCG). The advantages of radiotherapy were evident in women with 1 to 3 positive lymph nodes, a group in which benefits have, until now, been considered uncertain, Paul McGale, PhD, said on behalf of the EBCTCG at the American Society for Therapeutic Radiology and Oncology (ASTRO) 48th Annual Meeting (plenary 4).
The EBCTCG has collected data every 5 years on women with early breast cancer enrolled in clinical trials of various treatments. The new report, which updates the previous analysis (Lancet 366: 2987-2106, 2005), concerns women treated with mastectomy plus axillary dissection and randomly assigned to radiotherapy or a control arm: About 11,000 women participated in 26 trials that started between 1961 and 1984. This database "represents about 97% of the known clinical trials of radiotherapy in this population," said Dr. McGale, of the University of Oxford. [See also page 48.]
Patients in the radiotherapy arms received radiation to the axilla and supraclavicular fossa; most also received chest wall and internal mammary chain radiation. Systemic therapy, usually multiagent chemotherapy and/or tamoxifen, was given in 34% of node-negative and 67% of node-positive patients. Dr. McGale's analysis centered on the nearly 70% of women who had pathologic nodal staging available.
In node-negative women, radiation had little effect on local recurrence by year 5. In women with 1 to 3 positive nodes, radiotherapy was associated with a 15.7% absolute difference in recurrence rate by 5 years. "In other words, for every 100 women treated with radiotherapy, there were 16 fewer local recurrences," he said. In patients with 4 or more positive nodes, the gap in local recurrence rates due to radiotherapy was 22.3%.
Two aspects of these local recurrence curves are worth noting, he said. First, the risk of recurrence in the controls, patients randomized not to receive radiotherapy, is strongly dependent on nodal status. Second, the curves remain relatively flat after year 5, suggesting that "by year 5, most of the local recurrences that are going to happen have happened."
Impact on Mortality
Patterns of breast cancer mortality show the same relationships. In node-negative women, radiation therapy had no significant effect on breast cancer mortality by year 15. In women with 1 to 3 nodes, the difference was significant: 43.3% breast cancer mortality with radiotherapy vs 50.9% without. In women with 4 or more involved nodes, 15-year breast cancer mortality was 69.5% with radiotherapy and 76.4% without.
"One may conclude that if you are successful in substantially reducing the risk of local recurrence, this has an impact on mortality," Dr. McGale said. Specifically, "for every four local recurrences you prevent, about one death from breast cancer is avoided." Radiotherapy was also associated with reduced overall mortality in women with node-positive disease, though the reduction was smaller than the reduction in breast cancer mortality.
These data show that "the greater the risk of local recurrence, the greater the reduction in risk that radiotherapy will give you," he concluded. "If there is little risk of local recurrence, any hazards of radiotherapy play a more significant role." Because more effective systemic therapy is now available, absolute recurrence risks are lower today than when these studies were performed. If so, the absolute gains from radiotherapy may be correspondingly reduced. However, it is also likely that the hazards of radiotherapy are less than they were previously, he said.