SAN ANTONIO — The improved local control of breast cancer achieved via radiotherapy translates into a significant reduction in mortality due to the malignancy that becomes apparent only late, at 10 and 15 years' follow-up, Sir Richard Peto, Ph.D., reported at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.
That's the good news regarding radiotherapy from a new metaanalysis of the world's total randomized clinical trial experience in early breast cancer. The bad news: This reduction in breast cancer mortality is essentially canceled out—and in some subgroups outweighed—by a radiotherapy-induced excess in late deaths due to cardiovascular disease.
Radiotherapy “causes deaths from heart disease not in the first decade after treatment but in the second,” said Dr. Peto, professor of medical statistics and epidemiology at the University of Oxford (England).
Still, the central point remains: Local control of breast cancer matters. And if preliminary evidence turns out to be correct in suggesting modern radiotherapy achieves it with less cardiotoxicity than the radiotherapy of the 1980s, then physicians can expect to see a further decline in overall breast cancer mortality in the decade beginning in 2010, he said.
“Breast cancer is a disease where you've really got to think of what you're achieving on a time scale of decades, not years,” he said. “The question for a middle-aged woman is what is the 20-year survival?”
Dr. Peto presented a metaanalysis of data from the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) involving 24,000 women randomized to radiotherapy or no radiotherapy in 46 clinical trials that enrolled patients in the mid-1980s.
The 15-year rate of isolated local recurrence was 10% in women who received radiotherapy and 31% in those who did not. And 15-year mortality due to breast cancer was 44% in radiotherapy recipients and 48% in controls.
With trials stratified based on the magnitude of difference in local control, it became apparent that the greater the difference in local control in a given study, the bigger the long-term difference in breast cancer mortality, he said.
Looking more narrowly at the impact of radiotherapy after breast-conserving therapy in a series of randomized trials involving 6,097 women with node-negative disease, he found that the 10-year rate of isolated local recurrence was 10% in those who got radiotherapy and 29% in controls. Ten-year breast cancer mortality was 17% in radiotherapy-treated women and 20% in controls.
The EBCTCG data show that besides the increase in late cardiovascular deaths associated with radiation therapy as practiced in the 1980s, treated women face smaller but significant increases in risk of death due to lung, esophageal, and contralateral breast cancer.
Nevertheless, he characterized the overall improvement in breast cancer outcomes since the 1980s as “a brilliant success.” It's estimated that in 2010, mortality in middle age due to breast cancer in the United Kingdom will be just half of what it was in 1980, and a similar trend applies in the United States.
That's a success story unrivaled in oncology. Only the reduction in lung cancer deaths even comes close—and that's not due to medical advances but to smoking cessation efforts.
“The changes in breast cancer treatment during the 1980s produced changes in mortality in the 1990s. The improvements in treatment and in screening in the 1990s are going to produce continuing reductions in mortality in this decade. And the improvements coming now in treatment are going to keep those reductions in mortality going in the 2010s,” Dr. Peto predicted.