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.
“The big thing about radiotherapy is it 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 techniques achieve it with much less cardiotoxicity than the radiotherapy of the 1980s, then physicians can expect to see a continued further decline in overall mortality in breast cancer patients in the decade beginning in 2010, he said.
“Local recurrence is not a cosmetic problem, it's a life-or-death problem,” 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. The question is not 5-year survival, 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.
“With a quarter of a million woman-years of observation after year 5, we've got really clear results,” he noted.
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, compared with 48% in controls. “It's a small but real benefit,” Dr. Peto said.
Through stratification of trials based upon 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, compared with 29% in controls. Ten-year breast cancer mortality was 17% in radiotherapy-treated women and 20% in controls.
The EBCTCG data show that in addition to the marked increase in late cardiovascular deaths associated with radiation therapy as practiced in the 1980s, treated women also face smaller but nonetheless 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 in recent decades even comes close—and that's not due to screening and treatment advances, but, rather, to smoking cessation efforts.