A new meta-analysis by the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) has shown that radiation therapy after surgery for early breast cancer does much more than prevent local recurrence - it significantly improves 15-year survival.

In women with early-stage breast cancer treated with surgery alone, microscopic residual disease may not be eliminated and can eventually cause life-threatening metastatic recurrence. Radiation therapy has been widely recommended for local control after breast-conserving surgery (BCS) and after a complete mastectomy in women at high risk of recurrence. However, even with widespread support for these recommendations within the medical community, they are not always heeded.

Because local recurrence, when detected early, can often be treated with additional surgery alone, some physicians and patients still elect to avoid radiation therapy.

"It was felt, based upon individual trial data, that radiation therapy did not affect overall survival, but just decreased local relapse," says Dr. Jeff Abrams, chief of the Clinical Investigations Branch of NCI's Cancer Therapy Evaluation Program (CTEP).

The EBCTCG meta-analysis strongly suggests that this is not the case. The study, published in the December 17 Lancet, analyzed individual data from 42,000 women, collected during 78 different randomized trials conducted since 1985. The availability of extensive 15-year survival data allowed the investigators to quantify the relationship between successful local control and long-term survivorship.

Radiation therapy after BCS was responsible for a highly significant reduction in local recurrence in all trials. Combined, the data showed a 19 percent absolute reduction of risk of recurrence at 5 years after treatment. None of the trials showed a significant reduction in 15-year mortality when analyzed on their own, but the meta-analysis revealed a highly significant absolute reduction of 5.4 percent.

For women with node-positive (high-risk) tumors who underwent full mastectomy, postoperative radiation therapy provided the same proportional survival benefit as did post-BCS radiation therapy.

The ratio of recurrence reduction to mortality reduction remained the same between subgroups. Subgroups at higher risk of recurrence derived a proportionally larger benefit from radiation therapy. The investigators concluded that "a local treatment difference that reduces the 5-year local recurrence risk by 20 percent would reduce the 15-year breast cancer mortality by 5.2 percent." In other words, says Dr. Abrams, "for every 4 local recurrences that are avoided by the addition of radiation therapy, about 1 breast cancer death could be avoided over the next 15 years."

"This paper really puts it together in a way that no other paper has done before," says Dr. Theodore Lawrence, chairman of Radiation Oncology at the University of Michigan Medical School. "We've known for many years that local control is improved with radiation therapy. We should now feel comfortable that, for high-risk women, radiation therapy improves survival."

The one drawback of radiation therapy noted by the EBCTCG was an increase in the incidence of secondary cancers, and in mortality from heart disease and lung cancer. However, the investigators emphasize that modern radiation therapy technology now minimizes the radiation doses to the heart, lungs, and contralateral breast tissue.

"There should be no increased risk of cardiac death in the modern era," adds Dr. Lawrence. "Women at high risk for recurrence should feel comfortable about getting radiation therapy."

By Sharon Reynolds