MILAN—The benefit of adding whole breast irradiation (WBI) to breast-conserving therapy in the treatment package for patients with low-risk hormone receptor-positive early breast cancer was confirmed after 10 years of follow-up by data from the Austrian Breast & Colorectal Cancer Study Group A8 trial reported at the European Society for Radiotherapy and Oncology (ESTRO) (Abstract OC-0270).
Five-year follow-up of the same study had previously demonstrated the clear superiority of adding radiotherapy to standard anti-hormone therapy with tamoxifen and anastrozole.
“Patients irradiated had significantly lower recurrence rates than patients treated with anti-hormones alone,” said Gerd Fastner, MD, radiation oncologist and Associate Professor at the Paracelsus Medical University of Salzburg, Austria. “Now at 10 years we've confirmed the data. There was also a significant impact on disease-free survival.”
The A8 study looked at the cumulative incidences of local recurrences in the breast and the chest wall. Clinical endpoints included overall survival, disease-free survival, and local regional survival. “We found a significant benefit in local control and in disease-free survival for patients who were treated with radiation therapy,” Fastner noted.
No significant benefit from adjuvant radiotherapy had been detected after 10-years follow-up in overall survival, regional relapse-free survival, or metastasis-free survival.
Altogether 869 women with breast cancer were randomized to receive WBI (439 patients) or observation (430 patients) in addition to their anti-hormonal therapy after breast-conserving surgery. All patients were defined as “low-risk” with node-negative grade 1 or 2 tumors less than 3 centimeters in size. Radiotherapy was given with conventional fractionation up to mean total doses of 50 Gray (Gy). Seventy-one percent of patients randomized to WBI also received an additional “tumor bed boost” with a mean dose of 10 Gy.
After a median follow-up of 9.89 years, there were 10 in-breast recurrences (IBR) in patients who had WBI and 31 among those who had anti-hormones only. Ten-year local control rates were 97.5 percent after radiotherapy compared with 92.4 percent in patients who did not have WBI. The disease-free survival (DFS) rate was significantly longer with radiation (94.5%) than without (88.4%). Looking at subgroups, there was also a significant advantage in DFS after WBI in patients who were treated with sentinel-node exstirpation only.
Both WBI and having the tumor grade not assessed (Gx grading) were detected as significant predictors for IBR. For the 519 patients in whom gene expression information was available, a biological high-risk group (those with Ki67 greater than 20 or who were positive for HER2/neu or who had both of these risk factors) nevertheless did not have significantly higher IBR rates.
The study concluded that after 10-years follow-up, WBI after BCS of hormonal receptor-positive “low-risk” breast cancer “maintained significantly better local control as well as DFS rates compared to anti-hormonal therapy alone.” The investigators also concluded that after sentinel-node exstirpation only, DFS was significantly improved after WBI, and the omission of WBI or having tumor Gx grading turned out to be the only negative predictors for IBR.
When asked whether adjuvant radiation should usually now be offered to treat low-risk breast cancer, Fastner said it should. “The irradiation therapy should only be omitted in elderly frail patients,” he said, adding that radiation was also recommended for patients with specific risk profiles who could be treated with partial breast irradiation using intra-operative or interstitial techniques. “You don't need to treat the whole breast but the partial breast.”
When discussing the overall survival, regional recurrence-free survival, and metastasis-free survival, Fastner was not surprised at the lack of significant differences between the patients who were irradiated or not. The benefit had only been significant for the local control and DFS, he said.
“We see that whole breast irradiation has a kind of impact on survival endpoints—not on overall, but on disease-free survival. And for overall survival, we should have longer follow-up for these patient groups because we know from the early breast cancer collaborative group that radiotherapy could be translated into an overall survival benefit after 15 years. So I think we should make another follow-up some time later,” he explained.
After his talk, Fastner was questioned by President of the European Cancer Organization Philip Poortmans, MD, PhD, from Institut Curie in Paris, about the possibility of omitting hormone therapy in some patients who could be recommended to use only adjuvant radiotherapy after their initial surgery. Fastner was reluctant to give commitment to such a policy. But he said that poor compliance in older patients should encourage cancer doctors to be sure to include radiation for them.
“There are no prospective randomized trials [that] investigated the omission of anti-hormonal treatment compared to radiotherapy alone and compared with radiotherapy together with anti-hormonal treatment,” noted Fastner. “But, if we look to the patient age, we know that the compliance of these patients to take anti-hormones is about 60 percent. So we know that about 30-40 percent do not take the anti-hormones anyway. So I think that whole breast irradiation seems necessary to preserve breasts.”
Peter M. Goodwin is a contributing writer.