Omitting radiation therapy after breast-conserving surgery may not impact long-term survival rates for older patients with hormone receptor (HR)-positive breast cancer. Patients who do not receive radiation therapy may have higher rates of local recurrence, but they have similar 10-year survival rates when compared to patients who received postoperative radiation therapy, according to a new study.
Evidence is limited on the long-term outcomes after loco-regional radiotherapy following breast-conserving surgery in older patients when they are also receiving appropriate systemic therapy. Despite the less-aggressive breast cancers typically diagnosed in this population, most patients who undergo breast-conserving surgery continue to be treated with whole breast radiation therapy after surgery.
"Over half the patients diagnosed with breast cancer in developed countries are over the age of 65 years," said lead author Ian Kunkler, FRCPE, Professor of Clinical Oncology at the Western General Hospital, University of Edinburgh. "We were interested in determining whether older patients with low-risk breast cancer could be spared radiation therapy."
Study Details
At the 2020 San Antonio Breast Cancer Symposium, Kunkler presented a 10-year update of results from the PRIME II study (Abstract GS2-03). This international, Phase III, randomized, controlled trial enrolled 1,326 patients with non-metastatic HR-positive breast cancer. All patients were at least 65 years old, had undergone breast-conserving surgery, and were receiving adjuvant hormone therapy. Patients were eligible if they had grade 3 tumors or lymphovascular invasion, but not both. Patients were randomly assigned to either receive (658 patients) or not receive (668 patients) radiation therapy after surgery.
Previously, Kunkler and colleagues reported greater rates of local recurrence, defined as recurrence in the same breast as the primary tumor, in patients who did not receive radiation therapy, but no significant differences in overall survival, distant metastases, or new breast cancers between the two arms after 5 years. In the new study, Kunkler reported that the rate of local recurrence after 10 years was significantly greater in patients who did not receive radiation therapy (9.8%) compared with patients who did (0.9%). While postoperative radiation therapy affected the risk of local recurrence, it did not significantly impact certain other clinical outcomes.
After 10 years, significant differences were found in regional recurrence (2.3% no radiotherapy vs. 0.5% with radiotherapy), but those who did not receive radiation therapy had similar rates of distant metastasis (1.4% vs. 3.6%), recurrence in the opposite breast (1% vs. 2.2%), and overall survival (80.4% vs. 81%) as patients who did receive radiation therapy. Most deaths were due to reasons other than breast cancer.
Breast cancer-free survival was 12.7 percent for the no radiotherapy arm and 6.6 percent for the radiotherapy arm. Breast-specific survival was similar: no radiotherapy 98.2 percent versus 97.8 percent with radiotherapy.
"We found that omitting postoperative radiation therapy did not compromise survival or increase the risk of distant metastasis," said Kunkler. "Based on these results, we believe that omission of radiation therapy after breast-conserving surgery should be an option for older patients with localized, HR-positive breast cancer who are receiving adjuvant hormone therapy and meet certain clinico-pathological criteria."
One limitation of the study is that only a few patients with grade 3 tumors were recruited, so the study results may not be applicable to patients with high-grade tumors or with tumors larger than 3 centimeters. An additional limitation is that data on comorbidities or adherence to adjuvant hormone therapy were not collected.
In conclusion, Kunkler said: "Ten-year follow-up data from the PRIME 2 trial shows that the omission of radiotherapy after BCS in women aged 65 years and older with T1-2, pN0 HR-positive breast cancer results in only 9.8 percent ipsilateral breast tumor recurrence. While this rate is significantly reduced by radiotherapy, the absolute reduction is modest, and there were no differences in the secondary endpoints of distant metastases, contralateral breast cancer, or overall survival and a small but significant difference in regional recurrence.
"These data suggest that postoperative radiotherapy in this patient group who are receiving adjuvant hormonal therapy does not impact on overall survival in the context of modern approaches to local and systemic adjuvant therapy, with most patients in both arms dying of causes unrelated to breast cancer or its treatment."
Mark L. Fuerst is a contributing writer.