The study, known as PRIME II, demonstrated a modest but statistically significant reduction in cancer recurrence in women who received radiotherapy, compared with those who did not. However, 5-year overall survival was similar in the two groups.
The results were published online January 28 in the Lancet Oncology.
“I think the PRIME II trial may be a practice-changing ‘tipping point’ in considering the omission of radiotherapy in selected older patients after breast-conserving surgery and adjuvant endocrine therapy. The omission of postoperative radiotherapy does not compromise survival,” said first author Ian Kunkler, FRCR, from the Edinburgh Cancer Research Center, West General Hospital, Scotland, United Kingdom.
Currently, the standard of care for all breast cancer patients in the United Kingdom is breast-conservation surgery and adjuvant endocrine therapy followed by whole-breast radiation, according to Dr Kunkler.
“Candidate patients for omission of radiotherapy would be those with grade 1 or 2 hormone-receptor-positive tumors up to 3 cm, axillary node-negative after breast-conserving surgery with clear margins, and receiving adjuvant endocrine therapy,” he added.
The possibility of radiation should not be excluded for all patients who meet these criteria, but skipping radiotherapy might be an option to discuss. “Some patients may still wish to have radiotherapy and accept the risks of toxicity, despite the modest reduction in risk of local recurrence from radiotherapy,” he explained.
The study contained too few patients with grade 3 tumors to reach conclusions on the safety of skipping radiotherapy in this group.
“This subgroup should continue to receive radiotherapy as standard,” Dr Kunkler stated. He added that there are plans for a 10-year follow-up.
In an accompanying comment, Kevin Hughes, MD, codirector of the Avon Comprehensive Breast Evaluation Center at Massachusetts General Hospital in Boston, and Lauren Schnaper, MD, from the Greater Baltimore Medical Center, take that a step further. They suggest skipping radiotherapy in all women who meet the eligibility requirements of this study.
This approach needs to become standard practice.
“The take-home message of this study is that women with node-negative, hormone-responsive breast cancers that are under 3 cm can be treated with lumpectomy plus hormonal therapy safely, without the need for radiation. This approach needs to become standard practice,” said Dr Hughes.
The added morbidity associated with radiotherapy and financial considerations are other concerns.
“The small benefit in local recurrence is not worth the cost and inconvenience of radiation in older women,” Dr Hughes explained.
“High-quality medical care must be objectively proven. In the population studied, the cost of radiation is not justified,” he added. “We should treat breast cancer in the most effective and least costly way possible, and use the money saved to manage other major healthcare issues.”
PRIME II Trial Details
The study was conducted from April 2003 to December 2009 in 76 centers. Overall, the cohort consisted of 16 patients from Australia, 22 from Greece, 25 from Serbia, and 1263 from the United Kingdom. The women were 65 years and older (mean age, 70 years), had undergone breast-conservation surgery, and were receiving adjuvant endocrine therapy. Their tumors were hormone-receptor positive, axillary node-negative, grade 1 or 2 up to 3 cm, and had clear margins. Women with grade 3 tumors or lymphovascular invasion, but not both, were included. Participants were followed for about 5 years.
Dr Kunkler and colleagues randomly assigned 658 women to whole-breast radiation (40 to 50 Gy in 15 to 25 fractions over 3 to 5 weeks) and 668 women to no radiotherapy. The standard endocrine therapy was tamoxifen, although other endocrine therapies were allowed.
The rate of cancer recurrence in the same breast was significantly lower in the women treated with radiotherapy than in those who were not (1.3% vs 4.1%; P = .0002). The absolute risk reduction for tumor recurrence in the same breast at 5 years was 2.9% (95% confidence interval [CI], 1.1 – 4.8).
There was no difference between the two groups in the rate of regional recurrence, distant metastases, cancer in the opposite breast, or new breast cancers.
Overall 5-year survival was 93.9% in both groups (95% CI, 91.8 – 96.0; P = .34). At 5 years, breast cancer-free survival was 97.6% (95% CI, 96.2 – 99.0) in women who received radiotherapy and 94.5% (95% CI, 92.5 – 96.5) in women who did not. The researchers attribute this difference to cancer recurrence in the same breast.
During the study period, 89 deaths occurred. In the group that received radiotherapy, four (10%) of the 40 deaths were due to breast cancer. In the group that did not receive radiotherapy, eight (16%) of the 49 deaths were due to breast cancer.
Dr Kunkler, Dr Hughes, and Dr Schnaper have disclosed no relevant financial relationships.