Skipping whole-breast adjuvant radiotherapy does not appear to affect long-term survival in women age 65 and older who have had surgery for early-stage, hormone receptor–positive (HR+) breast cancer, according to 10-year follow-up of the phase 3 PRIME-2 study.
Dr. Ian Kunkler
Although the risk for local recurrence was higher among patients who did not receive radiotherapy, the absolute risk for recurrence was still low, said study investigator Ian Kunkler, MRCPUK, FRCR, of Western General Hospital, University of Edinburgh in Scotland.
Dr. Kunkler presented results from PRIME-2 at the 2020 San Antonio Breast Cancer Symposium.
“In older patients, we have to carefully balance benefits [of radiotherapy] in terms of local control and survival against toxicities,” Dr. Kunkler said in an interview.
Omitting radiotherapy could help women avoid complications such as fatigue, changes to lung function, and an increased risk of cardiovascular damage.
“We think that these results should provide some reassurance that the omission of radiotherapy could be an option,” Dr. Kunkler said.
PRIME-2 results
The PRIME-2 study was a randomized trial that recruited 1,326 women with histologically confirmed, unilateral invasive breast cancer who were all 65 years or older.
For inclusion, the women had to have a tumor measuring 3 cm or less, have no nodal involvement, and be about to undergo breast-conserving surgery. Women also needed to be HR+ and be treated with adjuvant endocrine therapy.
The women were randomized 1:1 to receive adjuvant whole-breast irradiation at a dosing schedule of 40-50 Gy in 15-25 fractions or no radiotherapy in addition to adjuvant endocrine therapy.
The primary endpoint was the recurrence of breast cancer in the same breast at 10 years. There was a significantly lower rate of ipsilateral recurrence with radiotherapy than without it, at 0.9% and 9.8%, respectively (P = .00008).
Similarly, the 10-year rate of regional recurrence was significantly lower in the radiotherapy arm than in the no-radiotherapy arm (0.5% vs. 2.3%, P = .014).
However, there was no significant difference in the radiotherapy and nonradiotherapy arms when it came to distant recurrence (3.6% vs. 1.9%, P = .07), contralateral recurrence (2.2% vs. 1.2%, P = .20), or new, non–breast cancer (8.7% vs. 10.2%, P = .41).
The overall survival estimate at 10 years was 80.4% in women who did not receive radiotherapy and 81.0% in those who did (P = .68). Rates of metastasis-free survival were also similar (98.1% vs. 96.4%, P = .28).
“Most of these women are dying from non–breast cancer causes, reflecting the impact of competitive causes of non–breast cancer mortality,” Dr. Kunkler said.
Implications for practice
The current findings build on prior findings from the PRIME-2 study 5 years ago, which showed a small benefit of postoperative radiotherapy over no radiotherapy in reducing the rate of local recurrence. This led to the recommendation that postoperative radiotherapy might be safely omitted in some older women and influenced U.K. practice.
Indeed, Dr. Kunkler observed that U.K. guidelines have pretty much adopted the entry criteria for the PRIME-2 study (HR+, axillary node-negative [N0], T1–T2 up to 3 cm at the longest dimension, and clear margins) for the omission of radiotherapy.
“It’s had much less impact in the United States, where the usage of radiotherapy after breast-conserving surgery still remains very high,” Dr. Kunkler said.
He acknowledged that the current U.S. guidelines include the omission of radiotherapy in older women, but only those with much smaller (T1, N0) tumors, based on the findings of the Cancer and Leukemia Group B (CALGB) 9343 study.
“The findings from PRIME-2 so far seem consistent with long-term findings from CALGB 9343,” Matthew Katz, MD, of Lowell (Mass.) General Hospital Cancer Center, said in an interview.
Dr. Matthew Katz
However, “the median follow-up of the study was only 7 years, so it’s a little early to analyze 10-year data,” he added.
As to why leaving out radiotherapy in older women may be less common in the United States than in the U.K., Dr. Katz said it was probably due to a “tendency on the part of U.S. oncologists and cancer patients to lean more toward treatment to lower the risk of recurrence.
“When I discuss omitting radiation to women 70 or older with an early-stage, low risk breast cancer, the majority of people I see choose treatment,” he said. “The key is that a cancer patient can make informed choices about treatment based upon her or his values, looking at both the risks of cancer recurrence and the side effects of cancer treatments.”
“The decision as to whether radiotherapy is omitted or not has become a bit more nuanced,” since the PRIME-2 study started in 2003, Dr. Kunkler acknowledged.
He said there’s now evidence to suggest that shorter radiotherapy regimens may be beneficial. For example, the FAST-Forward trial showed that a regimen of 26 Gy in five fractions over 1 week was noninferior to a regimen of 40 Gy in 15 fractions over 3 weeks.
“There are really only two studies – the PRIME-2 study and the CALGB 9343 study – which are specific to an older age group,” Dr. Kunkler noted. “Most of the previous studies of breast-conserving surgery with or without radiotherapy receiving endocrine therapy have been predominantly in women under the age of 70. And indeed, 70 was often considered an exclusion criterion for randomized trials.”
PRIME-2 was funded by the Chief Scientist Office (Scottish Government) and the Breast Cancer Institute at the Western General Hospital in Edinburgh, Scotland. Neither Dr. Kunkler nor Dr. Katz had relevant disclosures.
SOURCE: Kunkler IH J et al. SABCS 2020, Abstract GS2-03.