Omitting postoperative radiotherapy with whole-breast irradiation may not compromise 10-year overall survival or increase the risk of developing metastasis in most women 65 years and older with low-risk breast cancer, according to results of the large randomized PRIME II trial reported at the 2020 San Antonio Breast Cancer Symposium.1
At 10 years after primary treatment with breast-conserving surgery and adjuvant endocrine therapy, the rate of ipsilateral breast tumor recurrence was 9.8% in older women with low-risk breast cancer who did not have radiotherapy and 0.9 % in those who received radiotherapy as initial treatment. Although this difference in local recurrence was statistically significant (P = .000008), it did not translate to improved survival and metastases outcomes.
“We recognize there is a small risk of local recurrence when you omit postoperative radiation, but there is no compromise in mortality.”— Ian H. Kunkler, MB, BChir, MA, FRCR
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“We would recommend the omission of postoperative radiotherapy as a reasonable option for women with pT1–2 [≤ 3 cm] grade 1 or 2 tumors, as there is no evidence that it increases the risk of metastatic disease nor impacts survival. Most deaths in this population were not due to breast cancer,” said lead author Ian H. Kunkler, MB, BChir, MA, FRCR, Consultant Clinical Oncologist and Professor of Clinical Oncology at MRC Institute of Genetics & Molecular Medicine, Cancer Research UK Edinburgh Centre, Scotland.
“I hope I have provided reassuring data,” Dr. Kunkler noted. “We recognize there is a small risk of local recurrence when you omit postoperative radiation, but there is no compromise in mortality.”
There is sparse level 1 evidence on the impact on local control and quality of life in older, low-risk women treated with postoperative radiotherapy after breast-conserving surgery and adjuvant endocrine therapy. Results from the PRIME I trial showed that postoperative radiotherapy was well tolerated and did not seem to impair quality of life.2 The CALGB 9343 trial found that in low-risk patients, breast-conserving surgery plus tamoxifen with or without whole-breast irradiation resulted in a 10-year local recurrence rate of 2% with radiotherapy and 9% without it.3
“We would recommend caution in omitting whole-breast irradiation in patients with low estrogen receptor–positive tumors.”— Ian H. Kunkler, MB, BChir, MA, FRCR
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The 5-year results from PRIME II, with a similar design to CALGB 9343, found that radiotherapy significantly reduced the risk of local recurrence from 4.1% with no radiotherapy to 1.3% in older low-risk women (P = .0002).4 “Radiotherapy significantly reduced the risk of recurrence in the 5-year analysis of PRIME II, but a 2.8% absolute reduction is relatively modest,” Dr. Kunkler pointed out.
The aim of the present study was to look at the effect of omitting whole-breast irradiation after breast-conserving surgery and adjuvant endocrine therapy on local tumor control at 10 years in older, low-risk patients. Data were locked on May 28, 2020.
The study enrolled women aged 65 and older with histologically confirmed unilateral invasive breast cancer and a tumor size of up to 3 cm. All women underwent breast-conserving surgery and were found to have node-negative disease.
Over 6 years, 1,326 women were recruited: 658 received whole-breast irradiation and 668 did not. Radiotherapy was given as 40 to 50 Gy in 15 to 25 fractions. At baseline, both groups were comparable for median age (about 71) as well as tumor size, grade, and use of preoperative endocrine therapy.
“The majority of patients had tumors smaller than 20 mm. More than 95% had grade 1 or 2 tumors. Only a small proportion had lymphovascular invasion, and a minority had grade 3 tumors,” he said.
Radiotherapy reduced the 10-year rate of actuarial ipsilateral breast tumor recurrence from 9.8% to 0.9% (P = .00008). There was a small increase in regional recurrence without whole-breast irradiation: 2.3% vs 0.5% with radiotherapy (P = .014). However, there were no differences between treatment arms in terms of distant recurrence, contralateral breast recurrence, and new cancer (not breast cancer).
Of note, there was no survival difference when whole-breast irradiation was omitted. The 10-year actuarial overall survival rate was 80.4% without and 81% with whole-breast irradiation. A similar pattern was observed in 10-year metastasis-free survival: 98.1% without vs 96.4% with whole-breast irradiation.
Deaths from cancer were reported in 39% of the group that did not receive irradiation and 37% of those who received whole-breast irradiation. The breast cancer–specific death rate was 9% without and 4% with whole-breast irradiation.
In an unplanned subgroup analysis according to estrogen receptor status in those who did not receive whole-breast irradiation, women who had tumors with a low estrogen receptor status experienced a much higher local recurrence rate at 10 years compared with those who had a high estrogen receptor status: 18.8% vs 9.2% (P = .007).
“This finding is from an exploratory analysis and requires confirmation in a randomized trial,” noted Dr. Kunkler. “However, we would recommend caution in omitting whole-breast irradiation in patients with low estrogen receptor–positive tumors.”
Dr Kunkler concluded that the omission of postoperative radiotherapy is a reasonable option for pT1–2 (≤ 3 cm) grade 1–2 tumors after breast-conserving surgery and adjuvant endocrine therapy in women aged ≥ 65 years, as there is no evidence that it increases the risk of metastatic disease or impacts survival.
DISCLOSURE: Dr. Kunkler reported no conflicts of interest.
1. Kunkler IH, Williams LJ, Jack W, et al: PRIME II randomised trial (postoperative radiotherapy in minimum-risk elderly): Wide local excision and adjuvant hormonal therapy whole breast irradiation in women ≥ 65 years with early invasive cancer: 10-year results. 2020 San Antonio Breast Cancer Symposium. GS2-03. Presented December 9, 2020.
2. Prescott RJ, Kunkler IH, Williams LJ, et al: A randomised controlled trial of postoperative radiotherapy following breast-conserving surgery in a minimum-risk older population: The PRIME trial. Health Technol Assess 11:1-149, 2007.
3. Hughes KS, Schnaper LA, Bellon JR, et al: Lumpectomy plus tamoxifen with or without radiation in women age 70 years or older with early breast cancer: Long-term follow-up of CALGB 9343. J Clin Oncol 31:2382-2387, 2013.
4. Kunkler IH, Williams LJ, Jack WJL, et al: Breast-conserving surgery with or without radiation in women aged 65 years or older with early breast cancer (PRIME II): A randomised controlled trial. Lancet Oncol 16:266-273, 2015.
Alphonse G. Taghian, MD, Professor at Harvard Medical School and Co-Director of Breast Cancer Research Program at Massachusetts General Hospital, Boston, said that these results from the PRIME II trial are quite similar to those of the older CALGB study first initiated in 1994.1 Both studies had a ...