If treated with hormonal therapy and considered to be at low risk for breast cancer recurrence, women aged 65 and older with hormone receptor-positive, axillary node-negative breast cancer may be able to forego radiation therapy (RT) after breast conserving surgery.
Photo Courtesy © SABCS/Todd Buchanan 2013
Ian Kunkler, FRCR
If treated with hormonal therapy and considered to be at low risk for breast cancer recurrence, women aged 65 and older with hormone receptor-positive, axillary node-negative breast cancer may be able to forego radiation therapy (RT) after breast conserving surgery. In the international phase III PRIME 2 trial presented at the 2013 San Antonio Breast Cancer Symposium (SABCS), results were even more convincing in women with high estrogen receptor (ER) expression versus low ER expression.
“Radiotherapy has been known to reduce the risk of breast cancer recurrence three- to fourfold. However, our trial has shown that although this is the case, the proportion of women who actually will have a recurrence without radiotherapy is very small (< 5%) 5 years after treatment,” said Ian Kunkler, FRCR, professor of clinical oncology, Edinburgh Cancer Research Center, University of Edinburgh, Scotland, United Kingdom. “We have identified a subgroup of older patients at sufficiently low risk of recurrence for whom omission of postoperative radiotherapy after breast-conserving surgery and adjuvant endocrine therapy is a reasonable option.”
PRIME 2 randomized 1326 patients aged 65 or older with hormone receptor-positive, node-negative, T1-2 breast cancer (up to 3 cm) were evenly divided to receive adjuvant RT or none. All patients had clear surgical margins of at least 1 mm, and were receiving adjuvant endocrine therapy. Either grade 3 tumors or lymphovascular invasion was allowed, but not both.
Although the difference in 5-year ipsilateral breast tumor recurrence favored RT (26 patients [4.1%] had recurrence with no RT versus 6 [1.3%] who received RT, the absolute difference was very small. Five-year overall survival was 93.8% with no RT versus 94.2% in patients who had it.
Investigators also examined the effect of ER-status on local recurrence. The local recurrence rate in patients whose tumors had high ER expression was 3.2% with no RT versus 0.8% with it (P= .003); low ER expression was associated with an 11.1% recurrence rate without radiotherapy and 0% with radiotherapy (P= .015).
Of 89 deaths across both groups, the majority (73%) were not linked to breast cancer. Of the 12 deaths attributed to breast cancer, four patients received postoperative RT and eight did not.
These results suggest that postoperative whole-breast radiation can be safely omitted in women aged 65 or older with node-negative breast cancer and tumors up to 3 cm, Kunkler said. He added that foregoing radiation is especially reasonable in women whose tumors have high ER expression.
“For every 100 women [from our selected population] treated with radiotherapy, one will have a recurrence anyway, four will have a recurrence prevented, but 95 will have had unnecessary radiotherapy,” Kunkler explained. “Once a patient has radiotherapy, she is unable to have it again on the same breast. If these women had not had radiotherapy, they would have been able to have minor surgery and radiotherapy at recurrence. Besides, radiotherapy has its own health risks, particularly in the elderly, as well as the inconvenience of travel for daily treatment over 3 or 4 weeks.”
Kunkler IH, Williams LW, Jack W, Canney P, Prescott RJ, Dixon MJ. The PRIME 2 trial: Wide local excision and adjuvant hormonal therapy ± postoperative whole breast irradiation in women ≥65 years with early breast cancer managed by breast conservation. Presented at: the 36th Annual San Antonio Breast Cancer Symposium; December 10-14, 2013; San Antonio, TX. Abstract S2-01.