A more conservative approach that avoids radiation therapy seems to be a reasonable option for a subgroup of older women with hormone receptor–positive breast cancer at low risk of recurrence. Overall outcomes were similar with or without radiation in older women with hormone receptor–positive breast cancer in the PRIME II trial. Results suggest that radiation can be safely omitted in women whose tumors have high levels of estrogen receptor expression, according to a presentation at the 2013 San Antonio Breast Cancer Symposium.¹

“Postoperative radiation remains the standard of care for early breast cancer treated with breast-conserving surgery, irrespective of factors such as age. Older patients represent about 50% of all newly diagnosed early breast cancer, and these cancers are often relatively benign. Radiotherapy may represent overtreatment, and it is associated with risks. Also there is sparse level I evidence for radiation in older women,” said lead author, Ian Kunkler, FRCR, Edinburgh Cancer Research Center, University of Edinburgh, Scotland, UK. “Our study shows that the proportion of women who will have a local recurrence without radiation is very small—under 5%.”

Study Details

The multicenter PRIME II trial was conducted at 98 sites across six countries. The trial included 1,326 medically fit patients aged 65 or older with hormone receptor–positive, node-negative, T1–2 breast cancer (up to 3 cm), clear surgical margins, and treated with adjuvant endocrine therapy. All patients had clear surgical margins of at least 1 mm. Either grade 3 tumors or lymphovascular invasion was allowed (but not both). Patients were randomly assigned to receive whole-breast irradiation (n = 658) at 40 to 50 Gy or no whole-breast irradiation (n = 668).

The difference in 5-year ipsilateral breast cancer recurrence favored radiotherapy—6 recurrences (1.3%) with whole-breast irradiation vs 26 recurrences (4.1%) with no whole-breast irradiation (P = .002)—but Dr. Kunkler noted that the absolute difference of 2.8% was very small. Five-year overall survival was 94.2% for whole-breast irradiation vs 93.8% for no whole-breast irradiation, for an even smaller absolute difference of 0.4% (P = .24).

An unplanned exploratory analysis of the effect of estrogen receptor status on local recurrence showed that high levels of estrogen receptor expression (Allred score 7/8) were associated with a very modest gain in local control (2.4%) in women treated with whole breast irradiation compared to those in whom it was omitted (0.8% vs 3.2%, respectively, P = .003). Among those with low levels of estrogen receptor expression (Allred score 2–6), the local recurrence rates were 11.1% without radiotherapy vs 0 with radiotherapy (P = .025).

In a multivariate analysis, both no radiotherapy and low estrogen receptor expression were significantly associated with recurrence.

These results suggest that postoperative whole-breast irradiation can be safely omitted in some women aged 65 or older with node-negative, hormone receptor–positive breast cancer, tumors measuring up to 3 cm, and high estrogen receptor expression.

“However, the data suggest that radiation can not be safely omitted in women whose tumors have low estrogen receptor expression,” Dr. Kunkler clarified.

‘Broadly Generalizable’ Findings

“These results are broadly generalizable. This study is very likely to change practice within the United Kingdom. Older patients find radiotherapy burdensome. 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. Our results imply that quite a large group of women can benefit from the omission of radiotherapy,” Dr. Kunkler stated.”

All patients in PRIME II received hormonal therapy and breast-conserving surgery as part of management. During the question-and-answer session after the presentation, Steven Vogl, MD, a medical oncologist in the Bronx, New York, said that compliance with hormone therapy is important, and there was no way to know whether patients were actually taking their hormone therapy from the data presented. Dr. Kunkler said those data were not yet analyzed but would be included in the journal publication of the study. ■

Disclosure: This study was funded by the Chief Scientist’s Office for Scotland. Dr. Kunkler declared no potential conflicts of interest.

Reference

1. Kunkler IH, Williams LW, Jack W, et al: The PRIME II trial: Wide local excision and adjuvant hormonal therapy ± postoperative whole breast irradiation in women ≥ 65 years with early breast cancer managed by breast conservation. 2013 San Antonio Breast Cancer Symposium. Abstract S2-01. Presented December 11, 2013.