medwireNews: The 10-year data from the PRIME II trial suggest that radiotherapy after breast-conserving surgery can be omitted for women aged 65 years or older with low-risk, hormone receptor-positive early breast cancer.
Although the incidence of local recurrence was significantly higher among women who did not versus did undergo radiotherapy, this “had no detrimental effect on distant recurrence as the first event or overall survival,” note the researchers in The New England Journal of Medicine.
The authors of an accompanying editorial say that in light of these results and those of the CALGB 9343 trial addressing “the identical question” in patients aged at least 70 years, “[a]ny doubt that radiotherapy cannot be omitted in women 65 years of age or older with ER [estrogen receptor]-positive, early-stage breast cancer can be put to rest.”
Alice Ho (Duke University School of Medicine, Durham, North Carolina, USA) and Jennifer Bellon (Harvard Medical School, Boston, Massachusetts, USA) continue: “The 10-year follow-up [data from] the trials are extremely reassuring, given the long natural history of ER–positive breast cancer.”
The editorialists point out, however, that “[t]hese results do not undermine the value of radiotherapy in enhancing local control, which is a compelling end point in and of itself, particularly now that radiotherapy can be delivered in less burdensome ways.”
And they believe that “[t]aken together, these data will help patients navigate these complex choices so that they can make well-informed and prudent decisions for the management of their breast cancer.”
The phase 3 randomized PRIME II study enrolled 1326 women aged 65 years or over with hormone receptor-positive, node-negative T1 or T2 tumors (≤3 cm in the largest dimension) treated with breast-conserving surgery and adjuvant endocrine therapy.
The cumulative incidence at 10 years of the primary endpoint of local recurrence was 9.5% among the 668 participants who did not receive adjuvant whole-breast irradiation and 0.9% among the 658 who did, a significant difference equating to a hazard ratio (HR) of 10.4.
However, the 10-year cumulative incidence of distant recurrence as the first event was similar without and with radiotherapy, at 1.6% and 3.0%, respectively, report Ian Kunkler, from the University of Edinburgh in the UK, and co-investigators.
They add that the 10-year breast cancer-specific survival rates were comparable and overall survival rates were “almost identical” without and with whole-breast irradiation, at 97.4% versus 97.9% and 80.8% versus 80.7%, respectively.
The commentators note that around 90% of both treatment groups had ER-high disease “which constrains the applicability of the data to patients with moderately ER-positive disease.”
But post-hoc subgroup analysis by ER status supported earlier research indicating that there was a lower 10-year cumulative incidence of local recurrence among participants with ER-high versus low tumors, with respective rates in the no radiotherapy group of 8.6% and 19.1%.
And a time-dependent analysis revealed an increased risk for local recurrence in the no radiotherapy group for women who discontinued endocrine therapy compared with their counterparts who did not (HR=4.66).
Kunkler and colleagues conclude: “Our trial provides robust evidence indicating that irradiation can be safely omitted in women 65 years of age or older who have grade 1 or 2, ER-high cancers treated by breast-conserving therapy, provided that they receive 5 years of adjuvant endocrine therapy.”
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