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Radiotherapy after breast-conserving surgery can be safely omitted in certain older women with low-risk, hormone receptor-positive early breast cancer receiving adjuvant endocrine therapy, 10-year results of the PRIME II trial showed.

In the randomized trial, the omission of post-surgery radiotherapy led to higher rates of local recurrence, but did not adversely affect distant recurrence or overall survival (OS), reported Ian Kunkler, MB, BChir, of the University of Edinburgh in Scotland, and colleagues in the .

Among more than 1,300 women 65 and up with node-negative tumors and clear surgical margins following surgery, the cumulative incidence of local breast cancer recurrence within 10 years was 9.5% for those randomized to no radiotherapy and 0.9% for those assigned to 40-50 Gy whole-breast radiotherapy (HR 10.4, 95% CI 4.1-26.1, P<0.001).

But distant recurrence and OS at 10 years were similar for the no-radiotherapy and radiotherapy groups:

• Distant recurrence: 1.6% vs 3.0%, respectively
• OS: 80.8% vs 80.7%

Kunkler's team called the absolute 8.6-percentage point difference in local recurrence between groups "modest" and noted that the cumulative incidence of local recurrence at 10 years in the patients who did not receive radiotherapy "lies within range from the European Society of Mastology (EUSOMA) guidelines, which cited a maximum rate of locoregional recurrence of 10% at 10 years."

Current National Comprehensive Cancer Network (NCCN) allow for the omission of radiation therapy after breast-conserving surgery in women ages 70 and older with stage I, estrogen receptor (ER)-positive breast cancer.

A post hoc subgroup analysis of PRIME II, based on ER score, showed that cumulative recurrence at 10 years in the no-radiotherapy group was far more common among women with ER-low tumors (19.1% vs 8.6% for ER-high).

Women in the no-radiotherapy arm who discontinued the recommended 5 years of endocrine therapy had a risk of local recurrence that was more than four times greater than those who stayed on therapy (HR 4.66, 95% CI 1.77-12.25).

These findings combined led Kunkler and co-authors to conclude that PRIME II "provides robust evidence" that radiation therapy can be safely omitted following breast-conserving therapy in older women with grade 1-2, ER-high tumors, "provided that they receive 5 years of adjuvant endocrine therapy."

Writing in an , Alice Ho, MD, of Duke University School of Medicine in Durham, North Carolina, and Jennifer Bellon, MD, of the Dana-Farber Cancer Institute in Boston, said the "data offer a response to the long-standing problem of overtreatment in older women with low-risk breast cancer."

Results from PRIME II, as well as from the Cancer and Leukemia Group B (CALGB) 9343 trial, can "put to rest" any doubt that omitting radiotherapy is possible in women 65 years and older with ER-positive, early-stage breast cancer, they added, pointing out that the 10-year follow-up from the trials is "extremely reassuring, given the long natural history of ER-positive breast cancer."

Ho and Bellon commented that the results of the trial don't weaken the value of radiotherapy in reinforcing local control, "which is a compelling endpoint in and of itself, particularly now that radiotherapy can be delivered in less burdensome ways."

"Individualizing the treatment so that it is concordant with the patient's goals and values is critical," they wrote. "Taken 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."

Women in PRIME II underwent 1:1 randomization from 2003 to 2009. Of the 1,326 patients in the study, the median age at trial entry was 70 years, and 1,263 were recruited from the U.K.

Patients included had hormone receptor-positive, node-negative, T1-2 primary breast tumors (3 cm or smaller) and needed to have clear excision margins following breast-conserving surgery. Five years of adjuvant endocrine therapy was recommended for all participants (20 mg tamoxifen daily), and adherence was between 60% and 70%.

Noting the higher rate of recurrence in the no-radiotherapy group among women who were nonadherent to tamoxifen, the editorialists said this finding "underscores the fact that endocrine therapy can have side effects, leading many to postulate that a short course of radiotherapy could be an alternative to endocrine therapy." They added that the is currently testing such a comparison in women 70 and older with early-stage, low-risk hormone receptor-positive disease.

PRIME II's primary endpoint was local breast cancer recurrence, while other endpoints such as disease-free survival, breast cancer-specific survival, distant recurrence, and OS were also assessed.

At 10 years, disease-free survival rates were 68.9% in the no-radiotherapy group and 76.3% in the radiotherapy group, while breast cancer-specific survival was 97.4% and 97.9%, respectively. No difference was seen in regional recurrence as well.

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