Radiotherapy Not Linked to Increased Survival in Older Adults With Early Breast Cancer

Radiotherapy may not significantly prolong overall survival (OS) in older patients with early hormone receptor (HR)–positive breast cancer who received breast-conserving surgery and adjuvant endocrine therapy, according to a study published in the New England Journal of Medicine. Avoiding irradiation does not appear to significantly increase a patient’s risk of dying from breast cancer, the study found.

“Omission of radiotherapy was associated with an increased incidence of local recurrence

but had no detrimental effect on distant recurrence as the first event or OS,” the study authors wrote. “The applicability of these results to clinical practice will be influenced by the balance of the risks and benefits of radiation as compared with those of adjuvant endocrine therapy.”

Older patients with breast cancer are underrepresented in clinical trials, despite 26% of breast cancer diagnoses occurring in women aged 65 to 74 years, according to the study. There is conflicting evidence regarding the use of radiotherapy after breast-conserving therapy. This discussion extends into the population of low-risk, older patients with smaller HR–positive tumors, according to the study.

In the PRIME II phase 3 randomized clinical trial, investigators enrolled 1326 women aged 65 years and older with HR-positive smaller (T1 or T2) breast cancer and with a node-negative, estrogen receptor (ER)–positive tumor or progesterone receptor–positive tumor. An analysis of prior findings on the effects of irradiation on breast cancer recurrence at 5 years showed that it was associated with decreased local breast cancer recurrence; however, current guidelines support omitting it in certain populations of older women.

The current study examined the 10-year results of the PRIME II trial. The primary endpoint was local breast cancer recurrence, with secondary endpoints of regional recurrence, contralateral breast cancer, distant metastases, disease-free survival, and OS.

The team randomized the patients 1:1 in groups who did, and did not, receive postoperative radiotherapy. At the 10-year follow-up, OS in the radiotherapy and no-radiotherapy groups was 80.7% and 80.8%, respectively, cumulative incidence of local recurrence was 0.9% and 9.5%, respectively, disease-free survival was 68.9% and 76.3%, respectively, and cumulative incidence of distant recurrence as the first event was 3% and 1.6%, respectively.

In a subgroup analysis, investigators looked at ER-positive tumor status on cumulative incidence of local recurrence. Patients with an ER-high cancer had lower incidence of recurrence using radiotherapy, however, adherence to endocrine therapy may mitigate the risk of recurrence if they do not receive radiotherapy.

Trial limitations included that the data were not collected on coexisting conditions that a patient may have, nor did they monitor patient adherence to endocrine therapy. Additionally, investigators did not collect data on the toxic effects of radiotherapy, which has been linked to additional cancers and cardiac arrest.

“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,” the study authors wrote.

Reference

Kunkler I, Chir B, Williams L, et al. Breast-Conserving Surgery with or without Irradiation in Early Breast Cancer. N Engl J Med. 2023. DOI: 10.1056/NEJMoa2207586.