Disease-free survival improved with neoadjuvant radiotherapy in early-stage breast cancer

For women with early-stage breast cancer, neoadjuvant radiotherapy (RT) may significantly improve disease-free survival, with no reduction in overall survival, particularly in those with estrogen receptor-positive cancers, according to a recent study published in the journal Breast Cancer Research.

A number of recent studies have suggested that radiation therapy may re-educate and stimulate the immune system to target cancer cells.

“The observed benefit of neoadjuvant radiation therapy aligns with the growing body of literature of the immune activation effects of radiation, including shrinking of untreated metastases outside the radiation field,” explained senior author Heiko Enderling, PhD, associate member of Moffitt’s Integrated Mathematical Oncology Department.

Postoperative adjuvant RT has been shown to improve relapse-free survival in patients with early-stage breast cancer, but the effects of neoadjuvant versus adjuvant RT in these patients is not known. To assess this, researchers from Moffitt Cancer Center conducted this study.

They used data from the Surveillance, Epidemiology, and End Results database from the National Institutes of Health to derive an analytic dataset of 250,195 female early-breast cancer patients who underwent RT before (n=2,554; 1.02%) or after (n=247,641; 98.98%) surgery. From automated patient identification matching of all SEER records, they calculated disease-free survival, which they defined as time to diagnosis of a second primary tumor at any location.

In all, 94.4% of patients underwent partial mastectomy and 5.6% underwent complete mastectomy. In the largest cohort of estrogen receptor-positive women undergoing partial mastectomy, the hazard ratio (HR) of developing a second primary tumor after neoadjuvant therapy compared with adjuvant RT was 0.64 (95% CI: 0.55-0.75; P < 0.0001). 

Researchers found that overall survival was independent of radiation sequence (HR: 1: P=0.95). They also observed that estrogen receptor-positive patients undergoing neoadjuvant RT had a lower HR for a second primary cancer after mastectomy, compared with patients who were treated with adjuvant RT (HR: 0.48; 95% CI: 0.26-0.87; P=0.0162).

“Historic data indicate that disease-free survival is significantly increased when radiation therapy is applied before surgery rather than after surgery, especially for ER-positive patients. These findings are worthy of a prospective clinical trial to confirm potential benefits of neoadjuvant vs adjuvant radiation, and to identify the potential contribution of radiation-induced immunity to vaccinate against future disease,” said Dr. Enderling.

This study was supported by funds received from the American Cancer Society and the DeBartolo Family Personalized Medicine Institute Pilot Research Awards in Personalized Medicine.