Neoadjuvant radiotherapy of early-stage breast cancer and long-term disease-free survival

Background: Compared with surgery alone, postoperative adjuvant radiotherapy (RT) improves relapse-free survival of patients with early-stage breast cancer. We evaluated the long-term overall and disease-free survival rates of neoadjuvant (presurgical) versus adjuvant RT in early-stage breast cancer patients.

Methods: We used the Surveillance, Epidemiology, and End Results (SEER) database provided by the National Institutes of Health to derive an analytic dataset of 250,195 female patients with early-stage breast cancer who received RT before (n = 2554; 1.02%) or after (n = 247,641; 98.98%) surgery. Disease-free survival, defined as time to diagnosis of a second primary tumor at any location, was calculated from automated patient identification matching of all SEER records.

Results: Partial and complete mastectomies were performed in 94.4% and 5.6% of patients, respectively. In the largest cohort of estrogen receptor-positive women who underwent partial mastectomy, the HR of developing a second primary tumor after neoadjuvant compared with adjuvant RT was 0.64 (95% CI 0.55-0.75; P < 0.0001). Overall survival was independent of radiation sequence (HR 1; P = 0.95). Neoadjuvant RT also resulted in a lower HR for second primary cancer among estrogen receptor-positive patients who underwent mastectomy compared with those who received adjuvant RT (HR 0.48, 95% CI 0.26-0.87; P = 0.0162).

Conclusions: Neoadjuvant RT may significantly improve disease-free survival without reducing overall survival, especially for estrogen receptor-positive patients with early-stage breast cancer. This finding warrants further exploration of potential long-term benefits of neoadjuvant radiotherapy for early-stage breast cancer in a controlled, prospective clinical trial setting, with correlative studies done to identify potential mechanisms of superiority.