Adjuvant Radiation Therapy in Breast Cancer Patients With Neurofibromatosis Type 1: Safety and Long-Term Outcomes.

Purpose: Neurofibromatosis type 1 (NF1) is a rare autosomal dominant disorder associated with an increased risk of cancer, including a 5-fold higher incidence of breast cancer. Preclinical data suggest heightened radiosensitivity in NF1, raising concerns about toxicity and secondary malignancies after radiation therapy. Clinical data, however, are lacking. This study aimed to evaluate long-term outcomes and treatment-related toxicities in NF1 patients receiving adjuvant radiation therapy for breast cancer. Methods and Materials: This retrospective single-center study included 27 NF1 patients with nonmetastatic breast cancer treated with surgery and adjuvant radiation therapy between 1995 and 2023. Clinical, pathologic, treatment, and toxicity data were analyzed. Survival was assessed using Kaplan-Meier estimates, and toxicities were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events. Results: Among 27 patients (30 tumors), the median follow-up was 79 months. The 10-year overall and cancer-specific survival rates were 68.3% each, and the metastasis-free survival rate was 68.4%. Local and locoregional control exceeded 92%. Acute radiodermatitis occurred in 83.3% of patients (grade 1-2); no grade ≥ 3 acute or late toxicity was observed. Late toxicities were rare and mild. No radiation-induced malignancy or cardiopulmonary events were reported. Nodal involvement and lymphovascular invasion were significantly associated with poorer survival. Conclusions: Adjuvant radiation therapy is safe and effective in NF1 patients with breast cancer, despite a notably high incidence of low-grade acute skin toxicity. No serious long-term toxicity or radiation-induced malignancy was observed. Modern dose-sparing techniques should be prioritized, and further prospective studies are needed to refine treatment approaches in this high-risk group.