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

Sep 28, 2026

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Purpose: Neurofibromatosis type 1 (NF1) is a rare autosomal dominant disorder linked to elevated cancer risk, including a fivefold higher incidence of breast cancer. Preclinical findings indicate increased radiosensitivity in NF1, but clinical evidence on long-term safety is limited. This retrospective single-center study evaluates long-term outcomes and treatment-related toxicities in NF1 patients receiving adjuvant radiation therapy for breast cancer.

LanguageEnglish

CategoryHealthcare

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Pages9

Reading Time23 min

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Purpose

Methods and Materials

Study design and patient selection

Results

Conclusions

Advances in Radiation Oncology (2026) 11, 101931 Scientiﬁc Article Adjuvant Radiation Therapy in Breast Cancer Patients With Neuroﬁbromatosis Type 1: Safety and Long-Term Outcomes Carla Benmatallah, MD,a,b Youlia Kirova, MD,a,b,c and Pierre Loap, MDa,b,c,d,e,* aDepartment of Radiation Oncology, Institut Curie, Paris, France; bIHU des Cancers des Femmes, ANR, 23-IAHU-0006, Paris, France; c Universit Versailles Saint Quentin (UVSQ), Versailles, France; dProton Therapy Center (CPO), Institut Curie, Orsay, France; and eLaboratoire d ’Imagerie Translationnelle en Oncologie (LITO), Institut Curie, Orsay, France Received 19 August 2025; accepted 10 October 2025 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.© 2025 The Authors. Published by Elsevier Inc. on behalf of American Society for Radiation Oncology. This is an open access article under the CC BY license ([http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/)). Introduction Neuroﬁbromatosis type 1 (NF1), or von Recklinghausen disease, is a rare autosomal dominant disorder Sources of support: This work had no speciﬁc funding. Research data are stored in an institutional repository and will be shared upon request to the corresponding author. *Corresponding author: Pierre Loap, MD; Email: pierre.loap@gmail. com affecting approximately 1 in 3000 live births. It results from inactivating mutations in the NF1 gene on chromosome 17, which encodes neuroﬁbromin, a tumor suppressor that negatively regulates RAS/MAPK signaling.1 Loss of neuroﬁbromin promotes uncontrolled cellular proliferation and tumor development. Individuals with NF1 have an increased predisposition to several malignancies, particularly malignant peripheral nerve sheath tumors,2-4 and face a 5-fold higher risk of breast cancer compared with the general population.5 [https://doi.org/10.1016/j.adro.2025.101931](https://doi.org/10.1016/j.adro.2025.101931) 2452-1094/© 2025 The Authors. Published by Elsevier Inc. on behalf of American Society for Radiation Oncology. This is an open access article under the CC BY license ([http://creativecommons

FAQs

Why is adjuvant radiation therapy safety a concern in NF1 breast cancer patients?

NF1 is associated with increased radiosensitivity suggested by preclinical data, raising concerns about acute and late radiation-induced toxicities and possible secondary malignancies. Clinical long-term data were previously lacking for this population.

How was the study conducted and what patient group was included?

The study is a retrospective single-center analysis of 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 using Kaplan-Meier survival estimates and CTCAE toxicity grading.

What were the key long-term findings on survival and toxicity?

After a median follow-up of 79 months, 10-year overall and cancer-specific survival were 68.3% each, with metastasis-free survival of 68.4%. Local and locoregional control exceeded 92%, acute radiodermatitis occurred in 83.3% (mostly grade 1–2), and no grade ≥3 acute or late toxicity, radiation-induced malignancy, or cardiopulmonary events were reported.

Sep 28, 2026

Uploaded by McQueen