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. 2025 Jul 17;134:111698. doi: 10.1016/j.ijscr.2025.111698

Surgical and radiation considerations in breast cancer with neurofibromatosis type 1: A case report and literature review

Kenichiro Tanaka a,⁎, Masami Arai b, Shunsuke Sakuraba a, Tomoyuki Kushida a, Tomoaki Ito a, Goro Kutomi c
PMCID: PMC12301899  PMID: 40690820

Abstract

Introduction and importance

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder that predisposes individuals to skin pigmentation changes and nerve tissue tumors, with an incidence of 1 in 2500. NF1 is associated with various malignancies, including breast cancer. This is a rare case of breast cancer with NF1 who chose breast-conserving surgery (BCS) and radiotherapy.

Presentation of case

A 66-year-old NF1 patient with breast cancer underwent partial mastectomy, sentinel lymph node biopsy, and radiotherapy (40.5 Gy). Chemotherapy was recommended but the patient opted for adjuvant endocrine therapy. No recurrence or sarcoma formation was observed over two years post-treatment.

Clinical discussion

In breast cancer cases, decisions between mastectomy and BCS are critical. Radiotherapy is an essential component following BCS. The risk of post-radiotherapy sarcoma formation is higher in NF1 patients, complicating the choice of BCS in this group.

Conclusion

This case highlights the complexities of treatment decisions, including increased sarcoma risk from radiation in NF1 patients.

Keywords: Neurofibromatosis type I, Breast cancer, Surgery, Radiotherapy, Case report

Highlights

  • •

    Neurofibromatosis 1 is often associated with malignancies, including breast cancer

  • •

    In breast cancer, choosing between mastectomy and breast-conserving surgery (BCS) is critical, as BCS requires radiotherapy

  • •

    In NF1 patients, radiotherapy is not absolutely contraindicated, but its sarcoma risk complicates BCS decisions

1. Introduction

Neurofibromatosis type 1 is an autosomal dominant genetic disorder characterized by skin pigmentation and nerve tissue tumors, with an incidence of approximately 1 in 2500 individuals [1]. NF1 is usually caused by various types and locations of disorders of the NF1 gene [2], and is typically diagnosed using the clinical criteria of the National Institutes of Health, not genetic testing [3].

NF1 is associated with an increased risk of malignancy, including breast cancer. When treating breast cancer, the choice between mastectomy and breast-conserving surgery (BCS) is crucial, and post-BCS radiotherapy (RT) is mandatory [4]. Most breast cancers require multimodal therapy including surgery, radiotherapy, and systemic treatment. Drug selection depends on the breast cancer subtype [5].

One major concern in NF1 patients undergoing BCS is the risk of sarcoma formation after RT [6]. This makes treatment decisions more complex relative to non-NF1 cases. This report discusses the risks of radiotherapy and choice of surgical therapy for an NF1 patient with breast cancer. This paper has been reported in line with the SCARE 2025 Criteria [7].

2. Case report

A 66-year-old woman presented after a right breast mass was detected during screening. Her medical history included NF1, suspected pharyngeal tumor, and cerebral hemorrhage. Her father and eldest son had NF1 but no family history of cancer (Fig. 1).

Fig. 1.

Fig. 1

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Family tree of this patient. The patient is indicated by an arrow.

A clinical examination revealed a tumor in the upper-outer quadrant of the right breast. Mammography showed a 26-mm spiculated mass (Fig. 2). Magnetic resonance imaging confirmed irregular nodular enhancement (Fig. 3). A breast core needle biopsy revealed invasive ductal carcinoma (Fig. 4). CT showed no distant metastasis. NF1-related café-au-lait spots and skin nodules were observed (Fig. 5). Pharyngeal tumors have also been attributed to NF1 [8].

Fig. 2.

Fig. 2

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Right mediolateral oblique view of mammography shows a spiculated mass of the right breast.

Fig. 3.

Fig. 3

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MRI (contrast enhanced T1WI) shows an irregular shaped enhanced mass in the lateral inferior section of the right breast.

A. Sagittal view, B. axial view.

Fig. 4.

Fig. 4

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Postoperative pathological diagnosis was invasive ductal carcinoma of the breast (HE×100).

Fig. 5.

Fig. 5

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Skin nodules and café au lait spots could be seen.

Considering her history, mastectomy was recommended; however, the patient insisted on BCS. A multidisciplinary team was also consulted.

  • •

    Neurosurgeons confirmed no contraindications to surgery.

  • •

    Dermatologists noted a potential risk of hemorrhage due to fibroids at the surgical site.

  • •

    Radiologists stated that post-BCS radiotherapy carried an acceptable risk.

Also we informed the patient about the potential link between NF1 and BRCA1/2 mutations, although her family history suggested a low risk. She planned to discuss this with her family, but we have not received any updates since then.

In April 2023, the patient underwent partial right mastectomy with a sentinel lymph node (SLN) biopsy in a university hospital. A pathological examination confirmed a 22-mm invasive ductal carcinoma (ER, 90 %; PgR, 50 %; HER2-negative; Ki-67, 7 %). One of the two SLNs was positive, but axillary dissection was avoided based on the NCCN Guideline [4]. Postoperatively, the patient received hypofractionated RT (40.5 Gy) for the remaining breast.

Given the risk factors for recurrence and sarcoma formation, chemotherapy was recommended, but she opted for adjuvant endocrine therapy. As of June 2025, there was no recurrence or sarcoma formation over two years of follow-up.

3. Discussion

This report describes a patient with NF1 and breast cancer who opted for BCS and postoperative RT. NF1 is associated with various malignancies, including breast cancer [9], with a five-fold increased incidence in NF1 patients [10].

Challenges in Breast Cancer Diagnosis in NF1:

  • •

    Differentiating breast tumors from underlying skin neurofibromas can be challenging.

  • •

    Mammographic interpretation may be complicated by multiple cutaneous neurofibromas [11].

In this case, the tumor was detected at an early stage (2 cm) and the mammography revealed a spiculated mass.

Risk of Radiation-induced Sarcoma in NF1:

  • A major concern in NF1 patients receiving RT is the risk of sarcoma formation, particularly malignant peripheral nerve sheath tumors (MPNSTs). Studies report:
    • •
      3.5 % of NF1 patients developed neurofibrosarcomas [12].
    • •
      MPNSTs occur in 8–15 % of NF1 patients [13].
    • •
      The median latency from radiotherapy to sarcoma development is 7 years (range, 2–19 years) [14].
  • Some studies argue that the risk is overestimated, stating:
    • •
      The 15-year incidence of radiation-induced sarcoma after breast cancer treatment is only 0.3 % [15].
    • •
      The benefits of adjuvant RT outweigh the risks of secondary malignancies [16].

Clinical Considerations in This Case:

  • 1.

    Radiation Dose: High doses (>120 Gy) increase the sarcoma risk [5,15]. In this case, 40.5 Gy hypofractionated RT was used, which is lower relative to previous studies. Partial breast brachytherapy may further reduce this risk [17].

  • 2.

    Age factor: Younger NF1 patients have a higher risk of radiation-induced malignancies. However, this patient was 66 years old; thus, her relative risk was low [18].

  • 3.

    Comparison with Other Genetic Disorders: Initially, BRCA1/2 mutation carriers were considered sensitive to radiation [19], recent studies have shown that they can safely undergo radiotherapy [20]. Similarly, NF1 patients should not be excluded from RT.

Although this is a retrospective, single case study, it is a rare case of breast cancer with NF1, receiving radiotherapy. There is no recurrence or sarcoma formation after two years and the patient says that “I am satisfied with my conserved breast.”

4. Conclusion

This was a rare case of breast cancer in an NF1 patient who underwent BCS and RT. Although NF1 patients carry the risk of sarcoma formation after RT, no tumor recurrence or sarcoma formation was observed after two years. Based on current evidence, radiation is not absolutely contraindicated in NF1. This case may provide a future option of BCS for patients with breast cancer and NF1. Further population-based studies are needed to clarify the true risk of sarcoma formation in NF1 patients receiving RT.

CRediT authorship contribution statement

  • Kenichiro Tanaka: Conceptualization, Methodology, Data curation, Writing - Original draft preparation.

  • Masami Arai, Shunsuke Sakuraba, Tomoyuki Kushida, Tomoaki Ito, and Goro Kutomi: Writing - Review and editing, Supervision and Project administration.

Consent

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Ethical approval

This study has been given ethical approval.

Guarantor

Kenichiro Tanaka.

Research registration number

This report is registered in the “Research Registry”.

Funding

None.

Declaration of competing interest

No potential conflicts of interest were disclosed.

Acknowledgments

We thank the patient, who agreed to the publication of her images and clinical information.

Informed consent was obtained from the patient for publication of the case.

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