Is there a relationship between estrogen and malignant peripheral nerve sheath tumors (neurofibrosarcoma)?

From the Guidelines

There is no established direct relationship between estrogen and neurofibrosarcoma, and hormonal changes are not considered a primary driver in the development or progression of neurofibrosarcomas. Neurofibrosarcomas (also called malignant peripheral nerve sheath tumors) are rare soft tissue sarcomas that can develop in patients with neurofibromatosis type 1 (NF1) [ 1 ]. Some research indicates that hormonal changes (such as those occurring during pregnancy or puberty) have been observed to sometimes accelerate the growth of neurofibromas, which can potentially transform into neurofibrosarcomas. However, a study found that expression of progesterone receptors has been found in 75% of neurofibromas, and a survey of 59 women with NF1 found that 53 (89%) who received oral estrogen-progestogen or pure progestogen preparations reported no associated neurofibroma growth [ 1 ].

Key Points

• The main pathogenic mechanism involves mutations in the NF1 gene and other genetic alterations [ 1 ].
• Currently, there are no established hormone-based treatments for neurofibrosarcomas, and standard therapy typically involves surgical resection, often combined with radiation therapy and sometimes chemotherapy.
• Patients with neurofibrosarcoma should be managed by multidisciplinary teams with expertise in sarcoma treatment rather than focusing on hormonal interventions.
• A retrospective, population-based cohort study in the USA found that NF1 was associated with a statistically significant excess of maternal morbidity, but not maternal mortality [ 1 ].

Considerations

• The benefits of oral or depot contraceptives in women with NF1 likely outweigh any theoretical concerns [ 1 ].
• If oral or depot contraceptives are required to treat a medical condition, the benefits are likely greater than any theoretical concerns [ 1 ].

From the Research

Relationship Between Estrogen and Neurofibrosarcoma

• There is evidence to suggest a relationship between estrogen and neurofibrosarcoma, particularly in the context of neurofibromatosis type 1 (NF1) 2.
• NF1 is a genetic disorder that increases the risk of developing various types of tumors, including neurofibrosarcoma, which is a type of malignant peripheral nerve sheath tumor (MPNST) 3, 4, 5, 6.
• A study found that NF1 deficiency correlates with estrogen receptor signaling and diminished survival in breast cancer, suggesting a potential link between estrogen and NF1-related tumors 2.
• The study used CRISPR-Cas9 gene editing to create Nf1 rat models and found that Nf1 deficiency induced highly penetrant, aggressive mammary adenocarcinomas that express estrogen receptor (ER) and progesterone receptor (PR) 2.
• Additionally, the study found that NF1-deficient cancers correlated with established RAS activation signatures and that estrogen-dependence was verified by estrogen-ablation in Nf1 rats, where rapid tumor regression was observed 2.

Estrogen Receptor Signaling and NF1

• The study suggests that NF1 deficiency may be linked to estrogen receptor signaling, which could play a role in the development and progression of NF1-related tumors, including neurofibrosarcoma 2.
• The identification of distinct Nf1 mRNA and protein isoforms that were altered during tumorigenesis may provide insight into the molecular mechanisms underlying NF1-related tumors 2.
• The correlation between NF1 deficiency and estrogen receptor signaling highlights a potential functional link between neurofibromin and the estrogen receptor, which could have implications for the development of targeted therapies for NF1-related tumors 2.