There is a lack of data about the optimal surveillance for individuals with NF1. There is some evidence for genotype-phenotype correlation, however there is currently insufficient data to support variant-specific surveillance protocols.r These management guidelines are based on expert consensus opinion.rrr
In NF1 there is an increased risk of a broad range of cancers/tumours.r Some types of cancer are associated with poorer survival when compared with general population controls, particularly in those diagnosed at age <40 years.rr Concerning symptoms should be investigated promptly.
The type, timing and degree of intervention/surgery, chemotherapy or radiation therapy treatment of NF1 patients (if any) should be made by a multidisciplinary team with experience in managing NF1.rr
Breast cancer (female)
A recent meta-analysis of 4 cohort studies (total of 4178 females) found women with NF1 have a three-fold increased risk of developing breast cancer compared to the general population (SIR = 3.07; 95% CI 2.16-4.38).r Age at diagnosis was available for 181/286, and in this subgroup the mean age at diagnosis was 49.3 years (median 46 years; interquartile range 38.3-58.0 years). Approximately half (53%) were diagnosed age <50 years, with 28% diagnosed between age 35-44 years and 15% age <35 years.
Women with NF1 have poorer breast cancer survival rates compared with women in the general population (estimated 65% vs 90% 5-year survival).rr
Recommendations for breast cancer surveillance are extrapolated from cancer surveillance studies in other groups at increased risk of breast cancer.
As there is increased risk of early breast cancer, surveillance is recommended from age 30 years. Breast MRI is recommended; although there is no data specific to women with NF1, MRI is likely to have higher sensitivity compared with mammography. MRI is also preferred over mammography in young women to reduce ionising radiation exposure.
There is no data regarding the potential benefit of risk-reducing mastectomy in women with NF1. The lifetime risk of breast cancer is in the moderate risk range, therefore risk-reducing mastectomy is not generally recommended.
Malignant peripheral nerve sheath tumour (MPNST)
MPNSTs are aggressive sarcomas that arise in plexiform neurofibroma and are associated with a poor survival. The median age of diagnosis for MPNST is age 30-34 years. Individuals with deep, truncal location of plexiform neurofibroma, previous radiation and an NF1 microdeletion have an increased risk of MPNSTs.
There is no evidence that radiologic surveillance has benefit above early reporting of symptoms. Where available, offer recruitment to research projects to evaluate surveillance protocols using whole body MRI (e.g. SMOC+: see ANZSA Clinical Trials and Studies).
Optic nerve pathway glioma
Most optic nerve gliomas occur between age 3–5 years and do not require intervention.r Optic pathway glioma are rare outside childhood, and lifelong surveillance is not required. Individuals with NF1 are also at risk of other ophthalmological disorders (e.g. retinal vascular abnormalities) and may develop ophthalmological disorders that are common in the general population (e.g. refractive errors, glaucoma, cataract). Recommend review by an optometrist or ophthalmologist as needed based on symptoms, family history and population recommendations.r
Other possible NF1-associated cancers include juvenile myelomonocytic leukaemia, thyroid cancer, malignant fibrous histiocytomas and rhabdomyosarcoma.rr The absolute risks of these cancer/tumour types is small.