Cancer incidence and the risk for multiple primary cancers in neurofibromatosis type 1.

Pathogenic variants in the NF1 gene predispose to a broad tumour spectrum, including a moderate-level breast cancer risk in women.

Neurofibromatosis type 1 is a cancer predisposition syndrome caused by pathogenic variants in the NF1 gene, but the risk of multiple primary cancers remains poorly quantified. The Finnish NF1 cohort was extended to 1,811 individuals with verified NF1 and followed through linkage with the nationwide Finnish Cancer Registry over 30,612 person-years between 1987 and 2020. A total of 296 first primary cancers were observed, yielding a standardised incidence ratio (SIR) of 4.92 (95% CI 4.38-5.52), and 59 second primary cancers, SIR 4.30 (95% CI 3.27-5.54): a history of first primary cancer therefore did not, in general, alter the risk of a second primary cancer (p = 0.377). Cumulative cancer risk increased steadily throughout life and affected women had a 20.9% lifetime risk of breast cancer (95% CI 15.9-27.4%), with significantly increased incidence both before 50 years (SIR 4.90; 95% CI 2.99-7.56) and at 50 years or above (SIR 2.67; 95% CI 1.76-3.89).

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The finding that transfers directly to the clinic is the persistence of excess breast cancer risk beyond 50: it undermines the still common practice of stopping dedicated breast surveillance at that age in NF1 patients. The reassuring message about second cancers needs qualifying, since the authors themselves acknowledge that some subpopulations probably concentrate the risk of multiple cancers without the cohort being able to identify them. These are registry data: they provide incidence rates, not genotypes, hence no stratification by NF1 variant type or by benign tumour burden.

Analysis by Dr Thibaut Benquey