Breast cancer and other neoplasms in women with neurofibromatosis type 1: A retrospective review of cases in the Detroit metropolitan area

Wang, Xia; Levin, Albert M.; Smolinski, Sara; Vigneau, Fawn D.; Levin, Nancy K.; Tainsky, Michael A.

doi:10.1002/ajmg.a.35560

Cited by 52 publications

(53 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…That there is an increased risk of developing BC in NF1, and in particular that this risk is greater under the age of 50 years, has now been confirmed in a number of studies, with risks of NF1-BC to age 50 years of 7.8%–8.4%, compared with 2% in the general population 8 10. While studies providing age-corrected standardised incidence ratios (SIR) consistently show an increased risk under age 50 years (95% CI 4.0 to 8.8), the most recent also gives an increased SIR over age 50 years (2.0; 95% CI 1.2 to 3.1), consistent with the non-significant estimate published by Wang et al 11 8 10–14 (table 1). In addition, two studies have reported increased mortality and unfavourable prognostic factors with NF1-BC 8 15.…”

Section: Introductionsupporting

confidence: 82%

Breast cancer risk in neurofibromatosis type 1 is a function of the type of NF1 gene mutation: a new genotype-phenotype correlation

et al. 2018

View full text Add to dashboard Cite

BackgroundNeurofibromatosis type 1 (NF1) predisposes to breast cancer (BC), but no genotype-phenotype correlations have been described.MethodsConstitutional NF1 mutations in 78 patients with NF1 with BC (NF1-BC) were compared with the NF1 Leiden Open Variation Database (n=3432).ResultsNo cases were observed with whole or partial gene deletions (HR 0.10; 95% CI 0.006 to 1.63; p=0.014, Fisher’s exact test). There were no gross relationships with mutation position. Forty-five (64.3%; HR 6.4–83) of the 70 different mutations were more frequent than expected (p<0.05), while 52 (74.3%; HR 5.3–83) were significant when adjusted for multiple comparisons (adjusted p≤0.125; Benjamini-Hochberg). Higher proportions of both nonsense and missense mutations were also observed (adjusted p=0.254; Benjamini-Hochberg). Ten of the 11 missense cases with known age of BC occurred at <50 years (p=0.041). Eighteen cases had BRCA1/2 testing, revealing one BRCA2 mutation.DiscussionThese data strongly support the hypothesis that certain constitutional mutation types, and indeed certain specific variants in NF1 confer different risks of BC. The lack of large deletions and excess of nonsenses and missenses is consistent with gain of function mutations conferring risk of BC, and also that neurofibromin may function as a dimer. The observation that somatic NF1 amplification can occur independently of ERBB2 amplification in sporadic BC supports this concept. A prospective clinical-molecular study of NF1-BC needs to be established to confirm and build on these findings, but regardless of NF1 mutation status patients with NF1-BC warrant testing of other BC-predisposing genes.

show abstract

Section: Introductionsupporting

confidence: 82%

Breast cancer risk in neurofibromatosis type 1 is a function of the type of NF1 gene mutation: a new genotype-phenotype correlation

et al. 2018

View full text Add to dashboard Cite

show abstract

“…There are numerous case reports on NF1 and breast cancer, but less than half a dozen reports containing data that allow generalisation of the results (Sharif et al , 2007; Madanikia et al , 2012; Wang et al , 2012; Seminog and Goldacre, 2015). The data suggest an increased incidence for breast cancer in NF1.…”

mentioning

confidence: 99%

Breast cancer in neurofibromatosis type 1: overrepresentation of unfavourable prognostic factors

et al. 2016

View full text Add to dashboard Cite

Background:An increased breast cancer incidence and poor survival have been reported for women with neurofibromatosis 1 (NF1). To explain the poor survival, we aimed to link the histopathology and clinical characteristics of NF1-associated breast cancers.Methods:The Finnish Cancer Registry and the Finnish NF Registry were cross-referenced to identify the NF1 patients with breast cancer. Archival NF1 breast cancer specimens were retrieved for histopathological typing and compared with matched controls.Results:A total of 32 breast cancers were diagnosed in 1404 NF1 patients during the follow-up. Women with NF1 had an estimated lifetime risk of 18.0% for breast cancer, and this is nearly two-fold compared with that of the general Finnish female population (9.74%). The 26 successfully retrieved archival NF1 breast tumours were more often associated with unfavourable prognostic factors, such as oestrogen and progesterone receptor negativity and HER2 amplification. However, survival was worse in the NF1 group (P=0.053) even when compared with the control group matched for age, diagnosis year, gender and oestrogen receptor status. Scrutiny of The Cancer Genome Atlas data set showed that NF1 mutations and deletions were associated with similar characteristics in the breast cancers of the general population.Conclusions:These results emphasise the role of the NF1 gene in the pathogenesis of breast cancer and a need for active follow-up for breast cancer in women with NF1.

show abstract

“…OPGs, like MPNSTs, may occur in both children and adults [9, 61, 62]. More recently, an increased risk of breast cancer among women with NF1 has also been reported [63, 64]. Breast cancer in NF1 patients appears to have an aggressive phenotype in the two reported case series [65, 66].…”

Section: Introductionmentioning

confidence: 99%

The NF1 gene revisited - from bench to bedside

et al. 2014

View full text Add to dashboard Cite

Neurofibromatosis type 1 (NF1) is a relatively common tumour predisposition syndrome related to germline aberrations of NF1, a tumour suppressor gene. The gene product neurofibromin is a negative regulator of the Ras cellular proliferation pathway, and also exerts tumour suppression via other mechanisms.Recent next-generation sequencing projects have revealed somatic NF1 aberrations in various sporadic tumours. NF1 plays a critical role in a wide range of tumours. NF1 alterations appear to be associated with resistance to therapy and adverse outcomes in several tumour types.Identification of a patient's germline or somatic NF1 aberrations can be challenging, as NF1 is one of the largest human genes, with a myriad of possible mutations. Epigenetic factors may also contribute to inadequate levels of neurofibromin in cancer cells.Clinical trials of NF1-based therapeutic approaches are currently limited. Preclinical studies on neurofibromin-deficient malignancies have mainly been on malignant peripheral nerve sheath tumour cell lines or xenografts derived from NF1 patients. However, the emerging recognition of the role of NF1 in sporadic cancers may lead to the development of NF1-based treatments for other tumour types. Improved understanding of the implications of NF1 aberrations is critical for the development of novel therapeutic strategies.

show abstract

Breast cancer and other neoplasms in women with neurofibromatosis type 1: A retrospective review of cases in the Detroit metropolitan area

Cited by 52 publications

References 12 publications

Breast cancer risk in neurofibromatosis type 1 is a function of the type of NF1 gene mutation: a new genotype-phenotype correlation

Breast cancer risk in neurofibromatosis type 1 is a function of the type of NF1 gene mutation: a new genotype-phenotype correlation

Breast cancer in neurofibromatosis type 1: overrepresentation of unfavourable prognostic factors

The NF1 gene revisited - from bench to bedside

Contact Info

Product

Resources

About