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

Abstract

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.

Breast cancer risk and germline genomic profiling of women with neurofibromatosis type 1 who developed breast cancer

“…The lifetime breast cancer risk estimation of 17.2% is similar to the rate observed in Finland . A French NF1 cohort of n = 565 demonstrated 69.5% with a truncating mutation, 6.5% with an in‐frame splicing mutation, and 7.5% with a missense mutation .…”

“…Pathogenic mutations in NF1 gene only confer a moderate risk of breast cancer. However, these tumors appear to result in worsened survival in comparison to the sporadic counterparts . To define better the targetable individuals who may benefit the most from early screening or prevention, it is logical to search for additional cancer driving factors.…”

Phenotypic and molecular dissection of metaplastic breast cancer and the prognostic implications

“…While the relationship between NF1 alterations and breast cancer is well known , and indeed with aggressive breast cancers , we have presented novel data to support a link between NF1 mutations and the metaplastic subtype, and showed weak heterogeneous expression of NF1 in mutant cases. These data are supported by a series of six recent case reports, each highlighting an ostensibly ‘unique’ case of metaplastic breast cancer in a neurofibromatosis patient (NF1; inherited mutant NF1 syndrome) ; four out of six cases presented with a squamous phenotype, with the remaining two being spindle.…”

Infiltrating Ductal Carcinoma of Breast with Coexistent Neurofibroma-A Rare Association

“…Because breast cancer is a common tumor in the general female population, the exact relationship between neurofibromatosis and breast cancer is still not clear. Uusitalo et al [7] conduct a study on 1404 neurofibromatosis 1 patients and diagnosed breast cancer in 32 patients during follow up. They concluded that women with NF1 had an estimated lifetime risk of 18.0% for breast cancer [7].…”

“…Uusitalo et al [7] conduct a study on 1404 neurofibromatosis 1 patients and diagnosed breast cancer in 32 patients during follow up. They concluded that women with NF1 had an estimated lifetime risk of 18.0% for breast cancer [7]. Da silva et al [8] emphasized the importance of using more intensive clinical and radiological approach like ultrasound and magnetic resonance imaging in early detection of breast cancer in neurofibromatosis 1 patients, as routine mammography is difficult to interpret in these patients due to cutaneous lesions.…”