Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/118622
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Type: Journal article
Title: Breast cancer in women with neurofibromatosis type 1 (NF1): a comprehensive case series with molecular insights into its aggressive phenotype
Author: Yap, Y.
Munusamy, P.
Lim, C.
Chan, C.
Prawira, A.
Loke, S.
Lim, S.
Ong, K.
Yong, W.
Ng, S.
Tan, I.
Callen, D.
Lim, J.
Thike, A.
Tan, P.
Lee, A.
Citation: Breast Cancer Research and Treatment, 2018; 171(3):719-735
Publisher: Springer
Issue Date: 2018
ISSN: 0167-6806
1573-7217
Statement of
Responsibility: 
Yoon-Sim Yap, Prabhakaran Munusamy, Cindy Lim, Claire H.T. Chan, Aldo Prawira, Sau-Yeen Loke, Swee-Ho Lim, Kong-Wee Ong, Wei-Sean Yong, Sarah B.H. Ng, Iain B.H. Tan, David F. Callen, Jeffrey C.T. Lim, Aye-Aye Thike, Puay-Hoon Tan, Ann S.G. Lee
Abstract: Purpose: The purpose of the study was to improve the understanding of NF1-associated breast cancer, given the increased risk of breast cancer in this tumour predisposition syndrome and the limited data. Methods: We identified 18 women with NF1 and breast cancer at our institution. Clinical and pathologic characteristics of NF1-associated breast cancers were compared with 7132 breast cancers in patients without NF1 from our institutional database. Next generation sequencing was performed on DNA from blood and breast cancer specimens available. Blood specimens negative for NF1 mutation were subjected to multiplex ligation-dependent probe amplification (MLPA) to identify complete/partial deletions or duplications. Expression of neurofibromin in the NF1-associated breast cancers was evaluated using immunohistochemistry. Results: There was a higher frequency of grade 3 (83.3% vs 45.4%, p = 0.005), oestrogen receptor (ER) negative (66.7% vs 26.3%, p < 0.001) and human epidermal growth factor receptor 2 (HER2)-positive (66.7% vs 23.4%, p < 0.001) tumours among NF1 patients compared to non-NF1 breast cancers. Overall survival was inferior in NF1 patients in multivariable analysis (hazard ratio 2.25, 95% CI 1.11-4.60; p = 0.025). Apart from germline NF1 mutations (11/16; 69%), somatic mutations in TP53 (8/10; 80%), second-hit NF1 (2/10; 20%), KMT2C (4/10; 40%), KMT2D (2/10; 20%), and PIK3CA (2/10; 20%) were observed. Immunohistochemical expression of neurofibromin was seen in the nuclei and/or cytoplasm of all specimens, but without any consistent pattern in the intensity or extent. Conclusions: This comprehensive series of NF1-associated breast cancers suggests that their aggressive features are related to germline NF1 mutations in cooperation with somatic mutations in TP53, KMT2C and other genes.
Keywords: Neurofibromatosis type 1; NF1; tumour suppressor; breast cancer
Rights: © Springer Science+Business Media, LLC, part of Springer Nature 2018
DOI: 10.1007/s10549-018-4851-6
Published version: http://dx.doi.org/10.1007/s10549-018-4851-6
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