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01-10-2018 | Epidemiology

Breast cancer in women with neurofibromatosis type 1 (NF1): a comprehensive case series with molecular insights into its aggressive phenotype

Authors: 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

Published in: Breast Cancer Research and Treatment | Issue 3/2018

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.

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Rasmussen SA, Friedman JM (2000) NF1 gene and neurofibromatosis 1. Am J Epidemiol 151(1):33–40CrossRefPubMed

Griffiths S, Thompson P, Frayling I, Upadhyaya M (2007) Molecular diagnosis of neurofibromatosis type 1: 2 years experience. Fam Cancer 6(1):21–34. https://doi.org/10.1007/s10689-006-9001-3 CrossRefPubMed

Yap YS, McPherson JR, Ong CK, Rozen SG, Teh BT, Lee AS, Callen DF (2014) The NF1 gene revisited—from bench to bedside. Oncotarget 5(15):5873–5892CrossRefPubMedPubMedCentral

Uusitalo E, Rantanen M, Kallionpaa RA, Poyhonen M, Leppavirta J, Yla-Outinen H, Riccardi VM, Pukkala E, Pitkaniemi J, Peltonen S, Peltonen J (2016) Distinctive cancer associations in patients with neurofibromatosis Type 1. J Clin Oncol 34(17):1978–1986. https://doi.org/10.1200/jco.2015.65.3576 CrossRefPubMed

Xu GF, O’Connell P, Viskochil D, Cawthon R, Robertson M, Culver M, Dunn D, Stevens J, Gesteland R, White R (1990) The neurofibromatosis type 1 gene encodes a protein related to GAP. Cell 62(3):599–608CrossRefPubMed

Cawthon RM, Weiss R, Xu GF, Viskochil D, Culver M, Stevens J, Robertson M, Dunn D, Gesteland R, O’Connell P (1990) A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations. Cell 62(1):193–201CrossRefPubMed

Brems H, Beert E, de Ravel T, Legius E (2009) Mechanisms in the pathogenesis of malignant tumours in neurofibromatosis type 1. Lancet Oncol 10(5):508–515. https://doi.org/10.1016/S1470-2045(09)70033-6 CrossRefPubMed

Sharif S, Moran A, Huson SM, Iddenden R, Shenton A, Howard E, Evans DGR (2007) Women with neurofibromatosis 1 are at a moderately increased risk of developing breast cancer and should be considered for early screening. J Med Genet 44(8):481–484. https://doi.org/10.1136/jmg.2007.049346 CrossRefPubMedPubMedCentral

Wang X, Levin AM, Smolinski SE, Vigneau FD, Levin NK, Tainsky MA (2012) Breast cancer and other neoplasms in women with neurofibromatosis type 1: a retrospective review of cases in the Detroit metropolitan area. Am J Med Genet Part A 158A(12):3061–3064. https://doi.org/10.1002/ajmg.a.35560 CrossRefPubMed

10.

Madanikia SA, Bergner A, Ye X, Blakeley JON (2012) Increased risk of breast cancer in women with NF1. Am J Med Genet A 158A(12):3056–3060. https://doi.org/10.1002/ajmg.a.35550 CrossRefPubMedPubMedCentral

11.

Seminog OO, Goldacre MJ (2015) Age-specific risk of breast cancer in women with neurofibromatosis type 1. Br J Cancer 112(9):1546–1548. https://doi.org/10.1038/bjc.2015.78 CrossRefPubMedPubMedCentral

12.

Uusitalo E, Kallionpaa RA, Kurki S, Rantanen M, Pitkaniemi J, Kronqvist P, Harkonen P, Huovinen R, Carpen O, Poyhonen M, Peltonen S, Peltonen J (2017) Breast cancer in neurofibromatosis type 1: overrepresentation of unfavourable prognostic factors. Br J Cancer 116(2):211–217. https://doi.org/10.1038/bjc.2016.403 CrossRefPubMed

13.

Easton DF, Pharoah PD, Antoniou AC, Tischkowitz M, Tavtigian SV, Nathanson KL, Devilee P, Meindl A, Couch FJ, Southey M, Goldgar DE, Evans DG, Chenevix-Trench G, Rahman N, Robson M, Domchek SM, Foulkes WD (2015) Gene-panel sequencing and the prediction of breast-cancer risk. N Engl J Med 372(23):2243–2257. https://doi.org/10.1056/NEJMsr1501341 CrossRefPubMedPubMedCentral

14.

Yap Y-S, Wong J, Chan M, Yong W-S, Ong K-W, Lo S-K, Ngeow J, Tan B, Madhukumar P, Tan M-H, Ang P, Teh B-T, Tan P-H, Lee A-G (2012) Abstract P3-08-09: clinical and pathological characteristics of breast cancer in women with neurofibromatosis Type 1. Cancer Res. https://doi.org/10.1158/0008-5472.sabcs12-p3-08-09 CrossRefPubMedPubMedCentral

15.

Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, Hicks DG, Lester S, Love R, Mangu PB, McShane L, Miller K, Osborne CK, Paik S, Perlmutter J, Rhodes A, Sasano H, Schwartz JN, Sweep FC, Taube S, Torlakovic EE, Valenstein P, Viale G, Visscher D, Wheeler T, Williams RB, Wittliff JL, Wolff AC (2010) American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol 28(16):2784–2795. https://doi.org/10.1200/jco.2009.25.6529 CrossRefPubMedPubMedCentral

16.

Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, Allred DC, Bartlett JM, Bilous M, Fitzgibbons P, Hanna W, Jenkins RB, Mangu PB, Paik S, Perez EA, Press MF, Spears PA, Vance GH, Viale G, Hayes DF (2013) Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol 31(31):3997–4013. https://doi.org/10.1200/jco.2013.50.9984 CrossRefPubMed

17.

Wong ESY, Shekar S, Met-Domestici M, Chan C, Sze M, Yap YS, Rozen SG, Tan M-H, Ang P, Ngeow J, Lee ASG (2016) Inherited breast cancer predisposition in Asians: multigene panel testing outcomes from Singapore. 1:15003. https://doi.org/10.1038/npjgenmed.2015.3. https://www.nature.com/articles/npjgenmed20153#supplementary-information

18.

McPherson JR, Ong CK, Ng CC, Rajasegaran V, Heng HL, Yu WS, Tan BK, Madhukumar P, Teo MC, Ngeow J, Thike AA, Rozen SG, Tan PH, Lee AS, Teh BT, Yap YS (2015) Whole-exome sequencing of breast cancer, malignant peripheral nerve sheath tumor and neurofibroma from a patient with neurofibromatosis type 1. Cancer medicine 4(12):1871–1878. https://doi.org/10.1002/cam4.551 CrossRefPubMedPubMedCentral

19.

Imbard A, Pasmant E, Sabbagh A, Luscan A, Soares M, Goussard P, Blanche H, Laurendeau I, Ferkal S, Vidaud M, Pinson S, Bellanne-Chantelot C, Vidaud D, Wolkenstein P, Parfait B (2015) NF1 single and multi-exons copy number variations in neurofibromatosis type 1. J Hum Genet 60(4):221–224. https://doi.org/10.1038/jhg.2015.6 CrossRefPubMed

20.

McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, Garimella K, Altshuler D, Gabriel S, Daly M, DePristo MA (2010) The genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res 20(9):1297–1303. https://doi.org/10.1101/gr.107524.110 CrossRefPubMedPubMedCentral

21.

Wang K, Li M, Hakonarson H (2010) ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res 38(16):e164. https://doi.org/10.1093/nar/gkq603 CrossRefPubMedPubMedCentral

22.

Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, Marchini JL, McCarthy S, McVean GA, Abecasis GR (2015) A global reference for human genetic variation. Nature 526(7571):68–74. https://doi.org/10.1038/nature15393 CrossRefPubMed

23.

Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, O’Donnell-Luria AH, Ware JS, Hill AJ, Cummings BB, Tukiainen T, Birnbaum DP, Kosmicki JA, Duncan LE, Estrada K, Zhao F, Zou J, Pierce-Hoffman E, Berghout J, Cooper DN, Deflaux N, DePristo M, Do R, Flannick J, Fromer M, Gauthier L, Goldstein J, Gupta N, Howrigan D, Kiezun A, Kurki MI, Moonshine AL, Natarajan P, Orozco L, Peloso GM, Poplin R, Rivas MA, Ruano-Rubio V, Rose SA, Ruderfer DM, Shakir K, Stenson PD, Stevens C, Thomas BP, Tiao G, Tusie-Luna MT, Weisburd B, Won HH, Yu D, Altshuler DM, Ardissino D, Boehnke M, Danesh J, Donnelly S, Elosua R, Florez JC, Gabriel SB, Getz G, Glatt SJ, Hultman CM, Kathiresan S, Laakso M, McCarroll S, McCarthy MI, McGovern D, McPherson R, Neale BM, Palotie A, Purcell SM, Saleheen D, Scharf JM, Sklar P, Sullivan PF, Tuomilehto J, Tsuang MT, Watkins HC, Wilson JG, Daly MJ, MacArthur DG (2016) Analysis of protein-coding genetic variation in 60,706 humans. Nature 536(7616):285–291. https://doi.org/10.1038/nature19057 CrossRefPubMedPubMedCentral

24.

Ng PC, Henikoff S (2003) SIFT: predicting amino acid changes that affect protein function. Nucleic acids research 31(13):3812–3814CrossRefPubMedPubMedCentral

25.

Adzhubei I, Jordan DM, Sunyaev SR (2013) Predicting functional effect of human missense mutations using PolyPhen-2. Curr Protoc Hum Genet. https://doi.org/10.1002/0471142905.hg0720s76 PubMedPubMedCentralCrossRef

26.

Schwarz JM, Cooper DN, Schuelke M, Seelow D (2014) MutationTaster2: mutation prediction for the deep-sequencing age. Nat Methods 11(4):361–362. https://doi.org/10.1038/nmeth.2890 CrossRefPubMed

27.

Reva B, Antipin Y, Sander C (2007) Determinants of protein function revealed by combinatorial entropy optimization. Genome Biol 8(11):R232. https://doi.org/10.1186/gb-2007-8-11-r232 CrossRefPubMedPubMedCentral

28.

Kircher M, Witten DM, Jain P, O’Roak BJ, Cooper GM, Shendure J (2014) A general framework for estimating the relative pathogenicity of human genetic variants. Nat Genet 46(3):310–315. https://doi.org/10.1038/ng.2892 CrossRefPubMedPubMedCentral

29.

Curtis C, Shah SP, Chin S-F, Turashvili G, Rueda OM, Dunning MJ, Speed D, Lynch AG, Samarajiwa S, Yuan Y, Gräf S, Ha G, Haffari G, Bashashati A, Russell R, McKinney S, Langerød A, Green A, Provenzano E, Wishart G, Pinder S, Watson P, Markowetz F, Murphy L, Ellis I, Purushotham A, Børresen-Dale A-L, Brenton JD, Tavaré S, Caldas C, Aparicio S (2012) The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 486(7403):346–352. https://doi.org/10.1038/nature10983 CrossRefPubMedPubMedCentral

30.

Pereira B, Chin SF, Rueda OM, Vollan HK, Provenzano E, Bardwell HA, Pugh M, Jones L, Russell R, Sammut SJ, Tsui DW, Liu B, Dawson SJ, Abraham J, Northen H, Peden JF, Mukherjee A, Turashvili G, Green AR, McKinney S, Oloumi A, Shah S, Rosenfeld N, Murphy L, Bentley DR, Ellis IO, Purushotham A, Pinder SE, Borresen-Dale AL, Earl HM, Pharoah PD, Ross MT, Aparicio S, Caldas C (2016) The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes. Nat Commun 7:11479. https://doi.org/10.1038/ncomms11479 CrossRefPubMedPubMedCentral

31.

Copson ER, Maishman TC, Tapper WJ, Cutress RI, Greville-Heygate S, Altman DG, Eccles B, Gerty S, Durcan LT, Jones L, Evans DG, Thompson AM, Pharoah P, Easton DF, Dunning AM, Hanby A, Lakhani S, Eeles R, Gilbert FJ, Hamed H, Hodgson S, Simmonds P, Stanton L, Eccles DM (2018) Germline BRCA mutation and outcome in young-onset breast cancer (POSH): a prospective cohort study. Lancet Oncol 19(2):169–180. https://doi.org/10.1016/s1470-2045(17)30891-4 CrossRefPubMedPubMedCentral

32.

Mavaddat N, Barrowdale D, Andrulis IL, Domchek SM, Eccles D, Nevanlinna H, Ramus SJ, Spurdle A, Robson M, Sherman M, Mulligan AM, Couch FJ, Engel C, McGuffog L, Healey S, Sinilnikova OM, Southey MC, Terry MB, Goldgar D, O’Malley F, John EM, Janavicius R, Tihomirova L, Hansen TV, Nielsen FC, Osorio A, Stavropoulou A, Benitez J, Manoukian S, Peissel B, Barile M, Volorio S, Pasini B, Dolcetti R, Putignano AL, Ottini L, Radice P, Hamann U, Rashid MU, Hogervorst FB, Kriege M, van der Luijt RB, Peock S, Frost D, Evans DG, Brewer C, Walker L, Rogers MT, Side LE, Houghton C, Weaver J, Godwin AK, Schmutzler RK, Wappenschmidt B, Meindl A, Kast K, Arnold N, Niederacher D, Sutter C, Deissler H, Gadzicki D, Preisler-Adams S, Varon-Mateeva R, Schonbuchner I, Gevensleben H, Stoppa-Lyonnet D, Belotti M, Barjhoux L, Isaacs C, Peshkin BN, Caldes T, de la Hoya M, Canadas C, Heikkinen T, Heikkila P, Aittomaki K, Blanco I, Lazaro C, Brunet J, Agnarsson BA, Arason A, Barkardottir RB, Dumont M, Simard J, Montagna M, Agata S, D’Andrea E, Yan M, Fox S, Rebbeck TR, Rubinstein W, Tung N, Garber JE, Wang X, Fredericksen Z, Pankratz VS, Lindor NM, Szabo C, Offit K, Sakr R, Gaudet MM, Singer CF, Tea MK, Rappaport C, Mai PL, Greene MH, Sokolenko A, Imyanitov E, Toland AE, Senter L, Sweet K, Thomassen M, Gerdes AM, Kruse T, Caligo M, Aretini P, Rantala J, von Wachenfeld A, Henriksson K, Steele L, Neuhausen SL, Nussbaum R, Beattie M, Odunsi K, Sucheston L, Gayther SA, Nathanson K, Gross J, Walsh C, Karlan B, Chenevix-Trench G, Easton DF, Antoniou AC (2012) Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Cancer Epidemiol Biomark Prevent 21 (1):134–147. https://doi.org/10.1158/1055-9965.epi-11-0775 CrossRef

33.

Wilson JR, Bateman AC, Hanson H, An Q, Evans G, Rahman N, Jones JL, Eccles DM (2010) A novel HER2-positive breast cancer phenotype arising from germline TP53 mutations. J Med Genet 47(11):771–774. https://doi.org/10.1136/jmg.2010.078113 CrossRefPubMed

34.

Masciari S, Dillon DA, Rath M, Robson M, Weitzel JN, Balmana J, Gruber SB, Ford JM, Euhus D, Lebensohn A, Telli M, Pochebit SM, Lypas G, Garber JE (2012) Breast cancer phenotype in women with TP53 germline mutations: a Li-Fraumeni syndrome consortium effort. Breast Cancer Res Treat 133(3):1125–1130. https://doi.org/10.1007/s10549-012-1993-9 CrossRefPubMedPubMedCentral

35.

Melhem-Bertrandt A, Bojadzieva J, Ready KJ, Obeid E, Liu DD, Gutierrez-Barrera AM, Litton JK, Olopade OI, Hortobagyi GN, Strong LC, Arun BK (2012) Early onset HER2-positive breast cancer is associated with germline TP53 mutations. Cancer 118(4):908–913. https://doi.org/10.1002/cncr.26377 CrossRefPubMed

36.

Schmidt MK, Tollenaar RA, de Kemp SR, Broeks A, Cornelisse CJ, Smit VT, Peterse JL, van Leeuwen FE, Van’t Veer LJ (2007) Breast cancer survival and tumor characteristics in premenopausal women carrying the CHEK2*1100delC germline mutation. J Clin Oncol 25(1):64–69. https://doi.org/10.1200/jco.2006.06.3024 CrossRefPubMed

37.

Weischer M, Nordestgaard BG, Pharoah P, Bolla MK, Nevanlinna H, Van’t Veer LJ, Garcia-Closas M, Hopper JL, Hall P, Andrulis IL, Devilee P, Fasching PA, Anton-Culver H, Lambrechts D, Hooning M, Cox A, Giles GG, Burwinkel B, Lindblom A, Couch FJ, Mannermaa A, Grenaker Alnaes G, John EM, Dork T, Flyger H, Dunning AM, Wang Q, Muranen TA, van Hien R, Figueroa J, Southey MC, Czene K, Knight JA, Tollenaar RA, Beckmann MW, Ziogas A, Christiaens MR, Collee JM, Reed MW, Severi G, Marme F, Margolin S, Olson JE, Kosma VM, Kristensen VN, Miron A, Bogdanova N, Shah M, Blomqvist C, Broeks A, Sherman M, Phillips KA, Li J, Liu J, Glendon G, Seynaeve C, Ekici AB, Leunen K, Kriege M, Cross SS, Baglietto L, Sohn C, Wang X, Kataja V, Borresen-Dale AL, Meyer A, Easton DF, Schmidt MK, Bojesen SE (2012) CHEK2*1100delC heterozygosity in women with breast cancer associated with early death, breast cancer-specific death, and increased risk of a second breast cancer. J Clin Oncol 30(35):4308–4316. https://doi.org/10.1200/jco.2012.42.7336 CrossRefPubMedPubMedCentral

38.

Schmidt MK, Hogervorst F, van Hien R, Cornelissen S, Broeks A, Adank MA, Meijers H, Waisfisz Q, Hollestelle A, Schutte M, van den Ouweland A, Hooning M, Andrulis IL, Anton-Culver H, Antonenkova NN, Antoniou AC, Arndt V, Bermisheva M, Bogdanova NV, Bolla MK, Brauch H, Brenner H, Bruning T, Burwinkel B, Chang-Claude J, Chenevix-Trench G, Couch FJ, Cox A, Cross SS, Czene K, Dunning AM, Fasching PA, Figueroa J, Fletcher O, Flyger H, Galle E, Garcia-Closas M, Giles GG, Haeberle L, Hall P, Hillemanns P, Hopper JL, Jakubowska A, John EM, Jones M, Khusnutdinova E, Knight JA, Kosma VM, Kristensen V, Lee A, Lindblom A, Lubinski J, Mannermaa A, Margolin S, Meindl A, Milne RL, Muranen TA, Newcomb PA, Offit K, Park-Simon TW, Peto J, Pharoah PD, Robson M, Rudolph A, Sawyer EJ, Schmutzler RK, Seynaeve C, Soens J, Southey MC, Spurdle AB, Surowy H, Swerdlow A, Tollenaar RA, Tomlinson I, Trentham-Dietz A, Vachon C, Wang Q, Whittemore AS, Ziogas A, van der Kolk L, Nevanlinna H, Dork T, Bojesen S, Easton DF (2016) Age- and Tumor Subtype-Specific Breast Cancer Risk Estimates for CHEK2*1100delC Carriers. J Clin Oncol 34 (23):2750–2760. https://doi.org/10.1200/jco.2016.66.5844 CrossRefPubMedPubMedCentral

39.

Heikkinen T, Karkkainen H, Aaltonen K, Milne RL, Heikkila P, Aittomaki K, Blomqvist C, Nevanlinna H (2009) The breast cancer susceptibility mutation PALB2 1592delT is associated with an aggressive tumor phenotype. Clinical Cancer Res 15(9):3214–3222. https://doi.org/10.1158/1078-0432.ccr-08-3128 CrossRef

40.

Antoniou AC, Casadei S, Heikkinen T, Barrowdale D, Pylkas K, Roberts J, Lee A, Subramanian D, De Leeneer K, Fostira F, Tomiak E, Neuhausen SL, Teo ZL, Khan S, Aittomaki K, Moilanen JS, Turnbull C, Seal S, Mannermaa A, Kallioniemi A, Lindeman GJ, Buys SS, Andrulis IL, Radice P, Tondini C, Manoukian S, Toland AE, Miron P, Weitzel JN, Domchek SM, Poppe B, Claes KB, Yannoukakos D, Concannon P, Bernstein JL, James PA, Easton DF, Goldgar DE, Hopper JL, Rahman N, Peterlongo P, Nevanlinna H, King MC, Couch FJ, Southey MC, Winqvist R, Foulkes WD, Tischkowitz M (2014) Breast-cancer risk in families with mutations in PALB2. N Engl J Med 371(6):497–506. https://doi.org/10.1056/NEJMoa1400382 CrossRefPubMedPubMedCentral

41.

Wang X, Teer JK, Tousignant RN, Levin AM, Boulware D, Chitale DA, Shaw BM, Chen Z, Zhang Y, Blakeley JO, Acosta MT, Messiaen LM, Korf BR, Tainsky MA (2018) Breast cancer risk and germline genomic profiling of women with neurofibromatosis type 1 who developed breast cancer. Genes Chromosom Cancer 57(1):19–27. https://doi.org/10.1002/gcc.22503 CrossRefPubMed

42.

Zhu Y, Guignard F, Zhao D, Liu L, Burns DK, Mason RP, Messing A, Parada LF (2005) Early inactivation of p53 tumor suppressor gene cooperating with NF1 loss induces malignant astrocytoma. Cancer Cell 8(2):119–130. https://doi.org/10.1016/j.ccr.2005.07.004 CrossRefPubMedPubMedCentral

43.

Mar VJ, Wong SQ, Li J, Scolyer RA, McLean C, Papenfuss AT, Tothill RW, Kakavand H, Mann GJ, Thompson JF, Behren A, Cebon JS, Wolfe R, Kelly JW, Dobrovic A, McArthur GA (2013) BRAF/NRAS wild-type melanomas have a high mutation load correlating with histologic and molecular signatures of UV damage. Clin Cancer Res 19(17):4589–4598. https://doi.org/10.1158/1078-0432.CCR-13-0398 CrossRefPubMed

44.

Krauthammer M, Kong Y, Ha BH, Evans P, Bacchiocchi A, McCusker JP, Cheng E, Davis MJ, Goh G, Choi M, Ariyan S, Narayan D, Dutton-Regester K, Capatana A, Holman EC, Bosenberg M, Sznol M, Kluger HM, Brash DE, Stern DF, Materin MA, Lo RS, Mane S, Ma S, Kidd KK, Hayward NK, Lifton RP, Schlessinger J, Boggon TJ, Halaban R (2012) Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma. Nat Genet 44(9):1006–1014. https://doi.org/10.1038/ng.2359 CrossRefPubMedPubMedCentral

45.

Sangha N, Wu R, Kuick R, Powers S, Mu D, Fiander D, Yuen K, Katabuchi H, Tashiro H, Fearon ER, Cho KR (2008) Neurofibromin 1 (NF1) defects are common in human ovarian serous carcinomas and co-occur with TP53 mutations. Neoplasia 10(12):1362–1372CrossRefPubMedPubMedCentral

46.

Rao RC, Dou Y (2015) Hijacked in cancer: the KMT2 (MLL) family of methyltransferases. Nat Rev Cancer 15(6):334–346. https://doi.org/10.1038/nrc3929 CrossRefPubMedPubMedCentral

47.

Chen C, Liu Y, Rappaport AR, Kitzing T, Schultz N, Zhao Z, Shroff AS, Dickins RA, Vakoc CR, Bradner JE, Stock W, LeBeau MM, Shannon KM, Kogan S, Zuber J, Lowe SW (2014) MLL3 is a haploinsufficient 7q tumor suppressor in acute myeloid leukemia. Cancer Cell 25(5):652–665. https://doi.org/10.1016/j.ccr.2014.03.016 CrossRefPubMedPubMedCentral

48.

Liu L, Kimball S, Liu H, Holowatyj A, Yang ZQ (2015) Genetic alterations of histone lysine methyltransferases and their significance in breast cancer. Oncotarget 6(4):2466–2482. https://doi.org/10.18632/oncotarget.2967 CrossRefPubMed

49.

Wang XX, Fu L, Li X, Wu X, Zhu Z, Fu L, Dong JT (2011) Somatic mutations of the mixed-lineage leukemia 3 (MLL3) gene in primary breast cancers. Pathol Oncol Res 17(2):429–433. https://doi.org/10.1007/s12253-010-9316-0 CrossRefPubMed

50.

Sato K, Akimoto K (2017) Expression levels of KMT2C and SLC20A1 identified by information-theoretical analysis are powerful prognostic biomarkers in estrogen receptor-positive breast cancer. Clin Breast Cancer 17(3):e135-e142. https://doi.org/10.1016/j.clbc.2016.11.005 CrossRefPubMed

51.

Yates LR, Knappskog S, Wedge D, Farmery JHR, Gonzalez S, Martincorena I, Alexandrov LB, Van Loo P, Haugland HK, Lilleng PK, Gundem G, Gerstung M, Pappaemmanuil E, Gazinska P, Bhosle SG, Jones D, Raine K, Mudie L, Latimer C, Sawyer E, Desmedt C, Sotiriou C, Stratton MR, Sieuwerts AM, Lynch AG, Martens JW, Richardson AL, Tutt A, Lonning PE, Campbell PJ (2017) Genomic evolution of breast cancer metastasis and relapse. Cancer Cell 32(2):169–184.e167. https://doi.org/10.1016/j.ccell.2017.07.005 CrossRefPubMedPubMedCentral

52.

Sabbagh A, Pasmant E, Imbard A, Luscan A, Soares M, Blanché H, Laurendeau I, Ferkal S, Vidaud M, Pinson S, Bellanné-Chantelot C, Vidaud D, Parfait B, Wolkenstein P (2013) NF1 molecular characterization and neurofibromatosis type I genotype-phenotype correlation: the French experience. Hum Mutat 34(11):1510–1518. https://doi.org/10.1002/humu.22392 CrossRefPubMed

53.

Valero MC, Martín Y, Hernández-Imaz E, Marina Hernández A, Meleán G, Valero AM, Javier Rodríguez-Álvarez F, Tellería D, Hernández-Chico C (2011) A highly sensitive genetic protocol to detect NF1 mutations. J Mol Diagn 13(2):113–122. https://doi.org/10.1016/j.jmoldx.2010.09.002 CrossRefPubMed

54.

Maertens O, Johnson B, Hollstein P, Frederick DT, Cooper ZA, Messiaen L, Bronson RT, McMahon M, Granter S, Flaherty K, Wargo JA, Marais R, Cichowski K (2013) Elucidating distinct roles for NF1 in melanomagenesis. Cancer Discov 3(3):338–349. https://doi.org/10.1158/2159-8290.CD-12-0313 CrossRefPubMed

Title: Breast cancer in women with neurofibromatosis type 1 (NF1): a comprehensive case series with molecular insights into its aggressive phenotype
Authors: 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
Publication date: 01-10-2018
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 3/2018
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-018-4851-6

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Keynote webinar | Spotlight on antibody–drug conjugates in cancer

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