Frequency of genetic alterations differs in advanced breast cancer between metastatic sites.
breast cancer
metastasis
organotropism
Journal
Genes, chromosomes & cancer
ISSN: 1098-2264
Titre abrégé: Genes Chromosomes Cancer
Pays: United States
ID NLM: 9007329
Informations de publication
Date de publication:
06 Sep 2023
06 Sep 2023
Historique:
revised:
15
08
2023
received:
20
04
2023
accepted:
29
08
2023
medline:
6
9
2023
pubmed:
6
9
2023
entrez:
6
9
2023
Statut:
aheadofprint
Résumé
About 20%-30% of breast cancer (BC) patients will develop distant metastases, preferentially in bones, liver, lung, and brain. BCs with different intrinsic subtypes prefer different sites for metastasis. These subtypes vary in the abundance of genetic alterations which may influence the localization of metastases. Currently, information about the relation between metastatic site and mutational profile of BC is limited. In this study, n = 521 BC metastases of the most frequently affected sites (bone, brain, liver, and lung) were investigated for the frequency of AKT1, ERBB2, ESR1, PIK3CA, and TP53 mutations via NGS and pyrosequencing. Somatic mutations were present in 64% cases. PIK3CA and TP53 were the most frequently mutated genes under study. We provide an analysis of the mutational profile of BCs and the affected metastatic site. Genetic alterations differed significantly depending on the organ site affected by metastases. TP53 mutations were mostly observed in brain metastases (51.0%), metastases outside of the brain revealed a much lower proportion of TP53 mutated samples. PIK3CA mutations are frequent in liver (40.6%), lung (36.8%), and bone metastases (35.7%), whereas less common in brain metastases (18.4%). The highest percentage of ESR1 mutations was observed in liver and lung metastases (about 30% each), whereas metastatic lesions in the brain showed significantly less ESR1 mutations, only in 2.0% of the cases. In summary, we found significant differences of mutational status in mBC depending on the affected organ and intrinsic subtype. Organotropism of metastatic cancer spread may be influenced by the mutational profile of individual BCs.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Deutsche Krebshilfe
Informations de copyright
© 2023 The Authors. Genes, Chromosomes and Cancer published by Wiley Periodicals LLC.
Références
Chen W, Hoffmann AD, Liu H, Liu X. Organotropism: new insights into molecular mechanism of breast cancer metastasis. NPJ Precis Oncol. 2018;2(4):1-12.
Redig AJ, McAllister SS. Breast cancer as a systemic disease: a view of metastasis. J Intern Med. 2013;274(2):113-126.
Ma CX, Reinert T, Chmielewska I, Ellis MJ. Mechanisms of aromatase inhibitor resistance. Nat Rev Cancer. 2015;15(5):261-275.
Schiavon G, Hrebien S, Garcia-Murillas I, et al. Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer. Sci Transl Med. 2015;7(313):313ra182.
Toy W, Shen Y, Won H, et al. ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat Genet. 2013;45(12):1439-1445.
Obenauf AC, Massagué J. Surviving at a distance: organ-specific metastasis. Trends Cancer. 2015;1(1):76-91.
Chiang AC, Massagué J. Molecular basis of metastasis. N Engl J Med. 2008;359(26):2814-2823.
Wan L, Pantel K, Kang Y. Tumor metastasis: moving new biological insights into the clinic. Nat Med. 2013;19(11):1450-1464.
Hess KR, Varadhachary GR, Taylor SH, et al. Metastatic pattern in adenocarcinoma. Cancer. 2006;106(7):1624-1633.
Bryan S, Witzel I, Borgmann K, Oliveira-Ferrer L. Molecular mechanisms associated with brain metastases in HER2-positive and triple negative breast cancers. Cancers. 2021;13(16):4137.
Yates LR, Stian Knappskog S, Wedge D, et al. Genomic evolution of breast cancer metastasis and relapse. Cancer Cell. 2017;32(2):169-184.e7.
Hernandez RK, Wade SW, Reich A, Piroll M, Liede A, Lyman GH. Incidence of bone metastases in patients with solid tumors: analysis of oncology electronic medical records in the United States. BMC Cancer. 2018;18(44):44.
Coleman RE. Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res. 2006;12(20):6243s-6249s.
Harbeck N, Penault-Llorca F, Cortes J, et al. Breast cancer. Nat Rev Dis Primers. 2019;5(1):66.
Perou CM, Sørlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747-752.
Paoletti C, Hayes DF. Molecular testing in breast cancer. Annu Rev Med. 2014;65:95-110.
Arpino G, Generali D, Sapino A, et al. Gene expression profiling in breast cancer: a clinical perspective. Breast. 2013;22(2):109-120.
Reis-Filho JS, Pusztai L. Gene expression profiling in breast cancer: classification, prognostication, and prediction. Lancet. 2011;378(9805):1812-1823.
Gerratana L, Davis AA, Polano M, et al. Understanding the organ tropism of metastatic breast cancer through the combination of liquid biopsy tools. Eur J Cancer. 2021;143:147-157.
Kennecke H, Yerushalmi R, Woods R, et al. Metastatic behavior of breast cancer subtypes. J Clin Oncol. 2010;28(20):3271-3277.
Soni A, Ren Z, Hameed O, et al. Breast cancer subtypes predispose the site of distant metastases. Am J Clin Pathol. 2015;143(4):471-478.
Razavi P, Chang MT, Xu G, et al. The genomic landscape of endocrine-resistant advanced breast cancers. Cancer Cell. 2018;34(3):427-438.e6.
The Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490:61-70.
Largillier R, Ferrero JM, Doyen J, et al. Prognostic factors in 1,038 women with metastatic breast cancer. Ann Oncol. 2008;19(12):2012-2019.
Nguyen DX, Bos PD, Massagué J. Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer. 2009;9(4):274-284.
Fribbens C, O'Leary B, Kilburn L, et al. PlasmaESR1Mutations and the treatment of estrogen receptor-positive advanced breast cancer. J Clin Oncol. 2016;34(25):2961-2968.
Sundaresan TK, Sequist LV, Heymach JV, et al. Detection of T790M, the acquired resistance EGFR mutation, by tumor biopsy versus noninvasive blood-based analyses. Clin Cancer Res. 2016;22(5):1103-1110.
Sokol ES, Feng YX, Jin DX, et al. Loss of function of NF1 is a mechanism of acquired resistance to endocrine therapy in lobular breast cancer. Ann Oncol. 2019;30(1):115-123.
Bertucci F, Ng CKY, Patsouris A, et al. Genomic characterization of metastatic breast cancers. Nature. 2019;569(7757):560-564.
Turner NC, Kingston B, Kilburn LS, et al. Circulating tumour DNA analysis to direct therapy in advanced breast cancer (plasmaMATCH): a multicentre, multicohort, phase 2a, platform trial. Lancet Oncol. 2020;21:1296-1308.
Hyman DM, Piha-Paul SA, Won H, et al. HER kinase inhibition in patients with HER2- and HER3-mutant cancers. Nature. 2018;554(7691):189-194.
Hyman DM, Smyth LM, Donoghue MTA, et al. AKT inhibition in solid tumors with AKT1 mutations. J Clin Oncol. 2017;35(20):2251-2259.
Goncalves MD, Hopkins BD, Cantley LC. Phosphatidylinositol 3-kinase, growth disorders, and cancer. N Engl J Med. 2018;379(21):2052-2062.
André F, Ciruelos E, Gabor RM, et al. Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. N Engl J Med. 2019;380(20):1929-1940.
Duffy MJ, Synnott NC, Crown J. Mutant p53 in breast cancer: potential as a therapeutic target and biomarker. Breast Cancer Res Treat. 2018;170:213-219.
Chae BY, Bae JS, Lee A, et al. p53 as a specific prognostic factor in triple-negative breast cancer. Jpn J Clin Oncol. 2009;39(4):217-224.
Zilfou JT, Lowe SW. Tumor suppressive functions of p53. Cold Spring Harb Perspect Biol. 2009;1(5):a001883.
Huszno J, Grzybowska E. TP53 mutations and SNPs as prognostic and predictive factors in patients with breast cancer. Oncol Lett. 2018;16(1):34-40.
Ellis MJ, Ding L, Shen D, et al. Whole-genome analysis informs breast cancer response to aromatase inhibition. Nature. 2012;486(7403):353-360.
Christgen M, Bartels S, Luft A, et al. Activating human epidermal growth factor receptor 2 (HER2) gene mutation in bone metastases from breast cancer. Virchows Arch. 2018;473(5):577-582.
Bartels S, Christgen M, Luft A, et al. Estrogen receptor (ESR1) mutation in bone metastases from breast cancer. Mod Pathol. 2018;31(1):56-61.
Allison KH, Hammond MEH, Dowsett M, et al. Estrogen and progesterone receptor testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists guideline update. Arch Pathol Lab Med. 2020;144(5):545-563.
Christgen M, Bartels S, Radner M, et al. ERBB2 mutation frequency in lobular breast cancer with pleomorphic histology or high-risk characteristics by molecular expression profiling. Genes Chromosomes Cancer. 2019;58(3):175-185.
Wang K, Li M, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 2010;38(16):e164.
Silwal-Pandit L, Vollan HKM, Chin SF, et al. TP53 mutation spectrum in breast cancer is subtype specific and has distinct prognostic relevance. Clin Cancer Res. 2014;20(13):3569-3580.
Shah SP, Roth A, Goya R, et al. The clonal and mutational evolution spectrum of primary triple-negative breast cancers. Nature. 2012;486(7403):395-399.
Rinaldi J, Sokol ES, Hartmaier RJ, et al. The genomic landscape of metastatic breast cancer: insights from 11,000 tumors. PLoS One. 2020;15(5):e0231999.
Jeselsohn R, De Angelis C, Brown M, Schiff R. The evolving role of the estrogen receptor mutations in endocrine therapy-resistant breast cancer. Curr Oncol Rep. 2017;19(5):35.
Ma CX, Luo J, Naugthon M, et al. A phase I trial of BKM120 (buparlisib) in combination with Fulvestrant in postmenopausal women with estrogen receptor-positive metastatic breast cancer. Clin Cancer Res. 2016;22(7):1583-1591.
Grote I, Bartels S, Kandt L, et al. TP53 mutations are associated with primary endocrine resistance in luminal early breast cancer. Cancer Med. 2021;10(23):8581-8594.
Giltnane JM, Hutchinson KE, Stricker TP, et al. Genomic profiling of ER + breast cancers after short-term estrogen suppression reveals alterations associated with endocrine resistance. Sci Transl Med. 2017;9(402):eaai7993.
Desmedt C, Zoppoli G, Gundem G, et al. Genomic characterization of primary invasive lobular breast cancer. J Clin Oncol. 2016;34(16):1872-1881.
Gellert P, Segal CV, Gao Q, et al. Impact of mutational profiles on response of primary Oestrogen receptor-positive breast cancers to Oestrogen deprivation. Nat Commun. 2016;7:13294.
Li Q, Jiang B, Guo J, et al. INK4 tumor suppressor proteins mediate resistance to CDK4/6 kinase inhibitors. Cancer Discov. 2022;12(2):356-371.
Lefebvre C, Bachelot T, Filleron T, et al. Mutational profile of metastatic breast cancers: a retrospective analysis. PLoS Med. 2016;13(12):e1002201.