Advertisement

Emerging Role of Genomics and Cell-Free DNA in Breast Cancer

  • Lorenzo Gerratana
  • Andrew A. Davis
  • Ami N. Shah
  • Chenyu Lin
  • Carla Corvaja
  • Massimo CristofanilliEmail author
Breast Cancer (EA Comen, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Breast Cancer

Opinion statement

Precision Medicine is gaining momentum as the future gold standard healthcare strategy as it enables treatment optimization and consequently a potential improvement for quality of life and survival. This paradigm shift was possible thanks to new high-throughput genomics technologies, which provide prognostic and predictive information on tumor biology and potential treatment options, as standard pathological procedures are unable to capture both spatial and temporal tumor heterogeneity. As a result of decreasing costs, both solid and liquid-based genomics have an increasingly important role in clinical trials’ screening procedures and are gradually being incorporated into clinical practice. Notwithstanding the great potential, its clinical utility is still a matter of debate and clinicians need to be aware of caveats in interpreting resulting data.

Keywords

Circulating tumor DNA Biomarkers Translational medicine Precision medicine Breast cancer 

Notes

Compliance with Ethical Standards

Conflict of Interest

Lorenzo Gerratana has received investigator-initiated study support from Eisai, has received compensation from Eli Lilly & Co. for participation on an advisory board, and has received reimbursement for travel expenses from Menarini Silicon Biosystems.

Andrew A. Davis has received reimbursement for travel expenses from Menarini Silicon Biosystems.

Ami N. Shah declares that she has no conflict of interest.

Chenyu Lin declares that he has no conflict of interest.

Carla Corvaja declares that she has no conflict of interest.

Massimo Cristofanilli declares that he has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Human Genome Project Completion: Frequently Asked Questions - National Human Genome Research Institute (NHGRI) [Internet]. [cited 2019 Feb 16]. Available from: https://www.genome.gov/11006943/human-genome-project-completion-frequently-asked-questions/
  2. 2.
    The Cost of Sequencing a Human Genome - National Human Genome Research Institute (NHGRI) [Internet]. [cited 2019 Feb 14]. Available from: https://www.genome.gov/sequencingcosts/
  3. 3.
    Nik-Zainal S, Davies H, Staaf J, Ramakrishna M, Glodzik D, Zou X, et al. Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature [internet]. Nat Publ Group; 2016;534:47–54. Available from:  https://doi.org/10.1038/nature17676 CrossRefGoogle Scholar
  4. 4.
    Koboldt DC, Fulton RS, McLellan MD, Schmidt H, Kalicki-Veizer J, McMichael JF, et al. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490:61–70.CrossRefGoogle Scholar
  5. 5.
    Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature [internet]. 2012;490:61–70. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23000897.
  6. 6.
    Stephens PJ, Tarpey PS, Davies H, Van Loo P, Greenman C, Wedge DC, et al. The landscape of cancer genes and mutational processes in breast cancer. Nature [Internet]. 2012;486:400–4. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22722201.
  7. 7.
    Shah SP, Roth A, Goya R, Oloumi A, Ha G, Zhao Y, et al. The clonal and mutational evolution spectrum of primary triple-negative breast cancers. Nature [internet]. 2012;486:395–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22495314.
  8. 8.
    Nik-Zainal S, Davies H, Staaf J, Ramakrishna M, Glodzik D, Zou X, et al. Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature [internet]. 2016;534:47–54. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27135926.
  9. 9.
    Banerji S, Cibulskis K, Rangel-Escareno C, Brown KK, Carter SL, Frederick AM, et al. Sequence analysis of mutations and translocations across breast cancer subtypes. Nature [Internet]. 2012;486:405–9 Available from: http://www.nature.com/articles/nature11154.CrossRefGoogle Scholar
  10. 10.
    Stephens PJ, McBride DJ, Lin M-L, Varela I, Pleasance ED, Simpson JT, et al. Complex landscapes of somatic rearrangement in human breast cancer genomes. Nature [Internet]. 2009;462:1005–10 Available from: http://www.nature.com/articles/nature08645.CrossRefGoogle Scholar
  11. 11.
    Liang X, Vacher S, Boulai A, Bernard V, Baulande S, Bohec M, et al. Targeted next-generation sequencing identifies clinically relevant somatic mutations in a large cohort of inflammatory breast cancer. Breast Cancer Res [Internet]. 2018;20:88. Available from:  https://doi.org/10.1186/s13058-018-1007-x
  12. 12.
    Angus L, Wilting S, Riet J van, Smid M, Steenbruggen T, Tjan-Heijnen V, et al. Abstract GS1–07: the genomic landscape of 501 metastatic breast cancer patients. Cancer Res [Internet]. American Association for Cancer Research; 2019 [cited 2019 Feb 16];79:GS1–07. Available from: http://cancerres.aacrjournals.org/content/79/4_Supplement/GS1-07
  13. 13.
    O’Leary B, Cutts RJ, Liu Y, Hrebien S, Huang X, Fenwick K, et al. The genetic landscape and clonal evolution of breast cancer resistance to palbociclib plus fulvestrant in the PALOMA-3 trial. Cancer Discov [Internet]. 2018;8:1390–403. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30206110.CrossRefGoogle Scholar
  14. 14.••
    Fribbens C, O’Leary B, Kilburn L, Hrebien S, Garcia-Murillas I, Beaney M, et al. Plasma ESR1 mutations and the treatment of estrogen receptor-positive advanced breast Cancer. J Clin Oncol [Internet]. 2016;34:2961–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27269946. Applicability of liquid biopsy for disease monitoring and early resistance detection.
  15. 15.
    Spoerke JM, Gendreau S, Walter K, Qiu J, Wilson TR, Savage H, et al. Heterogeneity and clinical significance of ESR1 mutations in ER-positive metastatic breast cancer patients receiving fulvestrant. Nat Commun [Internet]. 2016;7:11579. Available from: http://www.nature.com/articles/ncomms11579
  16. 16.
    Chandarlapaty S, Chen D, He W, Sung P, Samoila A, You D, et al. Prevalence of ESR1 mutations in cell-free DNA and outcomes in metastatic breast cancer: a secondary analysis of the BOLERO-2 clinical trial. JAMA Oncol [internet]. 2016;2:1310–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27532364.CrossRefGoogle Scholar
  17. 17.
    Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im S-A, Masuda N, et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phas. Lancet Oncol [Internet]. 2016;17:425–39. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26947331.
  18. 18.
    Malone KE, Daling JR, Doody DR, Hsu L, Bernstein L, Coates RJ, et al. Prevalence and predictors of BRCA1 and BRCA2 mutations in a population-based study of breast cancer in white and black American women ages 35 to 64 years. Cancer Res [Internet]. 2006;66:8297–308. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16912212.CrossRefGoogle Scholar
  19. 19.
    Litton JK, Rugo HS, Ettl J, Hurvitz SA, Gonçalves A, Lee K-H, et al. Talazoparib in patients with advanced breast Cancer and a germline BRCA mutation. N Engl J Med [Internet]. 2018;379:753–63. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30110579.CrossRefGoogle Scholar
  20. 20.
    Robson M, Im S-A, Senkus E, Xu B, Domchek SM, Masuda N, et al. Olaparib for metastatic breast Cancer in patients with a germline BRCA mutation. N Engl J Med [Internet]. 2017;377:523–33. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28578601.CrossRefGoogle Scholar
  21. 21.
    Winter C, Nilsson MP, Olsson E, George AM, Chen Y, Kvist A, et al. Targeted sequencing of BRCA1 and BRCA2 across a large unselected breast cancer cohort suggests that one-third of mutations are somatic. Ann Oncol Off J Eur Soc Med Oncol [Internet]. 2016;27:1532–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27194814.CrossRefGoogle Scholar
  22. 22.
    Ross JS, Gay LM, Wang K, Ali SM, Chumsri S, Elvin JA, et al. Nonamplification ERBB2 genomic alterations in 5605 cases of recurrent and metastatic breast cancer: an emerging opportunity for anti-HER2 targeted therapies. Cancer [Internet]. 2016;122:2654–62. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27284958.CrossRefGoogle Scholar
  23. 23.
    Hyman DM, Piha-Paul SA, Won H, Rodon J, Saura C, Shapiro GI, et al. HER kinase inhibition in patients with HER2- and HER3-mutant cancers. Nature [Internet]. 2018;554:189–94. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29420467.
  24. 24.
    Ross J, Chung J, Elvin J, Vergilio J-A, Ramkissoon S, Suh J, et al. Abstract P2–09-15: NTRK fusions in breast cancer: Clinical, pathologic and genomic findings. Cancer Res [Internet]. 2018;78:P2–09-15-P2–09-15. Available from:  https://doi.org/10.1158/1538-7445.SABCS17-P2-09-15
  25. 25.
    Goodman AM, Kato S, Bazhenova L, Patel SP, Frampton GM, Miller V, et al. Tumor mutational burden as an independent predictor of response to immunotherapy in diverse cancers. Mol Cancer Ther [internet]. 2017;16:2598–608. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28835386.CrossRefGoogle Scholar
  26. 26.
    Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SAJR, Behjati S, Biankin A V, et al. Signatures of mutational processes in human cancer. Nature [internet]. 2013;500:415–21. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23945592.
  27. 27.
    Hert DG, Fredlake CP, Barron AE. Advantages and limitations of next-generation sequencing technologies: a comparison of electrophoresis and non-electrophoresis methods. Electrophoresis [Internet] 2008;29:4618–4626. Available from:  https://doi.org/10.1002/elps.200800456 CrossRefGoogle Scholar
  28. 28.
    Hutchison CA. DNA sequencing: bench to bedside and beyond. Nucleic Acids Res [Internet] 2007;35:6227–6237. Available from:  https://doi.org/10.1093/nar/gkm688 CrossRefGoogle Scholar
  29. 29.
    Linnarsson S. Recent advances in DNA sequencing methods – general principles of sample preparation. Exp Cell Res [Internet]. 2010;316:1339–43 Available from: https://linkinghub.elsevier.com/retrieve/pii/S0014482710000984.CrossRefGoogle Scholar
  30. 30.
    Alekseyev YO, Fazeli R, Yang S, Basran R, Maher T, Miller NS, et al. A Next-Generation Sequencing Primer—How Does It Work and What Can It Do? Acad Pathol [Internet]. 2018;5:237428951876652. Available from:  https://doi.org/10.1177/2374289518766521 CrossRefGoogle Scholar
  31. 31.
    Wagle N, Berger MF, Davis MJ, Blumenstiel B, DeFelice M, Pochanard P, Ducar M, van Hummelen P, MacConaill LE, Hahn WC, Meyerson M, Gabriel SB, Garraway LA High-throughput detection of actionable genomic alterations in clinical tumor samples by targeted, Massively Parallel Sequencing Cancer Discov [Internet] 2012;2:82–93. Available from:  https://doi.org/10.1158/2159-8290.CD-11-0184 CrossRefGoogle Scholar
  32. 32.
    Genomic Testing [Internet]. [cited 2019 Feb 13]. Available from: https://www.foundationmedicine.com/genomic-testing
  33. 33.
    Rizzo JM, Buck MJ. Key principles and clinical applications of “next-generation” DNA sequencing. Cancer Prev Res [Internet] 2012;5:887–900. Available from:  https://doi.org/10.1158/1940-6207.CAPR-11-0432 CrossRefGoogle Scholar
  34. 34.
    Rizzo JM, Buck MJ. Key principles and clinical applications of “next-generation” DNA sequencing. Cancer Prev Res. 2012;5:887–900.CrossRefGoogle Scholar
  35. 35.
    Goodwin S, McPherson JD, McCombie WR. Coming of age: ten years of next-generation sequencing technologies. Nat Rev Genet [Internet]. 2016;17:333–51 Available from: http://www.nature.com/articles/nrg.2016.49.CrossRefGoogle Scholar
  36. 36.
    Thompson JF, Steinmann KE. Single Molecule Sequencing with a HeliScope Genetic Analysis System. In: Single molecule sequencing with a HeliScope genetic analysis system. Curr Protoc Mol biol [internet]. Hoboken, NJ: John Wiley & Sons, Inc.; 2010.  https://doi.org/10.1002/0471142727.mb0710s92.CrossRefGoogle Scholar
  37. 37.
    Rhoads A, Au KF. PacBio sequencing and its applications. Genomics Proteomics Bioinformatics [Internet]. 2015;13:278–89 Available from: https://linkinghub.elsevier.com/retrieve/pii/S1672022915001345.CrossRefGoogle Scholar
  38. 38.
    Morganti S, Tarantino P, Ferraro E, D’Amico P, Viale G, Trapani D, et al. Complexity of genome sequencing and reporting: next generation sequencing (NGS) technologies and implementation of precision medicine in real life. Crit Rev Oncol Hematol [Internet]. 2019;133:171–82 Available from: https://linkinghub.elsevier.com/retrieve/pii/S1040842818304220.CrossRefGoogle Scholar
  39. 39.
    Alioto TS, Buchhalter I, Derdak S, Hutter B, Eldridge MD, Hovig E, et al. A comprehensive assessment of somatic mutation detection in cancer using whole-genome sequencing. Nat Commun [Internet]. 2015;6:10001. Available from: http://www.nature.com/articles/ncomms10001
  40. 40.
    Kim K, Seong M-W, Chung W-H, Park SS, Leem S, Park W, et al. Effect of Next-Generation Exome Sequencing Depth for Discovery of Diagnostic Variants. Genomics Inform [Internet]. 2015;13:31. Available from:  https://doi.org/10.5808/GI.2015.13.2.31 CrossRefGoogle Scholar
  41. 41.
    Rusch M, Nakitandwe J, Shurtleff S, Newman S, Zhang Z, Edmonson MN, et al. Clinical cancer genomic profiling by three-platform sequencing of whole genome, whole exome and transcriptome. Nat Commun [Internet]. 2018;9:3962 Available from: http://www.nature.com/articles/s41467-018-06485-7.CrossRefGoogle Scholar
  42. 42.
    Lelieveld SH, Spielmann M, Mundlos S, Veltman JA, Gilissen C. Comparison of exome and genome sequencing Technologies for the Complete Capture of protein-coding regions. Hum Mutat [Internet] 2015;36:815–822. Available from:  https://doi.org/10.1002/humu.22813 CrossRefGoogle Scholar
  43. 43.
    Belkadi A, Bolze A, Itan Y, Cobat A, Vincent QB, Antipenko A, Shang L, Boisson B, Casanova JL, Abel L Whole-genome sequencing is more powerful than whole-exome sequencing for detecting exome variants. Proc Natl Acad Sci [Internet] 2015;112:5473–5478. Available from:  https://doi.org/10.1073/pnas.1418631112 CrossRefGoogle Scholar
  44. 44.
    Horak P, Fröhling S, Glimm H. Integrating next-generation sequencing into clinical oncology: strategies, promises and pitfalls. ESMO Open [Internet]. 2016;1:e000094. Available from:  https://doi.org/10.1136/esmoopen-2016-000094 CrossRefGoogle Scholar
  45. 45.
    Davalos V, Martinez-Cardus A, Esteller M. The epigenomic revolution in breast cancer. Am J Pathol [Internet]. 2017;187:2163–74 Available from: https://linkinghub.elsevier.com/retrieve/pii/S0002944017305825.CrossRefGoogle Scholar
  46. 46.
    Horvath A, Pakala SB, Mudvari P, Reddy SDN, Ohshiro K, Casimiro S, et al. Novel insights into breast cancer genetic variance through RNA sequencing. Sci Rep [Internet]. 2013;3:2256 Available from: http://www.nature.com/articles/srep02256.CrossRefGoogle Scholar
  47. 47.
    Buono G, Gerratana L, Bulfoni M, Provinciali N, Basile D, Giuliano M, et al. Circulating tumor DNA analysis in breast cancer: is it ready for prime-time? Cancer Treat Rev [Internet]. 2019; Available from: https://linkinghub.elsevier.com/retrieve/pii/S0305737219300088 Google Scholar
  48. 48.
    Chae YK, Davis AA, Jain S, Santa-Maria C, Flaum L, Beaubier N, et al. Concordance of genomic alterations by next-generation sequencing in tumor tissue versus circulating tumor DNA in breast cancer. Mol Cancer Ther [Internet]. American Association for Cancer Research; 2017 [cited 2018 Feb 27];16:1412–20. Available from:  https://doi.org/10.1158/1535-7163.MCT-17-0061 CrossRefGoogle Scholar
  49. 49.
    Castro-Giner F, Gkountela S, Donato C, Alborelli I, Quagliata L, Ng C, et al. Cancer diagnosis using a liquid biopsy: challenges and expectations. Diagnostics [Internet]. 2018;8:31 Available from: http://www.mdpi.com/2075-4418/8/2/31.CrossRefGoogle Scholar
  50. 50.
    Zill O, Banks K, Fairclough S, Mortimer S, Vowles J, Mokhtari R, et al. The landscape of actionable genomic alterations in cell-free circulating tumor DNA from 21,807 advanced cancer patients. bioRxiv [Internet]. Cold Spring Harbor Laboratory; 2017 [cited 2018 Feb 28];233205. Available from: https://www.biorxiv.org/content/early/2017/12/12/233205?rss=1&utm_source=dlvr.it&utm_medium=twitter
  51. 51.
    Martínez-Galán J, Torres-Torres B, Núñez MI, López-Peñalver J, Del Moral R, Ruiz De Almodóvar JM, et al. ESR1 gene promoter region methylation in free circulating DNA and its correlation with estrogen receptor protein expression in tumor tissue in breast cancer patients. BMC Cancer [Internet]. 2014;14:59. Available from:  https://doi.org/10.1186/1471-2407-14-59
  52. 52.
    Schiavon G, Hrebien S, Garcia-Murillas I, Cutts RJ, Pearson A, Tarazona N, et al. Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer. Sci Transl Med [Internet]. 2015;7:313ra182. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26560360.
  53. 53.
    Chu D, Paoletti C, Gersch C, VanDenBerg DA, Zabransky DJ, Cochran RL, et al. ESR1 mutations in circulating plasma tumor DNA from metastatic breast cancer patients. Clin Cancer Res [Internet]. 2016;22:993–9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26261103.CrossRefGoogle Scholar
  54. 54.
    Fribbens C, O’Leary B, Kilburn L, Hrebien S, Garcia-Murillas I, Beaney M, et al. Plasma ESR1 Mutations and the treatment of estrogen receptor-positive advanced breast cancer. J Clin Oncol [Internet]. 2016;34:2961–2968. Available from:  https://doi.org/10.1200/JCO.2016.67.3061 CrossRefGoogle Scholar
  55. 55.
    Chandarlapaty S, Chen D, He W, Sung P, Samoila A, You D, Bhatt T, Patel P, Voi M, Gnant M, Hortobagyi G, Baselga J, Moynahan ME Prevalence of ESR1 mutations in cell-free DNA and outcomes in metastatic breast cancer: a secondary analysis of the BOLERO-2 clinical trial. JAMA Oncol [Internet] 2016;2:1310–1315. Available from:  https://doi.org/10.1001/jamaoncol.2016.1279 CrossRefGoogle Scholar
  56. 56.
    Mastoraki S, Strati A, Tzanikou E, Chimonidou M, Politaki E, Voutsina A, et al. ESR1 methylation: a liquid biopsy–based epigenetic assay for the follow-up of patients with metastatic breast cancer receiving endocrine treatment. Clin Cancer Res [Internet]. 2018 [cited 2019 Jan 1];24:1500–10. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29284708.CrossRefGoogle Scholar
  57. 57.••
    André F, Ciruelos EM, Rubovszky G, Campone M, Loibl S, Rugo HS, et al. LBA3_PRAlpelisib (ALP) + fulvestrant (FUL) for advanced breast cancer (ABC): results of the phase III SOLAR-1 trial. Ann Oncol [internet]. 2018;29. Available from:  https://doi.org/10.1093/annonc/mdy424.010/5141523. Use of cancer genomics as predictive assessment for targeted treatment response.
  58. 58.
    Baselga J, Dent SF, Cortés J, Im Y-H, Diéras V, Harbeck N, et al. Phase III study of taselisib (GDC-0032) + fulvestrant (FULV) v FULV in patients (pts) with estrogen receptor (ER)-positive, PIK3CA -mutant (MUT), locally advanced or metastatic breast cancer (MBC): Primary analysis from SANDPIPER. J Clin Oncol [Internet]. 2018;36:LBA1006-LBA1006. Available from:  https://doi.org/10.1200/JCO.2018.36.18_suppl.LBA1006 CrossRefGoogle Scholar
  59. 59.
    O’Leary B, Hrebien S, Morden JP, Beaney M, Fribbens C, Huang X, et al. Early circulating tumor DNA dynamics and clonal selection with palbociclib and fulvestrant for breast cancer. Nat Commun [Internet]. Nature Publishing Group; 2018 [cited 2018 Mar 13];9:896. Available from: http://www.nature.com/articles/s41467-018-03215-x
  60. 60.
    Spoerke JM, Gendreau S, Walter K, Qiu J, Wilson TR, Savage H, et al. Heterogeneity and clinical significance of ESR1 mutations in ER-positive metastatic breast cancer patients receiving fulvestrant. Nat Commun [Internet]. 2016;7:11579. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27174596.
  61. 61.
    Formisano L, Lu Y, Jansen V, Bauer J, Hanker A, Gonzalez Ericsson P, et al. Abstract GS6–05: Gain-of-function kinase library screen identifies FGFR1 amplification as a mechanism of resistance to antiestrogens and CDK4/6 inhibitors in ER+ breast cancer. Cancer Res [Internet]. 2018;78:GS6–05-GS6–05. Available from:  https://doi.org/10.1158/1538-7445.SABCS17-GS6-05
  62. 62.
    Condorelli R, Spring L, O’Shaughnessy J, Lacroix L, Bailleux C, Scott V, et al. Polyclonal RB1 mutations and acquired resistance to CDK 4/6 inhibitors in patients with metastatic breast cancer. Ann Oncol [Internet]. 2018;29:640–5 Available from: https://academic.oup.com/annonc/article/29/3/640/4725051.CrossRefGoogle Scholar
  63. 63.•
    Hartmaier RJ, Trabucco SE, Priedigkeit N, Chung JH, Parachoniak CA, Vanden Borre P, et al. Recurrent hyperactive ESR1 fusion proteins in endocrine therapy resistant breast cancer. Ann Oncol [Internet]. 2018; Available from:  https://doi.org/10.1093/annonc/mdy025/4817340. Proof of concept on the complexity of ESR1-driven treatment resistance.
  64. 64.
    Commissioner O of the. Press Announcements - FDA announces approval, CMS proposes coverage of first breakthrough-designated test to detect extensive number of cancer biomarkers. Office of the Commissioner; [cited 2019 Feb 16]; Available from: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm587273.htm
  65. 65.
    Turnbull C. Introducing whole-genome sequencing into routine cancer care: the genomics England 100 000 genomes project. Ann Oncol [Internet]. 2018;29:784–7 Available from: https://academic.oup.com/annonc/article/29/4/784/4860707.CrossRefGoogle Scholar
  66. 66.
    Lethimonnier F, Levy Y. Genomic medicine France 2025. Ann Oncol [Internet]. 2018;29:783–4 Available from: https://academic.oup.com/annonc/article/29/4/783/4817342.CrossRefGoogle Scholar
  67. 67.
    Drilon A, Laetsch TW, Kummar S, DuBois SG, Lassen UN, Demetri GD, et al. Efficacy of Larotrectinib in TRK fusion–positive cancers in adults and children. N Engl J Med. 2018;378:731–9.CrossRefGoogle Scholar
  68. 68.
    Kim S-B, Dent R, Im S-A, Espié M, Blau S, Tan AR, et al. Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol [Internet]. 2017;18:1360–72 Available from: http://www.ncbi.nlm.nih.gov/pubmed/28800861.CrossRefGoogle Scholar
  69. 69.
    Ma CX, Bose R, Gao F, Freedman RA, Telli ML, Kimmick G, et al. Neratinib efficacy and circulating tumor DNA detection of HER2 mutations in HER2 nonamplified metastatic breast cancer. Clin Cancer Res [Internet]. 2017;23:5687–95. Available from:  https://doi.org/10.1158/1078-0432.CCR-17-0900 CrossRefGoogle Scholar
  70. 70.
    Paolillo C, Mu Z, Rossi G, Schiewer MJ, Nguyen T, Austin L, et al. Detection of activating estrogen receptor gene (ESR1) mutations in single circulating tumor cells. Clin Cancer Res [Internet] 2017;23:6086–6093. Available from:  https://doi.org/10.1158/1078-0432.CCR-17-1173 CrossRefGoogle Scholar
  71. 71.
    Ross JS, Gay LM, Wang K, Ali SM, Chumsri S, Elvin JA, et al. Nonamplification ERBB2 genomic alterations in 5605 cases of recurrent and metastatic breast cancer: An emerging opportunity for anti-HER2 targeted therapies. Cancer [Internet]. 2016;122:2654–62. Available from:  https://doi.org/10.1002/cncr.30102 CrossRefGoogle Scholar
  72. 72.
    Merker JD, Oxnard GR, Compton C, Diehn M, Hurley P, Lazar AJ, et al. Circulating tumor DNA analysis in patients with cancer: American Society of Clinical Oncology and College of American Pathologists Joint Review. J Clin Oncol [Internet]. 2018 [cited 2018 Mar 19];36:JCO.2017.76.867. Available from:  https://doi.org/10.1200/JCO.2017.76.8671 CrossRefGoogle Scholar
  73. 73.
    Pelizzari G, Gerratana L, Basile D, Fanotto V, Bartoletti M, Liguori A, et al. Post-neoadjuvant strategies in breast cancer: From risk assessment to treatment escalation. Cancer Treat Rev [Internet]. Elsevier; 2019 [cited 2018 Nov 1];72:7–14. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0305737218301841 CrossRefGoogle Scholar
  74. 74.
    De Mattos-Arruda L, Weigelt B, Cortes J, Won HH, Ng CKY, Nuciforo P, et al. Capturing intra-tumor genetic heterogeneity by de novo mutation profiling of circulating cell-free tumor DNA: a proof-of-principle. Ann Oncol [Internet] 2014;25:1729–1735. Available from:  https://doi.org/10.1093/annonc/mdu239 CrossRefGoogle Scholar
  75. 75.
    Arneth B. Update on the types and usage of liquid biopsies in the clinical setting: a systematic review. BMC Cancer [Internet]. 2018;18:527. Available from:  https://doi.org/10.1186/s12885-018-4433-3
  76. 76.
    Gold B, Cankovic M, Furtado LV, Meier F, Gocke CD. Do circulating tumor cells, exosomes, and circulating tumor nucleic acids have clinical utility? J Mol Diagnostics [Internet]. 2015;17:209–24 Available from: https://linkinghub.elsevier.com/retrieve/pii/S1525157815000471.CrossRefGoogle Scholar
  77. 77.
    Thakur BK, Zhang H, Becker A, Matei I, Huang Y, Costa-Silva B, et al. Double-stranded DNA in exosomes: a novel biomarker in cancer detection. Cell Res [Internet]. 2014;24:766–9. Available from: http://www.nature.com/articles/cr201444 CrossRefGoogle Scholar
  78. 78.
    Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med [Internet]. 2014;6:224ra24-224ra24. Available from:  https://doi.org/10.1126/scitranslmed.3007094 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Lorenzo Gerratana
    • 1
    • 2
  • Andrew A. Davis
    • 1
  • Ami N. Shah
    • 1
  • Chenyu Lin
    • 1
  • Carla Corvaja
    • 2
  • Massimo Cristofanilli
    • 1
    Email author
  1. 1.Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of MedicineNorthwestern UniversityChicagoUSA
  2. 2.Department of Medicine (DAME) - University of UdineUdine UDItaly

Personalised recommendations