Clinical applications of circulating tumor DNA in monitoring breast cancer drug resistance

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

• 1. Bray F, Ferlay J, Soerjomataram I et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 68(6), 394–424 (2018).
  MedlineGoogle Scholar
• 2. Parikh AR, Leshchiner I, Elagina L et al. Liquid versus tissue biopsy for detecting acquired resistance and tumor heterogeneity in gastrointestinal cancers. Nat. Med. 25(9), 1415–1421 (2019).
  Medline CASGoogle Scholar
• 3. Corcoran RB, Chabner BA. Application of cell-free DNA analysis to cancer treatment. N. Engl J. Med. 379(18), 1754–1765 (2018).
  Medline CASGoogle Scholar
• 4. Fernandez-Lazaro D, Garcia Hernandez JL, Garcia AC et al. Liquid biopsy as novel tool in precision medicine: origins, properties, identification and clinical perspective of cancer's biomarkers. Diagnostics (Basel) 10(4), e215 (2020).
  Medline CASGoogle Scholar
• 5. Oliveira KCS, Ramos IB, Silva JMC et al. Current perspectives on circulating tumor DNA, precision medicine, and personalized clinical management of cancer. Mol. Cancer Res. 18(4), 517–528 (2020).
  Medline CASGoogle Scholar
• 6. Mandel P, Metais P. Les acides nucléiques du plasma sanguin chez l'homme. C R Seances Soc. Biol. Fil. 142(3–4), 241–243 (1948). • Describes the presence of cell-free nucleic acid (cfNA) in human blood for the first time.
  Medline CASGoogle Scholar
• 7. Leon SA, Shapiro B, Sklaroff DM et al. Free DNA in the serum of cancer patients and the effect of therapy. Cancer Res. 37(3), 646–650 (1977).
  Medline CASGoogle Scholar
• 8. Wan JCM, Massie C, Garcia-Corbacho J et al. Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nat. Rev. Cancer 17(4), 223–238 (2017).
  Medline CASGoogle Scholar
• 9. Diehl F, Schmidt K, Choti MA et al. Circulating mutant DNA to assess tumor dynamics. Nat. Med. 14(9), 985–990 (2008).
  Medline CASGoogle Scholar
• 10. Stahl T, Bohme MU, Kroger N et al. Digital PCR to assess hematopoietic chimerism after allogeneic stem cell transplantation. Exp. Hematol. 43(6), 462–468 e461 (2015).
  Medline CASGoogle Scholar
• 11. Dressman D, Yan H, Traverso G et al. Transforming single DNA molecules into fluorescent magnetic particles for detection and enumeration of genetic variations. Proc. Natl Acad. Sci. USA 100(15), 8817–8822 (2003).
  Medline CASGoogle Scholar
• 12. Postel M, Roosen A, Laurent-Puig P et al. Droplet-based digital PCR and next generation sequencing for monitoring circulating tumor DNA: a cancer diagnostic perspective. Expert Rev. Mol. Diagn. 18(1), 7–17 (2018).
  Medline CASGoogle Scholar
• 13. Buono G, Gerratana L, Bulfoni M et al. Circulating tumor DNA analysis in breast cancer: is it ready for prime-time? Cancer Treat. Rev. 73, 73–83 (2019).
  Medline CASGoogle Scholar
• 14. Huang T, Zhuge J, Zhang WW. Sensitive detection of BRAF V600E mutation by amplification refractory mutation system (ARMS)–PCR. Biomark. Res. 1(1), 3 (2013).
  MedlineGoogle Scholar
• 15. Forshew T, Murtaza M, Parkinson C et al. Noninvasive identification and monitoring of cancer mutations by targeted deep sequencing of plasma DNA. Sci. Transl. Med. 4(136), 136ra168 (2012).
  Google Scholar
• 16. Kinde I, Wu J, Papadopoulos N et al. Detection and quantification of rare mutations with massively parallel sequencing. Proc. Natl Acad. Sci. U S A 108(23), 9530–9535 (2011).
  MedlineGoogle Scholar
• 17. Newman AM, Bratman SV, To J et al. An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nat. Med. 20(5), 548–554 (2014).
  Medline CASGoogle Scholar
• 18. Weiser DA, West-Szymanski DC, Fraint E et al. Progress toward liquid biopsies in pediatric solid tumors. Cancer Metastasis Rev. 38(4), 553–571 (2019).
  MedlineGoogle Scholar
• 19. Koeppel F, Blanchard S, Jovelet C et al. Whole exome sequencing for determination of tumor mutation load in liquid biopsy from advanced cancer patients. PLoS ONE 12(11), e0188174 (2017).
  MedlineGoogle Scholar
• 20. Nakagawa H, Wardell CP, Furuta M et al. Cancer whole-genome sequencing: present and future. Oncogene 34(49), 5943–5950 (2015).
  Medline CASGoogle Scholar
• 21. Leary RJ, Sausen M, Kinde I et al. Detection of chromosomal alterations in the circulation of cancer patients with whole-genome sequencing. Sci. Transl. Med. 4(162), 162ra154 (2012).
  MedlineGoogle Scholar
• 22. Vendrell JA, Mau-Them FT, Beganton B et al. Circulating cell free tumor DNA detection as a routine tool for lung cancer patient management. Int. J. Mol. Sci. 18(2), 264 (2017).
  Google Scholar
• 23. McBride DJ, Orpana AK, Sotiriou C et al. Use of cancer-specific genomic rearrangements to quantify disease burden in plasma from patients with solid tumors. Genes Chromosomes Cancer 49(11), 1062–1069 (2010).
  Medline CASGoogle Scholar
• 24. Leary RJ, Kinde I, Diehl F et al. Development of personalized tumor biomarkers using massively parallel sequencing. Sci. Transl. Med. 2(20), 20ra14 (2010).
  MedlineGoogle Scholar
• 25. Dawson SJ, Tsui DW, Murtaza M et al. Analysis of circulating tumor DNA to monitor metastatic breast cancer. N. Engl J. Med. 368(13), 1199–1209 (2013).
  Medline CASGoogle Scholar
• 26. Agassi R, Czeiger D, Shaked G et al. Measurement of circulating cell-free DNA levels by a simple fluorescent test in patients with breast cancer. Am. J. Clin. Pathol. 143(1), 18–24 (2015).
  Medline CASGoogle Scholar
• 27. Zhang X, Zhao W, Wei W et al. Parallel analyses of somatic mutations in plasma circulating tumor DNA (ctDNA) and matched tumor tissues in early-stage breast cancer. Clin. Cancer Res. 25(21), 6546–6553 (2019).
  Medline CASGoogle Scholar
• 28. Garcia-Murillas I, Schiavon G, Weigelt B et al. Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. Sci. Transl. Med. 7(302), 302ra133 (2015). •• Highlights the clinical validity and utility of circulating tumor DNA (ctDNA) in detecting minimal residual disease (MRD) in breast cancer via a large-scale, prospective, multicenter study.
  MedlineGoogle Scholar
• 29. Garcia-Murillas I, Chopra N, Comino-Mendez I et al. Assessment of molecular relapse detection in early-stage breast cancer. JAMA Oncol. 5(10), 1473–1478 (2019). •• Highlights the clinical validity and utility of ctDNA in detecting MRD in breast cancer via a large-scale, prospective, multicenter study.
  MedlineGoogle Scholar
• 30. Parsons HA, Rhoades J, Reed SC et al. Sensitive detection of minimal residual disease in patients treated for early-stage breast cancer. Clin. Cancer Res. 26(11), 2556–2564 (2020). •• Highly sensitive detection of MRD, providing an excting preview of future directions in oncology therapy.
  Medline CASGoogle Scholar
• 31. Murtaza M, Dawson SJ, Tsui DW et al. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature 497(7447), 108–112 (2013). •• Utilizing wide coverage exome next-generation sequencing (NGS), detected mutations appearing at the time of treatment showed that cfDNA can be used to characterize the evolutionary genomic map of resistance.
  Medline CASGoogle Scholar
• 32. Emens LA. Breast cancer immunotherapy: facts and hopes. Clin. Cancer Res. 24(3), 511–520 (2018).
  Medline CASGoogle Scholar
• 33. Le DT, Durham JN, Smith KN et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 357(6349), 409–413 (2017).
  Medline CASGoogle Scholar
• 34. Zhao P, Li L, Jiang X et al. Mismatch repair deficiency/microsatellite instability–high as a predictor for anti-PD-1/PD-L1 immunotherapy efficacy. J. Hematol. Oncol. 12(1), 54 (2019).
  MedlineGoogle Scholar
• 35. Chae YK, Davis AA, Agte S et al. Clinical implications of circulating tumor DNA tumor mutational burden (ctDNA TMB) in non-small cell lung cancer. Oncologist 24(6), 820–828 (2019).
  Medline CASGoogle Scholar
• 36. Hellmann MD, Nabet BY, Rizvi H et al. Circulating tumor DNA analysis to assess risk of progression after long-term response to PD-(L)1 blockade in NSCLC. Clin. Cancer Res. 26(12), 2849–2858 (2020).
  Medline CASGoogle Scholar
• 37. Goldberg SB, Narayan A, Kole AJ et al. Early assessment of lung cancer immunotherapy response via circulating tumor DNA. Clin. Cancer Res. 24(8), 1872–1880 (2018).
  Medline CASGoogle Scholar
• 38. Peng W, Chen JQ, Liu C et al. Loss of PTEN promotes resistance to T cell–mediated immunotherapy. Cancer Discov. 6(2), 202–216 (2016).
  Medline CASGoogle Scholar
• 39. George S, Miao D, Demetri GD et al. Loss of PTEN is associated with resistance to anti-PD-1 checkpoint blockade therapy in metastatic uterine leiomyosarcoma. Immunity 46(2), 197–204 (2017).
  Medline CASGoogle Scholar
• 40. 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. 7(313), 313ra182 (2015). •• Verified the evolving role of ESR1 mutations in endocrine therapy–resistant breast cancer using non-invasive liquid biopsies.
  MedlineGoogle Scholar
• 41. Fribbens C, O'Leary B, Kilburn L et al. Plasma ESR1 mutations and the treatment of estrogen receptor–positive advanced breast cancer. J. Clin. Oncol. 34(25), 2961–2968 (2016).
  Medline CASGoogle Scholar
• 42. Chandarlapaty S, Chen D, He W 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. 2(10), 1310–1315 (2016).
  MedlineGoogle Scholar
• 43. Cristofanilli M, DeMichele A, Giorgetti C et al. Predictors of prolonged benefit from palbociclib plus fulvestrant in women with endocrine-resistant hormone receptor–positive/human epidermal growth factor receptor 2–negative metastatic breast cancer in PALOMA-3. Eur. J. Cancer 104, 21–31 (2018).
  Medline CASGoogle Scholar
• 44. Fribbens C, Garcia Murillas I, Beaney M et al. Tracking evolution of aromatase inhibitor resistance with circulating tumour DNA analysis in metastatic breast cancer. Ann. Oncol. 29(1), 145–153 (2018).
  Medline CASGoogle Scholar
• 45. O'Leary B, Cutts RJ, Liu Y et al. The genetic landscape and clonal evolution of breast cancer resistance to palbociclib plus fulvestrant in the PALOMA-3 trial. Cancer Discov. 8(11), 1390–1403 (2018).
  MedlineGoogle Scholar
• 46. Board RE, Wardley AM, Dixon JM et al. Detection of PIK3CA mutations in circulating free DNA in patients with breast cancer. Breast Cancer Res. Treat. 120(2), 461–467 (2010).
  Medline CASGoogle Scholar
• 47. Takeshita T, Yamamoto Y, Yamamoto-Ibusuki M et al. Prognostic role of PIK3CA mutations of cell-free DNA in early-stage triple negative breast cancer. Cancer Sci. 106(11), 1582–1589 (2015). •• Demonstrates the realationship between PIK3CA mutations and PI3K pathway–dependent androgen receptor phosphorylation and its positive prognostic value in triple-negative breast cancer (TNBC).
  Medline CASGoogle Scholar
• 48. O'Leary B, Hrebien S, Morden JP et al. Early circulating tumor DNA dynamics and clonal selection with palbociclib and fulvestrant for breast cancer. Nat. Commun. 9(1), 896 (2018).
  MedlineGoogle Scholar
• 49. Moynahan ME, Chen D, He W et al. Correlation between PIK3CA mutations in cell-free DNA and everolimus efficacy in HR(+), HER2(-) advanced breast cancer: results from BOLERO-2. Br. J. Cancer 116(6), 726–730 (2017).
  Medline CASGoogle Scholar
• 50. Ma F, Zhu W, Guan Y et al. ctDNA dynamics: a novel indicator to track resistance in metastatic breast cancer treated with anti-HER2 therapy. Oncotarget 7(40), 66020–66031 (2016).
  MedlineGoogle Scholar
• 51. Chen Z, Sun T, Yang Z et al. Monitoring treatment efficacy and resistance in breast cancer patients via circulating tumor DNA genomic profiling. Mol. Genet. Genomic Med. 8(2), e1079 (2020).
  Medline CASGoogle Scholar
• 52. Liggett TE, Melnikov AA, Marks JR et al. Methylation patterns in cell-free plasma DNA reflect removal of the primary tumor and drug treatment of breast cancer patients. Int. J. Cancer 128(2), 492–499 (2011).
  Medline CASGoogle Scholar
• 53. Kajabova V, Smolkova B, Zmetakova I et al. RASSF1A promoter methylation levels positively correlate with estrogen receptor expression in breast cancer patients. Transl. Oncol. 6(3), 297–304 (2013).
  MedlineGoogle Scholar
• 54. Mastoraki S, Strati A, Tzanikou E 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. 24(6), 1500–1510 (2018).
  Medline CASGoogle Scholar
• 55. Zmetakova I, Danihel L, Smolkova B et al. Evaluation of protein expression and DNA methylation profiles detected by pyrosequencing in invasive breast cancer. Neoplasma 60(6), 635–646 (2013).
  Medline CASGoogle Scholar
• 56. Muller HM, Widschwendter A, Fiegl H et al. DNA methylation in serum of breast cancer patients: an independent prognostic marker. Cancer Res. 63(22), 7641–7645 (2003).
  MedlineGoogle Scholar
• 57. Martinez-Galan J, Torres-Torres B, Nunez MI 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 14, 59 (2014).
  MedlineGoogle Scholar
• 58. Fiegl H, Millinger S, Mueller-Holzner E et al. Circulating tumor-specific DNA: a marker for monitoring efficacy of adjuvant therapy in cancer patients. Cancer Res. 65(4), 1141–1145 (2005).
  Medline CASGoogle Scholar
• 59. Takahashi H, Kagara N, Tanei T et al. Correlation of methylated circulating tumor DNA with response to neoadjuvant chemotherapy in breast cancer patients. Clin. Breast Cancer 17(1), 61–69.e63 (2017).
  Medline CASGoogle Scholar
• 60. Sharma G, Mirza S, Parshad R et al. DNA methylation of circulating DNA: a marker for monitoring efficacy of neoadjuvant chemotherapy in breast cancer patients. Tumour Biol. (6), 1837–1843 (2012).
  MedlineGoogle Scholar
• 61. Fujita N, Nakayama T, Yamamoto N et al. Methylated DNA and total DNA in serum detected by one-step methylation-specific PCR is predictive of poor prognosis for breast cancer patients. Oncology 83(5), 273–282 (2012).
  Medline CASGoogle Scholar
• 62. Li Z, Guo X, Tang L et al. Methylation analysis of plasma cell-free DNA for breast cancer early detection using bisulfite next-generation sequencing. Tumour Biol. 37(10), 13111–13119 (2016).
  Medline CASGoogle Scholar
• 63. Panagopoulou M, Karaglani M, Balgkouranidou I et al. Circulating cell-free DNA in breast cancer: size profiling, levels, and methylation patterns lead to prognostic and predictive classifiers. Oncogene 38(18), 3387–3401 (2019). •• Comprehensively explored the role of ctDNA levels and methylated DNA in the prognosis of breast cancer.
  Medline CASGoogle Scholar
• 64. van Steenhoven JEC, Kuijer A, van Diest PJ et al. Conventional pathology versus gene signatures for assessing luminal A and B type breast cancers: results of a prospective cohort study. Genes (Basel) 9(5), 261 (2018).
  Google Scholar
• 65. Robinson DR, Wu YM, Vats P et al. Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat. Genet. 45(12), 1446–1451 (2013).
  Medline CASGoogle Scholar
• 66. Jeselsohn R, Buchwalter G, De Angelis C et al. ESR1 mutations – a mechanism for acquired endocrine resistance in breast cancer. Nat. Rev. Clin. Oncol. 12(10), 573–583 (2015).
  Medline CASGoogle Scholar
• 67. Samuels Y, Velculescu VE. Oncogenic mutations of PIK3CA in human cancers. Cell Cycle 3(10), 1221–1224 (2004).
  Medline CASGoogle Scholar
• 68. Ellis MJ, Lin L, Crowder R et al. Phosphatidyl-inositol-3-kinase alpha catalytic subunit mutation and response to neoadjuvant endocrine therapy for estrogen receptor positive breast cancer. Breast Cancer Res. Treat. 119(2), 379–390 (2010).
  Medline CASGoogle Scholar
• 69. Wang DS, Liu ZX, Lu YX et al. Liquid biopsies to track trastuzumab resistance in metastatic HER2-positive gastric cancer. Gut 68(7), 1152–1161 (2019).
  Medline CASGoogle Scholar
• 70. Ramirez-Ardila DE, Helmijr JC, Look MP et al. Hotspot mutations in PIK3CA associate with first-line treatment outcome for aromatase inhibitors but not for tamoxifen. Breast Cancer Res. Treat. 139(1), 39–49 (2013).
  Medline CASGoogle Scholar
• 71. Baselga J, Im SA, Iwata H et al. Buparlisib plus fulvestrant versus placebo plus fulvestrant in postmenopausal, hormone receptor–positive, HER2-negative, advanced breast cancer (BELLE-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 18(7), 904–916 (2017).
  Medline CASGoogle Scholar
• 72. Di Leo A, Johnston S, Lee KS et al. Buparlisib plus fulvestrant in postmenopausal women with hormone-receptor-positive, HER2-negative, advanced breast cancer progressing on or after mTOR inhibition (BELLE-3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 19(1), 87–100 (2018).
  MedlineGoogle Scholar
• 73. Andre F, Ciruelos E, Rubovszky G et al. Alpelisib for PIK3CA-mutated, hormone receptor–positive advanced breast cancer. N. Engl J. Med. 380(20), 1929–1940 (2019). •• Clinical trial focused on the role of plasma PIK3CA mutations in breast cancer and promoted the first PI3K inhibitor for breast cancer approved by US FDA.
  Medline CASGoogle Scholar
• 74. Markham A. Alpelisib: first global approval. Drugs 79(11), 1249–1253 (2019).
  Medline CASGoogle Scholar
• 75. Curtis C, Shah SP, Chin SF et al. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 486(7403), 346–352 (2012).
  Medline CASGoogle Scholar
• 76. Ciriello G, Miller ML, Aksoy BA et al. Emerging landscape of oncogenic signatures across human cancers. Nat. Genet. 45(10), 1127–1133 (2013).
  Medline CASGoogle Scholar
• 77. Yang X, Zhang K, Zhang C et al. Accuracy of analysis of cfDNA for detection of single nucleotide variants and copy number variants in breast cancer. BMC Cancer 19(1), 465 (2019).
  MedlineGoogle Scholar
• 78. Nebbioso A, Tambaro FP, Dell'Aversana C et al. Cancer epigenetics: moving forward. PLoS Genet. 14(6), e1007362 (2018).
  MedlineGoogle Scholar
• 79. Kang G, Chen K, Yang F et al. Monitoring of circulating tumor DNA and its aberrant methylation in the surveillance of surgical lung cancer patients: protocol for a prospective observational study. BMC Cancer 19(1), 579 (2019).
  MedlineGoogle Scholar
• 80. Li Z, Guo X, Wu Y et al. Methylation profiling of 48 candidate genes in tumor and matched normal tissues from breast cancer patients. Breast Cancer Res. Treat. 149(3), 767–779 (2015).
  Medline CASGoogle Scholar
• 81. Alix-Panabieres C, Pantel K. Clinical applications of circulating tumor cells and circulating tumor DNA as liquid biopsy. Cancer Discov. 6(5), 479–491 (2016). •• Compact review of circulating tumor cell (CTC) and ctDNA application in cancer management
  Medline CASGoogle Scholar
• 82. Li J, Han X, Yu X et al. Clinical applications of liquid biopsy as prognostic and predictive biomarkers in hepatocellular carcinoma: circulating tumor cells and circulating tumor DNA. J. Exp. Clin. Cancer Res. 37(1), 213 (2018).
  MedlineGoogle Scholar
• 83. Cristofanilli M, Budd GT, Ellis MJ et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N. Engl J. Med. 351(8), 781–791 (2004). •• First study regarding the cutoff number of CTCs in human breast cancer.
  Medline CASGoogle Scholar
• 84. Deutsch TM, Riethdorf S, Fremd C et al. HER2-targeted therapy influences CTC status in metastatic breast cancer. Breast Cancer Res. Treat.182(1), 127–136 (2020).
  Google Scholar
• 85. Deutsch TM, Stefanovic S, Feisst M et al. Cut-off analysis of CTC change under systemic therapy for defining early therapy response in metastatic breast cancer. Cancers 12(4), 1055 (2020).
  CASGoogle Scholar
• 86. Lv Q, Gong L, Zhang T et al. Prognostic value of circulating tumor cells in metastatic breast cancer: a systemic review and meta-analysis. Clin. Transl. Oncol. 18(3), 322–330 (2016).
  Medline CASGoogle Scholar
• 87. D'Oronzo S, Lovero D, Palmirotta R et al. Dissection of major cancer gene variants in subsets of circulating tumor cells in advanced breast cancer. Sci. Rep. 9(1), 17276 (2019).
  MedlineGoogle Scholar
• 88. Wang C, Mu Z, Ye Z et al. Prognostic value of HER2 status on circulating tumor cells in advanced-stage breast cancer patients with HER2-negative tumors. Breast Cancer Res. Treat. 181(3), 679–689 (2020).
  Medline CASGoogle Scholar
• 89. Beije N, Sieuwerts AM, Kraan J et al. Estrogen receptor mutations and splice variants determined in liquid biopsies from metastatic breast cancer patients. Mol. Oncol. 12(1), 48–57 (2018).
  Medline CASGoogle Scholar
• 90. Li H, Liu J, Chen J et al. A serum microRNA signature predicts trastuzumab benefit in HER2-positive metastatic breast cancer patients. Nat. Commun. 9(1), 1614 (2018).
  MedlineGoogle Scholar
• 91. Mazel M, Jacot W, Pantel K et al. Frequent expression of PD-L1 on circulating breast cancer cells. Mol. Oncol. 9(9), 1773–1782 (2015).
  Medline CASGoogle Scholar
• 92. Papadaki MA, Koutsopoulos AV, Tsoulfas PG et al. Clinical relevance of immune checkpoints on circulating tumor cells in breast cancer. Cancers (Basel) 12(2), 376 (2020).
  CASGoogle Scholar
• 93. Hrebien S, Citi V, Garcia-Murillas I et al. Early ctDNA dynamics as a surrogate for progression-free survival in advanced breast cancer in the BEECH trial. Ann. Oncol. 30(6), 945–952 (2019).
  Medline CASGoogle Scholar
• 94. Rothwell DG, Ayub M, Cook N et al. Utility of ctDNA to support patient selection for early phase clinical trials: the TARGET study. Nat. Med. 25(5), 738–743 (2019). •• Big step for ctDNA in guiding therapy selection in early-phase clinical trials.
  Medline CASGoogle Scholar
• 95. Clinical trials. Available from: https://clinicaltrials.gov/
  Google Scholar
• 96. Grolz D, Hauch S, Schlumpberger M et al. Liquid biopsy preservation solutions for standardized pre-analytical workflows—venous whole blood and plasma. Curr. Pathobiol. Rep. 6(4), 275–286 (2018).
  MedlineGoogle Scholar
• 97. Ghini V, Quaglio D, Luchinat C et al. NMR for sample quality assessment in metabolomics. N. Biotechnol. 52, 25–34 (2019).
  Medline CASGoogle Scholar
• 98. Condorelli R, Spring L, O'Shaughnessy J et al. Polyclonal RB1 mutations and acquired resistance to CDK 4/6 inhibitors in patients with metastatic breast cancer. Ann. Oncol. 29(3), 640–645 (2018).
  Medline CASGoogle Scholar
• 99. Formisano L, Lu Y, Servetto A et al. Aberrant FGFR signaling mediates resistance to CDK4/6 inhibitors in ER+ breast cancer. Nat. Commun. 10(1), 1373 (2019).
  MedlineGoogle Scholar