Abstract
Background
The recent advancement in massively parallel sequencing technologies has empowered liquid biopsies, in particular circulating tumor DNA (ctDNA) analysis, to be the new paradigm in personalized cancer management. Plasma ctDNA detection overcomes the current limitations in tumor tissue procurement and serves as a convenient and non-invasive method to capture tumor heterogeneity and genetic evolution along patients' cancer journey.
Summary of findings
In breast cancer, the current clinical application of ctDNA includes real-time monitoring of tumor response, detection of drug-resistant clones, assessing dynamic variations in tumor mutational landscape, identifying actionable mutations, detecting minimal residual disease and screening of early tumor.
Purpose
This review aims to summarize the current clinical evidence of ctDNA application in the management of breast cancer.
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References
Abraham J, Montero AJ, Jankowitz RC et al (2019) Safety and efficacy of T-DM1 plus neratinib in patients with metastatic HER2-positive breast cancer: NSABP Foundation Trial FB-10. JCO 37:2601–2609. https://doi.org/10.1200/JCO.19.00858
Allouchery V, Beaussire L, Perdrix A et al (2018) Circulating ESR1 mutations at the end of aromatase inhibitor adjuvant treatment and after relapse in breast cancer patients. Breast Cancer Res 20:40. https://doi.org/10.1186/s13058-018-0968-0
André F, Hurvitz S, Fasolo A et al (2016) Molecular alterations and everolimus efficacy in human epidermal growth factor receptor 2-overexpressing metastatic breast cancers: combined exploratory biomarker analysis from BOLERO-1 and BOLERO-3. JCO 34:2115–2124. https://doi.org/10.1200/JCO.2015.63.9161
André F, Ciruelos E, Rubovszky G et al (2019) Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. N Engl J Med 380:1929–1940. https://doi.org/10.1056/NEJMoa1813904
Angus L, Smid M, Wilting SM et al (2019) The genomic landscape of metastatic breast cancer highlights changes in mutation and signature frequencies. Nat Genet 51:1450–1458. https://doi.org/10.1038/s41588-019-0507-7
Ashworth A (2008) A synthetic lethal therapeutic approach: poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair. JCO 26:3785–3790. https://doi.org/10.1200/JCO.2008.16.0812
Auton A, Abecasis GR, Altshuler DM et al (2015) A global reference for human genetic variation. Nature 526:68–74. https://doi.org/10.1038/nature15393
Bardia A, Hurvitz SA, DeMichele A et al (2019) Triplet therapy (continuous ribociclib, everolimus, exemestane) in HR+/HER2− advanced breast cancer postprogression on a CDK4/6 inhibitor (TRINITI-1): efficacy, safety, and biomarker results. JCO 37:1016–1016. https://doi.org/10.1200/JCO.2019.37.15_suppl.1016
Baselga J, Campone M, Piccart M et al (2012) Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med 366:520–529. https://doi.org/10.1056/NEJMoa1109653
Baselga J, Cortés J, Im S-A et al (2014) Biomarker analyses in CLEOPATRA: a phase iii, placebo-controlled study of pertuzumab in human epidermal growth factor receptor 2-positive, first-line metastatic breast cancer. JCO 32:3753–3761. https://doi.org/10.1200/JCO.2013.54.5384
Baselga J, Im S-A, Iwata H et al (2017) 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 18:904–916. https://doi.org/10.1016/S1470-2045(17)30376-5
Baselga J, Sellami D, El-Hashimy M et al (2018) Abstract A050: PIK3CA mutation status in tumor tissue and ctDNA as a biomarker for PFS in patients with HR+, HER2- ABC treated with buparlisib or placebo plus fulvestrant: results from the BELLE-2 and BELLE-3 randomized studies. Mol Cancer Ther 17:A050. https://doi.org/10.1158/1535-7163.TARG-17-A050
Berns K, Horlings HM, Hennessy BT et al (2007) A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell 12:395–402. https://doi.org/10.1016/j.ccr.2007.08.030
Bertucci F, Ng CKY, Patsouris A et al (2019) Genomic characterization of metastatic breast cancers. Nature 569:560–564. https://doi.org/10.1038/s41586-019-1056-z
Bettegowda C, Sausen M, Leary RJ et al (2014) Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med 6:224ra24. https://doi.org/10.1126/scitranslmed.3007094
Bidard F-C, Callens C, Pistilli B et al (2019) Emergence of ESR1 mutation in cell-free DNA during first line aromatase inhibitor and palbociclib: an exploratory analysis of the PADA-1 trial. Ann Oncol 30:v105–v106. https://doi.org/10.1093/annonc/mdz242.002
Bidard FC, Callens C, Dalenc F et al (2020) Prognostic impact of ESR1 mutations in ER+ HER2− MBC patients prior treated with first line AI and palbociclib: an exploratory analysis of the PADA-1 trial. JCO 38:1010. https://doi.org/10.1200/JCO.2020.38.15_suppl.1010
Butler TM, Johnson-Camacho K, Peto M et al (2015) Exome sequencing of cell-free DNA from metastatic cancer patients identifies clinically actionable mutations distinct from primary disease. PLoS ONE 10:e0136407. https://doi.org/10.1371/journal.pone.0136407
Cavallone L, Aguilar-Mahecha A, Lafleur J et al (2020) Prognostic and predictive value of circulating tumor DNA during neoadjuvant chemotherapy for triple negative breast cancer. Sci Rep 10:14704. https://doi.org/10.1038/s41598-020-71236-y
Chandarlapaty S, Chen D, He W et al (2016) 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 2:1310–1315. https://doi.org/10.1001/jamaoncol.2016.1279
Chia S, Gradishar W, Mauriac L et al (2008) Double-blind, randomized placebo controlled trial of fulvestrant compared with exemestane after prior nonsteroidal aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive, advanced breast cancer: results from EFECT. JCO 26:1664–1670. https://doi.org/10.1200/JCO.2007.13.5822
Chmura SJ, Winter KA, Al-Hallaq HA et al (2019) NRG-BR002: a phase IIR/III trial of standard of care therapy with or without stereotactic body radiotherapy (SBRT) and/or surgical ablation for newly oligometastatic breast cancer (NCT02364557). JCO 37:TPS1117. https://doi.org/10.1200/JCO.2019.37.15_suppl.TPS1117
Clark TA, Chung JH, Kennedy M et al (2018) Analytical validation of a hybrid capture-based next-generation sequencing clinical assay for genomic profiling of cell-free circulating tumor DNA. J Mol Diagn 20:686–702. https://doi.org/10.1016/j.jmoldx.2018.05.004
Cohen JD, Li L, Wang Y et al (2018) Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science 359:926–930. https://doi.org/10.1126/science.aar3247
Condorelli R, Spring L, O’Shaughnessy J et al (2018) Polyclonal RB1 mutations and acquired resistance to CDK 4/6 inhibitors in patients with metastatic breast cancer. Ann Oncol 29:640–645. https://doi.org/10.1093/annonc/mdx784
Cooke T, Reeves J, Lanigan A, Stanton P (2001) HER2 as a prognostic and predictive marker for breast cancer. Ann Oncol 12(Suppl 1):S23-28. https://doi.org/10.1093/annonc/12.suppl_1.s23
Coombes RC, Page K, Salari R et al (2019) Personalized detection of circulating tumor DNA antedates breast cancer metastatic recurrence. Clin Cancer Res 25:4255. https://doi.org/10.1158/1078-0432.CCR-18-3663
Cristofanilli M, Turner NC, Bondarenko I et al (2016) 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, phase 3 randomised controlled trial. Lancet Oncol 17:425–439. https://doi.org/10.1016/S1470-2045(15)00613-0
Dawson S-J, Tsui DWY, Murtaza M et al (2013) Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med 368:1199–1209. https://doi.org/10.1056/NEJMoa1213261
Dickler M, Bardia A, Mayer I et al (2015) Abstract CT231: a first-in-human phase I study to evaluate the oral selective estrogen receptor degrader GDC-0810 (ARN-810) in postmenopausal women with estrogen receptor+ HER2−, advanced/metastatic breast cancer. Cancer Res 75:CT231. https://doi.org/10.1158/1538-7445.AM2015-CT231
Diehl F, Schmidt K, Choti MA et al (2008) Circulating mutant DNA to assess tumor dynamics. Nat Med 14:985–990. https://doi.org/10.1038/nm.1789
Edwards SL, Brough R, Lord CJ et al (2008) Resistance to therapy caused by intragenic deletion in BRCA2. Nature 451:1111–1115. https://doi.org/10.1038/nature06548
Formisano L, Lu Y, Servetto A et al (2019) Aberrant FGFR signaling mediates resistance to CDK4/6 inhibitors in ER+ breast cancer. Nat Commun 10:1373. https://doi.org/10.1038/s41467-019-09068-2
Fostira F, Tsitlaidou M, Papadimitriou C et al (2012) Prevalence of BRCA1 mutations among 403 women with triple-negative breast cancer: implications for genetic screening selection criteria: a Hellenic Cooperative Oncology Group Study. Breast Cancer Res Treat 134:353–362. https://doi.org/10.1007/s10549-012-2021-9
Foulkes WD, Smith IE, Reis-Filho JS (2010) Triple-negative breast cancer. N Engl J Med 363:1938–1948. https://doi.org/10.1056/NEJMra1001389
Fribbens C, O’Leary B, Kilburn L et al (2016) Plasma ESR1 mutations and the treatment of estrogen receptor-positive advanced breast cancer. JCO 34:2961–2968. https://doi.org/10.1200/JCO.2016.67.3061
Fribbens C, Murillas IG, Beaney M et al (2018) Tracking evolution of aromatase inhibitor resistance with circulating tumour DNA analysis in metastatic breast cancer. Ann Oncol 29:145–153. https://doi.org/10.1093/annonc/mdx483
Friedel G, Pastorino U, Ginsberg RJ et al (2002) Results of lung metastasectomy from breast cancer: prognostic criteria on the basis of 467 cases of the international registry of lung metastases. Eur J Cardiothorac Surg 22:335–344. https://doi.org/10.1016/S1010-7940(02)00331-7
Garcia-Murillas I, Schiavon G, Weigelt B et al (2015) Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. Sci Transl Med 7:302ra133. https://doi.org/10.1126/scitranslmed.aab0021
Garcia-Murillas I, Chopra N, Comino-Méndez I et al (2019) Assessment of molecular relapse detection in early-stage breast cancer. JAMA Oncol 5:1473–1478. https://doi.org/10.1001/jamaoncol.2019.1838
Gerlinger M, Rowan AJ, Horswell S et al (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366:883–892. https://doi.org/10.1056/NEJMoa1113205
Gevensleben H, Garcia-Murillas I, Graeser MK et al (2013) Noninvasive detection of HER2 amplification with plasma DNA digital PCR. Clin Cancer Res 19:3276–3284. https://doi.org/10.1158/1078-0432.CCR-12-3768
Guan X, Liu B, Niu Y et al (2020) Longitudinal HER2 amplification tracked in circulating tumor DNA for therapeutic effect monitoring and prognostic evaluation in patients with breast cancer. The Breast 49:261–266. https://doi.org/10.1016/j.breast.2019.12.010
Gutiontov SI, Pitroda SP, Weichselbaum RR (2020) Oligometastasis: past, present, future. Int J Radiat Oncol Biol Phys 108:530–538. https://doi.org/10.1016/j.ijrobp.2020.02.019
Hamilton EP, Patel MR, Armstrong AC et al (2018) A first-in-human study of the new oral selective estrogen receptor degrader AZD9496 for ER+/HER2− advanced breast cancer. Clin Cancer Res 24:3510–3518. https://doi.org/10.1158/1078-0432.CCR-17-3102
Herrera-Abreu MT, Palafox M, Asghar U et al (2016) Early adaptation and acquired resistance to CDK4/6 inhibition in estrogen receptor-positive breast cancer. Cancer Res 76:2301–2313. https://doi.org/10.1158/0008-5472.CAN-15-0728
Hortobagyi GN, Stemmer SM, Burris HA et al (2018) Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. Ann Oncol 29:1541–1547. https://doi.org/10.1093/annonc/mdy155
Houssami N, Macaskill P, Balleine RL et al (2011) HER2 discordance between primary breast cancer and its paired metastasis: tumor biology or test artefact? Insights through meta-analysis. Breast Cancer Res Treat 129:659. https://doi.org/10.1007/s10549-011-1632-x
Howlader N, Altekruse SF, Li CI et al (2014) US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst 106:1. https://doi.org/10.1093/jnci/dju055
Hu Y, Ulrich BC, Supplee J et al (2018) False-positive plasma genotyping due to clonal hematopoiesis. Clin Cancer Res 24:4437–4443. https://doi.org/10.1158/1078-0432.CCR-18-0143
Jeselsohn R, Yelensky R, Buchwalter G et al (2014) Emergence of constitutively active estrogen receptor-α mutations in pretreated advanced estrogen receptor-positive breast cancer. Clin Cancer Res 20:1757–1767. https://doi.org/10.1158/1078-0432.CCR-13-2332
Johnston SR, Kilburn LS, Ellis P et al (2013) Fulvestrant plus anastrozole or placebo versus exemestane alone after progression on non-steroidal aromatase inhibitors in postmenopausal patients with hormone-receptor-positive locally advanced or metastatic breast cancer (SoFEA): a composite, multicentre, phase 3 randomised trial. Lancet Oncol 14:989–998. https://doi.org/10.1016/S1470-2045(13)70322-X
Jones RH, Casbard A, Carucci M et al (2020) Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive breast cancer (FAKTION): a multicentre, randomised, controlled, phase 2 trial. Lancet Oncol 21:345–357. https://doi.org/10.1016/S1470-2045(19)30817-4
Juric D, Ciruelos E, Rubovszky G et al (2019) Abstract GS3-08: Alpelisib + fulvestrant for advanced breast cancer: subgroup analyses from the phase III SOLAR-1 trial. Cancer Res 79:GS3-08. https://doi.org/10.1158/1538-7445.SABCS18-GS3-08
Kamps R, Brandão RD, van den Bosch BJ et al (2017) Next-generation sequencing in oncology: genetic diagnosis, risk prediction and cancer classification. Int J Mol Sci 18:308. https://doi.org/10.3390/ijms18020308
Kirn V, Strake L, Thangarajah F et al (2018) ESR1-promoter-methylation status in primary breast cancer and its corresponding metastases. Clin Exp Metastasis 35:707–712. https://doi.org/10.1007/s10585-018-9935-5
Koboldt DC, Fulton RS, McLellan MD et al (2012) Comprehensive molecular portraits of human breast tumours. Nature 490:61–70. https://doi.org/10.1038/nature11412
Krop IE, Mayer IA, Ganju V et al (2016) Pictilisib for oestrogen receptor-positive, aromatase inhibitor-resistant, advanced or metastatic breast cancer (FERGI): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol 17:811–821. https://doi.org/10.1016/S1470-2045(16)00106-6
Lanman RB, Mortimer SA, Zill OA et al (2015) Analytical and clinical validation of a digital sequencing panel for quantitative, highly accurate evaluation of cell-free circulating tumor DNA. PLoS ONE 10:e0140712. https://doi.org/10.1371/journal.pone.0140712
Leary RJ, Sausen M, Kinde I et al (2012) Detection of chromosomal alterations in the circulation of cancer patients with whole-genome sequencing. Sci Transl Med 4:162ra154. https://doi.org/10.1126/scitranslmed.3004742
Lehmann-Werman R, Neiman D, Zemmour H et al (2016) Identification of tissue-specific cell death using methylation patterns of circulating DNA. PNAS 113:E1826–E1834. https://doi.org/10.1073/pnas.1519286113
Lennon AM, Buchanan AH, Kinde I et al (2020) Feasibility of blood testing combined with PET-CT to screen for cancer and guide intervention. Science 369:eabb601. https://doi.org/10.1126/science.abb9601
Leo AD, Johnston S, Lee KS et al (2018) 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 19:87–100. https://doi.org/10.1016/S1470-2045(17)30688-5
Li M, Diehl F, Dressman D et al (2006) BEAMing up for detection and quantification of rare sequence variants. Nat Methods 3:95–97. https://doi.org/10.1038/nmeth850
Litton JK, Rugo HS, Ettl J et al (2018) Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med 379:753–763. https://doi.org/10.1056/NEJMoa1802905
Llombart-Cussac A, Pérez-García JM, Bellet M et al (2020) PARSIFAL: A randomized, multicenter, open-label, phase II trial to evaluate palbociclib in combination with fulvestrant or letrozole in endocrine-sensitive patients with estrogen receptor (ER)[+]/HER2[−] metastatic breast cancer. JCO 38:1007. https://doi.org/10.1200/JCO.2020.38.15_suppl.1007
Luskin MR, Murakami MA, Manalis SR, Weinstock DM (2018) Targeting minimal residual disease: a path to cure? Nat Rev Cancer 18:255–263. https://doi.org/10.1038/nrc.2017.125
Ma CX, Bose R, Gao F et al (2017) Neratinib efficacy and circulating tumor DNA detection of HER2 mutations in HER2 nonamplified metastatic breast cancer. Clin Cancer Res 23:5687–5695. https://doi.org/10.1158/1078-0432.CCR-17-0900
Madic J, Kiialainen A, Bidard F-C et al (2015) Circulating tumor DNA and circulating tumor cells in metastatic triple negative breast cancer patients. Int J Cancer 136:2158–2165. https://doi.org/10.1002/ijc.29265
Magbanua M, Brown-Swigart L, Hirst G et al (2019) Abstract PD2–01: personalized serial circulating tumor DNA (ctDNA) analysis in high-risk early stage breast cancer patients to monitor and predict response to neoadjuvant therapy and outcome in the I-SPY 2 TRIAL. Cancer Res 79:PD2-01. https://doi.org/10.1158/1538-7445.SABCS18-PD2-01
Malone KE, Daling JR, Doody DR et al (2006) 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 66:8297–8308. https://doi.org/10.1158/0008-5472.CAN-06-0503
Martínez-Galán J, Torres-Torres B, Núñez MI et al (2014) ESR1gene 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. https://doi.org/10.1186/1471-2407-14-59
Mastoraki S, Strati A, Tzanikou E et al (2018) ESR1 methylation: a liquid biopsy-based epigenetic assay for the follow-up of patients with metastatic breast cancer receiving endocrine treatment. Clin Cancer Res 24:1500–1510. https://doi.org/10.1158/1078-0432.CCR-17-1181
Masuda N, Lee S-J, Ohtani S et al (2017) Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med 376:2147–2159. https://doi.org/10.1056/NEJMoa1612645
McDonald BR, Contente-Cuomo T, Sammut S-J et al (2019) Personalized circulating tumor DNA analysis to detect residual disease after neoadjuvant therapy in breast cancer. Sci Transl Med 11:eaax7392. https://doi.org/10.1126/scitranslmed.aax7392
Mollon L, Aguilar A, Anderson E et al (2018) Abstract 1207: a systematic literature review of the prevalence of PIK3CA mutations and mutation hotspots in HR+/HER2− metastatic breast cancer. Cancer Res 78:1207. https://doi.org/10.1158/1538-7445.AM2018-1207
Mosele F, Stefanovska B, Lusque A et al (2020) Outcome and molecular landscape of patients with PIK3CA-mutated metastatic breast cancer. Ann Oncol 31:377–386. https://doi.org/10.1016/j.annonc.2019.11.006
Moynahan ME, Chen D, He W et al (2017) Correlation between PIK3CA mutations in cell-free DNA and everolimus efficacy in HR+, HER2− advanced breast cancer: results from BOLERO-2. Br J Cancer 116:726–730. https://doi.org/10.1038/bjc.2017.25
Murtaza M, Dawson S-J, Tsui DWY et al (2013) Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature 497:108–112. https://doi.org/10.1038/nature12065
Nassiri F, Chakravarthy A, Feng S et al (2020) Detection and discrimination of intracranial tumors using plasma cell-free DNA methylomes. Nat Med 26:1044–1047. https://doi.org/10.1038/s41591-020-0932-2
Nayar U, Cohen O, Kapstad C et al (2019) Acquired HER2 mutations in ER + metastatic breast cancer confer resistance to estrogen receptor–directed therapies. Nat Genet 51:207–216. https://doi.org/10.1038/s41588-018-0287-5
Newman AM, Bratman SV, To J et al (2014) An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nat Med 20:548–554. https://doi.org/10.1038/nm.3519
Niikura N, Liu J, Hayashi N et al (2012) Loss of human epidermal growth factor receptor 2 (HER2) expression in metastatic sites of HER2-overexpressing primary breast tumors. JCO 30:593–599. https://doi.org/10.1200/JCO.2010.33.8889
O’Leary B, Cutts RJ, Liu Y et al (2018a) The genetic landscape and clonal evolution of breast cancer resistance to palbociclib plus fulvestrant in the PALOMA-3 trial. Cancer Discov 8:1390–1403. https://doi.org/10.1158/2159-8290.CD-18-0264
O’Leary B, Hrebien S, Morden JP et al (2018b) Early circulating tumor DNA dynamics and clonal selection with palbociclib and fulvestrant for breast cancer. Nat Commun 9:896. https://doi.org/10.1038/s41467-018-03215-x
Osborne CK, Wakeling A, Nicholson RI (2004) Fulvestrant: an oestrogen receptor antagonist with a novel mechanism of action. Br J Cancer 90:S2–S6. https://doi.org/10.1038/sj.bjc.6601629
Palma DA, Olson R, Harrow S et al (2019) Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial. The Lancet 393:2051–2058. https://doi.org/10.1016/S0140-6736(18)32487-5
Paoletti C, Schiavon G, Dolce EM et al (2018) Circulating biomarkers and resistance to endocrine therapy in metastatic breast cancers: correlative results from AZD9496 oral SERD phase I trial. Clin Cancer Res 24:5860–5872. https://doi.org/10.1158/1078-0432.CCR-18-1569
Perakis S, Speicher MR (2017) Emerging concepts in liquid biopsies. BMC Med 15:75. https://doi.org/10.1186/s12916-017-0840-6
Radovich M, Jiang G, Hancock BA et al (2020) Association of circulating tumor DNA and circulating tumor cells after neoadjuvant chemotherapy with disease recurrence in patients with triple-negative breast cancer: preplanned secondary analysis of the BRE12-158 randomized clinical trial. JAMA Oncol 6:1410–1415. https://doi.org/10.1001/jamaoncol.2020.2295
Riva F, Bidard F-C, Houy A et al (2017) Patient-specific circulating tumor DNA detection during neoadjuvant chemotherapy in triple-negative breast cancer. Clin Chem 63:691–699. https://doi.org/10.1373/clinchem.2016.262337
Robinson DR, Wu Y-M, Vats P et al (2013) Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet 45:1446–1451. https://doi.org/10.1038/ng.2823
Robson M, Im S-A, Senkus E et al (2017) Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med 377:523–533. https://doi.org/10.1056/NEJMoa1706450
Rothé F, Silva MJ, Venet D et al (2019) Circulating tumor DNA in HER2-amplified breast cancer: a translational research substudy of the NeoALTTO Phase III Trial. Clin Cancer Res 25:3581. https://doi.org/10.1158/1078-0432.CCR-18-2521
Sakai W, Swisher EM, Karlan BY et al (2008) Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers. Nature 451:1116–1120. https://doi.org/10.1038/nature06633
Schiavon G, Hrebien S, Garcia-Murillas I et al (2015) Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer. Sci Transl Med 7:313ra182. https://doi.org/10.1126/scitranslmed.aac7551
Schwarzenbach H, Hoon DSB, Pantel K (2011) Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer 11:426–437. https://doi.org/10.1038/nrc3066
Singh RR (2020) Next-generation sequencing in high-sensitive detection of mutations in tumors: challenges, advances, and applications. J Mol Diagn 22:994–1007. https://doi.org/10.1016/j.jmoldx.2020.04.213
Slamon DJ, Leyland-Jones B, Shak S et al (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344:783–792. https://doi.org/10.1056/NEJM200103153441101
Spoerke JM, Gendreau S, Walter K et al (2016) Heterogeneity and clinical significance of ESR1 mutations in ER-positive metastatic breast cancer patients receiving fulvestrant. Nat Commun 7:11579. https://doi.org/10.1038/ncomms11579
Spring LM, Fell G, Arfe A et al (2020) Pathologic complete response after neoadjuvant chemotherapy and impact on breast cancer recurrence and survival: a comprehensive meta-analysis. Clin Cancer Res 26:2838–2848. https://doi.org/10.1158/1078-0432.CCR-19-3492
Stemke-Hale K, Gonzalez-Angulo AM, Lluch A et al (2008) An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer. Cancer Res 68:6084–6091. https://doi.org/10.1158/0008-5472.CAN-07-6854
Swain SM, Kim S-B, Cortés J et al (2013) Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol 14:461–471. https://doi.org/10.1016/S1470-2045(13)70130-X
Toy W, Weir H, Razavi P et al (2017) Activating ESR1 mutations differentially affect the efficacy of ER antagonists. Cancer Discov 7:277–287. https://doi.org/10.1158/2159-8290.CD-15-1523
Turner NC, Reis-Filho JS (2012) Genetic heterogeneity and cancer drug resistance. Lancet Oncol 13:e178–e185. https://doi.org/10.1016/S1470-2045(11)70335-7
Turner NC, Ro J, André F et al (2015) Palbociclib in hormone-receptor-positive advanced breast cancer. N Engl J Med 373:209–219. https://doi.org/10.1056/NEJMoa1505270
Turner NC, Swift C, Kilburn L et al (2020a) ESR1 mutations and overall survival on fulvestrant versus exemestane in advanced hormone receptor-positive breast cancer: a combined analysis of the phase III SoFEA and EFECT trials. Clin Cancer Res 26:5172–5177. https://doi.org/10.1158/1078-0432.CCR-20-0224
Turner NC, Kingston B, Kilburn LS et al (2020b) Circulating tumour DNA analysis to direct therapy in advanced breast cancer (plasmaMATCH): a multicentre, multicohort, phase 2a, platform trial. Lancet Oncol 21:1296–1308. https://doi.org/10.1016/S1470-2045(20)30444-7
Verma S, Miles D, Gianni L et al (2012) Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 367:1783–1791. https://doi.org/10.1056/NEJMoa1209124
von Minckwitz G, Huang C-S, Mano MS et al (2018) Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med 380:617–628. https://doi.org/10.1056/NEJMoa1814017
Waks AG, Winer EP (2019) Breast cancer treatment: a review. JAMA 321:288–300. https://doi.org/10.1001/jama.2018.19323
Weichselbaum RR, Hellman S (2011) Oligometastases revisited. Nat Rev Clin Oncol 8:378–382. https://doi.org/10.1038/nrclinonc.2011.44
Weigelt B, Comino-Méndez I, de Bruijn I et al (2017) Diverse BRCA1 and BRCA2 reversion mutations in circulating cell-free DNA of therapy-resistant breast or ovarian cancer. Clin Cancer Res 23:6708–6720. https://doi.org/10.1158/1078-0432.CCR-17-0544
Wolff AC, Hammond MEH, Hicks DG et al (2014) 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. Arch Pathol Lab Med 138:241–256. https://doi.org/10.5858/arpa.2013-0953-SA
Xie M, Lu C, Wang J et al (2014) Age-related mutations associated with clonal hematopoietic expansion and malignancies. Nat Med 20:1472–1478. https://doi.org/10.1038/nm.3733
Zhang Q-X, Borg Å, Wolf DM et al (1997) An estrogen receptor mutant with strong hormone-independent activity from a metastatic breast cancer. Cancer Res 57:1244–1249
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Chan, J.C.H., Chow, J.C.H., Ho, C.H.M. et al. Clinical application of circulating tumor DNA in breast cancer. J Cancer Res Clin Oncol 147, 1431–1442 (2021). https://doi.org/10.1007/s00432-021-03588-5
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DOI: https://doi.org/10.1007/s00432-021-03588-5