Clinical significance of liquid biopsy in neoadjuvant therapy of breast cancer_West China Medical Journal

Authors：

HE Ping , WU Yanqi ,  LUO Ting

Department of Head and Neck Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

LUO Ting, Email: tina621@163.com

Keywords：

Breast cancer; circulating tumor cells; circulating tumor DNA; liquid biopsy; neoadjuvant therapy

DOI：

10.7507/1002-0179.202107172

Video：

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Abstract Full text Figures/Tables Video References Cited by

The important detection indicators of liquid biopsy in cancer patients include circulating tumor cells and circulating tumor DNA. The former refers to the cells that fall off from the primary tumor and metastatic sites and enter the blood circulation through blood vessels or lymphatic vessels, while the latter refers to the cell-free DNA released into the blood vessels by apoptotic or necrotic tumor cells. For breast cancer patients receiving neoadjuvant therapy, dynamic monitoring of circulating tumor cells and circulating tumor DNA can help early identify the responsiveness of tumor patients to different treatments and guide subsequent treatments to improve prognosis. This article reviews the research progress and clinical significance of detecting circulating tumor cells and circulating tumor DNA in breast cancer patients receiving neoadjuvant therapy, aiming to provide a reference for the more rational application of circulating tumor cells and circulating tumor DNA in neoadjuvant therapy of breast cancer.

Citation： HE Ping, WU Yanqi, LUO Ting. Clinical significance of liquid biopsy in neoadjuvant therapy of breast cancer. West China Medical Journal, 2022, 37(6): 945-950. doi: 10.7507/1002-0179.202107172 Copy

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2.	Harbeck N, Gnant M. Breast cancer. Lancet, 2017, 389(10074): 1134-1150.
3.	中国临床肿瘤学会指南工作委员会. 中国临床肿瘤学会(CSCO)乳腺癌诊疗指南 2021. 北京: 人民卫生出版社, 2021.
4.	Bonnefoi H, Litière S, Piccart M, et al. Pathological complete response after neoadjuvant chemotherapy is an independent predictive factor irrespective of simplified breast cancer intrinsic subtypes: a landmark and two-step approach analyses from the EORTC 10994/BIG 1-00 phase Ⅲ trial. Ann Oncol, 2014, 25(6): 1128-1136.
5.	Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet, 2014, 384(9938): 164-172.
6.	Asaoka M, Narui K, Suganuma N, et al. Clinical and pathological predictors of recurrence in breast cancer patients achieving pathological complete response to neoadjuvant chemotherapy. Eur J Surg Oncol, 2019, 45(12): 2289-2294.
7.	Fei F, Messina C, Slaets L, et al. Tumour size is the only predictive factor of distant recurrence after pathological complete response to neoadjuvant chemotherapy in patients with large operable or locally advanced breast cancers: a sub-study of EORTC 10994/BIG 1-00 phase Ⅲ trial. Eur J Cancer, 2015, 51(3): 301-309.
8.	李健斌, 江泽飞. 2019 年 CSCO BC 指南更新要点解读. 中国肿瘤外科杂志, 2019, 11(3): 155-160.
9.	Bidard FC, Proudhon C, Pierga JY. Circulating tumor cells in breast cancer. Mol Oncol, 2016, 10(3): 418-430.
10.	Diamantopoulou Z, Castro-Giner F, Aceto N. Circulating tumor cells: ready for translation?. J Exp Med, 2020, 217(8): e20200356.
11.	Rushton AJ, Nteliopoulos G, Shaw JA, et al. A review of circulating tumour cell enrichment technologies. Cancers (Basel), 2021, 13(5): 970.
12.	United States Food and Drug Administration. 510(k) premarket notification. (2008-02-26)[2021-07-20]. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/pmn.cfm?ID=K073338.
13.	Andergassen U, K?lbl AC, Hutter S, et al. Detection of circulating tumour cells from blood of breast cancer patients via RT-qPCR. Cancers (Basel), 2013, 5(4): 1212-1220.
14.	Andreopoulou E, Yang LY, Rangel KM, et al. Comparison of assay methods for detection of circulating tumor cells in metastatic breast cancer: AdnaGen AdnaTest BreastCancer Select/Detect? versus Veridex CellSearch? system. Int J Cancer, 2012, 130(7): 1590-1597.
15.	Egner JR. AJCC cancer staging manual. JAMA, 2010, 304(15): 1726-1727.
16.	Cristofanilli M, Budd GT, Ellis MJ, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med, 2004, 351(8): 781-791.
17.	Smerage JB, Barlow WE, Hortobagyi GN, et al. Circulating tumor cells and response to chemotherapy in metastatic breast cancer: SWOG S0500. J Clin Oncol, 2014, 32(31): 3483-3489.
18.	Bidard FC, Michiels S, Riethdorf S, et al. Circulating tumor cells in breast cancer patients treated by neoadjuvant chemotherapy: a meta-analysis. J Natl Cancer Inst, 2018, 110(6): 560-567.
19.	Janni WJ, Rack B, Terstappen LW, et al. Pooled analysis of the prognostic relevance of circulating tumor cells in primary breast cancer. Clin Cancer Res, 2016, 22(10): 2583-2593.
20.	Pierga JY, Bidard FC, Mathiot C, et al. Circulating tumor cell detection predicts early metastatic relapse after neoadjuvant chemotherapy in large operable and locally advanced breast cancer in a phase Ⅱ randomized trial. Clin Cancer Res, 2008, 14(21): 7004-7010.
21.	Bidard FC, Mathiot C, Delaloge S, et al. Single circulating tumor cell detection and overall survival in nonmetastatic breast cancer. Ann Oncol, 2010, 21(4): 729-733.
22.	Riethdorf S, Müller V, Zhang L, et al. Detection and HER2 expression of circulating tumor cells: prospective monitoring in breast cancer patients treated in the neoadjuvant GeparQuattro trial. Clin Cancer Res, 2010, 16(9): 2634-2645.
23.	Ni C, Shen Y, Fang Q, et al. Prospective study of the relevance of circulating tumor cell status and neoadjuvant chemotherapy effectiveness in early breast cancer. Cancer Med, 2020, 9(7): 2290-2298.
24.	O’Toole SA, Spillane C, Huang Y, et al. Circulating tumour cell enumeration does not correlate with Miller-Payne grade in a cohort of breast cancer patients undergoing neoadjuvant chemotherapy. Breast Cancer Res Treat, 2020, 181(3): 571-580.
25.	Serrano MJ, Rovira PS, Martínez-Zubiaurre I, et al. Dynamics of circulating tumor cells in early breast cancer under neoadjuvant therapy. Exp Ther Med, 2012, 4(1): 43-48.
26.	Hall C, Karhade M, Laubacher B, et al. Circulating tumor cells after neoadjuvant chemotherapy in stage Ⅰ-Ⅲ triple-negative breast cancer. Ann Surg Oncol, 2015, 22(Suppl 3): S552-S558.
27.	Lucci A, Hall CS, Lodhi AK, et al. Circulating tumour cells in non-metastatic breast cancer: a prospective study. Lancet Oncol, 2012, 13(7): 688-695.
28.	Fei F, Du Y, Di G, et al. Are changes in circulating tumor cell (CTC) count associated with the response to neoadjuvant chemotherapy in local advanced breast cancer? A meta-analysis. Oncol Res Treat, 2014, 37(5): 250-254.
29.	Kwan TT, Bardia A, Spring LM, et al. A digital RNA signature of circulating tumor cells predicting early therapeutic response in localized and metastatic breast cancer. Cancer Discov, 2018, 8(10): 1286-1299.
30.	Davis AA, Cristofanilli M. Minimal residual disease in patients with nonmetastatic triple-negative breast cancer: positive, negative, or a more complex issue?. JAMA Oncol, 2020, 6(9): 1332-1333.
31.	Kaigorodova EV, Savelieva OE, Tashireva LA, et al. Heterogeneity of circulating tumor cells in neoadjuvant chemotherapy of breast cancer. Molecules, 2018, 23(4): 727.
32.	Mego M, Mani SA, Lee BN, et al. Expression of epithelial-mesenchymal transition-inducing transcription factors in primary breast cancer: the effect of neoadjuvant therapy. Int J Cancer, 2012, 130(4): 808-816.
33.	Hattori M, Nakanishi H, Yoshimura M, et al. Circulating tumor cells detection in tumor draining vein of breast cancer patients. Sci Rep, 2019, 9(1): 18195.
34.	Riethdorf S, Müller V, Loibl S, et al. Prognostic impact of circulating tumor cells for breast cancer patients treated in the neoadjuvant “geparquattro” trial. Clin Cancer Res, 2017, 23(18): 5384-5393.
35.	Radovich M, Jiang G, Hancock BA, et al. 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, 2020, 6(9): 1410-1415.
36.	Hall CS, Karhade MG, Bowman Bauldry JB, et al. Prognostic value of circulating tumor cells identified before surgical resection in nonmetastatic breast cancer patients. J Am Coll Surg, 2016, 223(1): 20-29.
37.	Yan WT, Cui X, Chen Q, et al. Circulating tumor cell status monitors the treatment responses in breast cancer patients: a meta-analysis. Sci Rep, 2017, 7: 43464.
38.	Pierga JY, Bidard FC, Autret A, et al. Circulating tumour cells and pathological complete response: independent prognostic factors in inflammatory breast cancer in a pooled analysis of two multicentre phase Ⅱ trials (BEVERLY-1 and -2) of neoadjuvant chemotherapy combined with bevacizumab. Ann Oncol, 2017, 28(1): 103-109.
39.	Kasimir-Bauer S, Bittner AK, König L, et al. Does primary neoadjuvant systemic therapy eradicate minimal residual disease? Analysis of disseminated and circulating tumor cells before and after therapy. Breast Cancer Res, 2016, 18(1): 20.
40.	Jahr S, Hentze H, Englisch S, et al. DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res, 2001, 61(4): 1659-1665.
41.	Chen YH, Hancock BA, Solzak JP, et al. Next-generation sequencing of circulating tumor DNA to predict recurrence in triple-negative breast cancer patients with residual disease after neoadjuvant chemotherapy. NPJ Breast Cancer, 2017, 3: 24.
42.	McDonald BR, Contente-Cuomo T, Sammut SJ, et al. Personalized circulating tumor DNA analysis to detect residual disease after neoadjuvant therapy in breast cancer. Sci Transl Med, 2019, 11(504): eaax7392.
43.	Riva F, Bidard FC, Houy A, et al. Patient-specific circulating tumor DNA detection during neoadjuvant chemotherapy in triple-negative breast cancer. Clin Chem, 2017, 63(3): 691-699.
44.	Cirmena G, Garuti A, De Mariano M, et al. Circulating tumor DNA using tagged targeted deep sequencing to assess minimal residual disease in breast cancer patients undergoing neoadjuvant chemotherapy. J Oncol, 2020, 2020: 8132507.
45.	Merker JD, Oxnard GR, Compton C, 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, 2018, 36(16): 1631-1641.
46.	Rothé F, Silva MJ, Venet D, et al. Circulating tumor DNA in HER2-amplified breast cancer: a translational research substudy of the NeoALTTO phase Ⅲ trial. Clin Cancer Res, 2019, 25(12): 3581-3588.
47.	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, 2019, 25(21): 6546-6553.
48.	Garcia-Murillas I, Schiavon G, Weigelt B, et al. Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. Sci Transl Med, 2015, 7(302): 302ra133.
49.	Magbanua MJM, Swigart LB, Wu HT, et al. Circulating tumor DNA in neoadjuvant-treated breast cancer reflects response and survival. Ann Oncol, 2021, 32(2): 229-239.
50.	Li S, Lai H, Liu J, et al. Circulating tumor DNA predicts the response and prognosis in patients with early breast cancer receiving neoadjuvant chemotherapy. JCO Precis Oncol, 2020, 4: PO.19.00292.
51.	Magbanua MJM, Li W, Wolf DM, et al. Circulating tumor DNA and magnetic resonance imaging to predict neoadjuvant chemotherapy response and recurrence risk. NPJ Breast Cancer, 2021, 7(1): 32.
52.	Zhou Y, Xu Y, Wang C, et al. Serial circulating tumor DNA identification associated with the efficacy and prognosis of neoadjuvant chemotherapy in breast cancer. Breast Cancer Res Treat, 2021, 188(3): 661-673.
53.	Ortolan E, Appierto V, Silvestri M, et al. Blood-based genomics of triple-negative breast cancer progression in patients treated with neoadjuvant chemotherapy. ESMO Open, 2021, 6(2): 100086.
54.	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, 2017, 17(1): 61-69.e3.
55.	Rugo HS, Olopade OI, DeMichele A, et al. Adaptive randomization of veliparib-carboplatin treatment in breast cancer. N Engl J Med, 2016, 375(1): 23-34.
56.	Garcia-Murillas I, Chopra N, Comino-Méndez I, et al. Assessment of molecular relapse detection in early-stage breast cancer. JAMA Oncol, 2019, 5(10): 1473-1478.
57.	Institute of Cancer Research. A trial using ctDNA blood tests to detect cancer cells after standard treatment to trigger additional treatment in early stage triple negative breast cancer patients (c-TRAK-TN). (2022-02-24)[2022-04-15]. https://www.clinicaltrials.gov/ct2/show/NCT03145961.

1. Vaidya JS, Massarut S, Vaidya HJ, et al. Rethinking neoadjuvant chemotherapy for breast cancer. BMJ, 2018, 360: j5913.
2. Harbeck N, Gnant M. Breast cancer. Lancet, 2017, 389(10074): 1134-1150.
3. 中国临床肿瘤学会指南工作委员会. 中国临床肿瘤学会(CSCO)乳腺癌诊疗指南 2021. 北京: 人民卫生出版社, 2021.
4. Bonnefoi H, Litière S, Piccart M, et al. Pathological complete response after neoadjuvant chemotherapy is an independent predictive factor irrespective of simplified breast cancer intrinsic subtypes: a landmark and two-step approach analyses from the EORTC 10994/BIG 1-00 phase Ⅲ trial. Ann Oncol, 2014, 25(6): 1128-1136.
5. Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet, 2014, 384(9938): 164-172.
6. Asaoka M, Narui K, Suganuma N, et al. Clinical and pathological predictors of recurrence in breast cancer patients achieving pathological complete response to neoadjuvant chemotherapy. Eur J Surg Oncol, 2019, 45(12): 2289-2294.
7. Fei F, Messina C, Slaets L, et al. Tumour size is the only predictive factor of distant recurrence after pathological complete response to neoadjuvant chemotherapy in patients with large operable or locally advanced breast cancers: a sub-study of EORTC 10994/BIG 1-00 phase Ⅲ trial. Eur J Cancer, 2015, 51(3): 301-309.
8. 李健斌, 江泽飞. 2019 年 CSCO BC 指南更新要点解读. 中国肿瘤外科杂志, 2019, 11(3): 155-160.
9. Bidard FC, Proudhon C, Pierga JY. Circulating tumor cells in breast cancer. Mol Oncol, 2016, 10(3): 418-430.
10. Diamantopoulou Z, Castro-Giner F, Aceto N. Circulating tumor cells: ready for translation?. J Exp Med, 2020, 217(8): e20200356.
11. Rushton AJ, Nteliopoulos G, Shaw JA, et al. A review of circulating tumour cell enrichment technologies. Cancers (Basel), 2021, 13(5): 970.
12. United States Food and Drug Administration. 510(k) premarket notification. (2008-02-26)[2021-07-20]. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/pmn.cfm?ID=K073338.
13. Andergassen U, K?lbl AC, Hutter S, et al. Detection of circulating tumour cells from blood of breast cancer patients via RT-qPCR. Cancers (Basel), 2013, 5(4): 1212-1220.
14. Andreopoulou E, Yang LY, Rangel KM, et al. Comparison of assay methods for detection of circulating tumor cells in metastatic breast cancer: AdnaGen AdnaTest BreastCancer Select/Detect? versus Veridex CellSearch? system. Int J Cancer, 2012, 130(7): 1590-1597.
15. Egner JR. AJCC cancer staging manual. JAMA, 2010, 304(15): 1726-1727.
16. Cristofanilli M, Budd GT, Ellis MJ, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med, 2004, 351(8): 781-791.
17. Smerage JB, Barlow WE, Hortobagyi GN, et al. Circulating tumor cells and response to chemotherapy in metastatic breast cancer: SWOG S0500. J Clin Oncol, 2014, 32(31): 3483-3489.
18. Bidard FC, Michiels S, Riethdorf S, et al. Circulating tumor cells in breast cancer patients treated by neoadjuvant chemotherapy: a meta-analysis. J Natl Cancer Inst, 2018, 110(6): 560-567.
19. Janni WJ, Rack B, Terstappen LW, et al. Pooled analysis of the prognostic relevance of circulating tumor cells in primary breast cancer. Clin Cancer Res, 2016, 22(10): 2583-2593.
20. Pierga JY, Bidard FC, Mathiot C, et al. Circulating tumor cell detection predicts early metastatic relapse after neoadjuvant chemotherapy in large operable and locally advanced breast cancer in a phase Ⅱ randomized trial. Clin Cancer Res, 2008, 14(21): 7004-7010.
21. Bidard FC, Mathiot C, Delaloge S, et al. Single circulating tumor cell detection and overall survival in nonmetastatic breast cancer. Ann Oncol, 2010, 21(4): 729-733.
22. Riethdorf S, Müller V, Zhang L, et al. Detection and HER2 expression of circulating tumor cells: prospective monitoring in breast cancer patients treated in the neoadjuvant GeparQuattro trial. Clin Cancer Res, 2010, 16(9): 2634-2645.
23. Ni C, Shen Y, Fang Q, et al. Prospective study of the relevance of circulating tumor cell status and neoadjuvant chemotherapy effectiveness in early breast cancer. Cancer Med, 2020, 9(7): 2290-2298.
24. O’Toole SA, Spillane C, Huang Y, et al. Circulating tumour cell enumeration does not correlate with Miller-Payne grade in a cohort of breast cancer patients undergoing neoadjuvant chemotherapy. Breast Cancer Res Treat, 2020, 181(3): 571-580.
25. Serrano MJ, Rovira PS, Martínez-Zubiaurre I, et al. Dynamics of circulating tumor cells in early breast cancer under neoadjuvant therapy. Exp Ther Med, 2012, 4(1): 43-48.
26. Hall C, Karhade M, Laubacher B, et al. Circulating tumor cells after neoadjuvant chemotherapy in stage Ⅰ-Ⅲ triple-negative breast cancer. Ann Surg Oncol, 2015, 22(Suppl 3): S552-S558.
27. Lucci A, Hall CS, Lodhi AK, et al. Circulating tumour cells in non-metastatic breast cancer: a prospective study. Lancet Oncol, 2012, 13(7): 688-695.
28. Fei F, Du Y, Di G, et al. Are changes in circulating tumor cell (CTC) count associated with the response to neoadjuvant chemotherapy in local advanced breast cancer? A meta-analysis. Oncol Res Treat, 2014, 37(5): 250-254.
29. Kwan TT, Bardia A, Spring LM, et al. A digital RNA signature of circulating tumor cells predicting early therapeutic response in localized and metastatic breast cancer. Cancer Discov, 2018, 8(10): 1286-1299.
30. Davis AA, Cristofanilli M. Minimal residual disease in patients with nonmetastatic triple-negative breast cancer: positive, negative, or a more complex issue?. JAMA Oncol, 2020, 6(9): 1332-1333.
31. Kaigorodova EV, Savelieva OE, Tashireva LA, et al. Heterogeneity of circulating tumor cells in neoadjuvant chemotherapy of breast cancer. Molecules, 2018, 23(4): 727.
32. Mego M, Mani SA, Lee BN, et al. Expression of epithelial-mesenchymal transition-inducing transcription factors in primary breast cancer: the effect of neoadjuvant therapy. Int J Cancer, 2012, 130(4): 808-816.
33. Hattori M, Nakanishi H, Yoshimura M, et al. Circulating tumor cells detection in tumor draining vein of breast cancer patients. Sci Rep, 2019, 9(1): 18195.
34. Riethdorf S, Müller V, Loibl S, et al. Prognostic impact of circulating tumor cells for breast cancer patients treated in the neoadjuvant “geparquattro” trial. Clin Cancer Res, 2017, 23(18): 5384-5393.
35. Radovich M, Jiang G, Hancock BA, et al. 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, 2020, 6(9): 1410-1415.
36. Hall CS, Karhade MG, Bowman Bauldry JB, et al. Prognostic value of circulating tumor cells identified before surgical resection in nonmetastatic breast cancer patients. J Am Coll Surg, 2016, 223(1): 20-29.
37. Yan WT, Cui X, Chen Q, et al. Circulating tumor cell status monitors the treatment responses in breast cancer patients: a meta-analysis. Sci Rep, 2017, 7: 43464.
38. Pierga JY, Bidard FC, Autret A, et al. Circulating tumour cells and pathological complete response: independent prognostic factors in inflammatory breast cancer in a pooled analysis of two multicentre phase Ⅱ trials (BEVERLY-1 and -2) of neoadjuvant chemotherapy combined with bevacizumab. Ann Oncol, 2017, 28(1): 103-109.
39. Kasimir-Bauer S, Bittner AK, König L, et al. Does primary neoadjuvant systemic therapy eradicate minimal residual disease? Analysis of disseminated and circulating tumor cells before and after therapy. Breast Cancer Res, 2016, 18(1): 20.
40. Jahr S, Hentze H, Englisch S, et al. DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res, 2001, 61(4): 1659-1665.
41. Chen YH, Hancock BA, Solzak JP, et al. Next-generation sequencing of circulating tumor DNA to predict recurrence in triple-negative breast cancer patients with residual disease after neoadjuvant chemotherapy. NPJ Breast Cancer, 2017, 3: 24.
42. McDonald BR, Contente-Cuomo T, Sammut SJ, et al. Personalized circulating tumor DNA analysis to detect residual disease after neoadjuvant therapy in breast cancer. Sci Transl Med, 2019, 11(504): eaax7392.
43. Riva F, Bidard FC, Houy A, et al. Patient-specific circulating tumor DNA detection during neoadjuvant chemotherapy in triple-negative breast cancer. Clin Chem, 2017, 63(3): 691-699.
44. Cirmena G, Garuti A, De Mariano M, et al. Circulating tumor DNA using tagged targeted deep sequencing to assess minimal residual disease in breast cancer patients undergoing neoadjuvant chemotherapy. J Oncol, 2020, 2020: 8132507.
45. Merker JD, Oxnard GR, Compton C, 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, 2018, 36(16): 1631-1641.
46. Rothé F, Silva MJ, Venet D, et al. Circulating tumor DNA in HER2-amplified breast cancer: a translational research substudy of the NeoALTTO phase Ⅲ trial. Clin Cancer Res, 2019, 25(12): 3581-3588.
47. 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, 2019, 25(21): 6546-6553.
48. Garcia-Murillas I, Schiavon G, Weigelt B, et al. Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. Sci Transl Med, 2015, 7(302): 302ra133.
49. Magbanua MJM, Swigart LB, Wu HT, et al. Circulating tumor DNA in neoadjuvant-treated breast cancer reflects response and survival. Ann Oncol, 2021, 32(2): 229-239.
50. Li S, Lai H, Liu J, et al. Circulating tumor DNA predicts the response and prognosis in patients with early breast cancer receiving neoadjuvant chemotherapy. JCO Precis Oncol, 2020, 4: PO.19.00292.
51. Magbanua MJM, Li W, Wolf DM, et al. Circulating tumor DNA and magnetic resonance imaging to predict neoadjuvant chemotherapy response and recurrence risk. NPJ Breast Cancer, 2021, 7(1): 32.
52. Zhou Y, Xu Y, Wang C, et al. Serial circulating tumor DNA identification associated with the efficacy and prognosis of neoadjuvant chemotherapy in breast cancer. Breast Cancer Res Treat, 2021, 188(3): 661-673.
53. Ortolan E, Appierto V, Silvestri M, et al. Blood-based genomics of triple-negative breast cancer progression in patients treated with neoadjuvant chemotherapy. ESMO Open, 2021, 6(2): 100086.
54. 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, 2017, 17(1): 61-69.e3.
55. Rugo HS, Olopade OI, DeMichele A, et al. Adaptive randomization of veliparib-carboplatin treatment in breast cancer. N Engl J Med, 2016, 375(1): 23-34.
56. Garcia-Murillas I, Chopra N, Comino-Méndez I, et al. Assessment of molecular relapse detection in early-stage breast cancer. JAMA Oncol, 2019, 5(10): 1473-1478.
57. Institute of Cancer Research. A trial using ctDNA blood tests to detect cancer cells after standard treatment to trigger additional treatment in early stage triple negative breast cancer patients (c-TRAK-TN). (2022-02-24)[2022-04-15]. https://www.clinicaltrials.gov/ct2/show/NCT03145961.

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