循环肿瘤DNA在乳腺癌内分泌治疗耐药中的应用

doi:10.3760/cma.j.issn.1673-422X.2017.10.014

摘要/Abstract

摘要： 内分泌治疗可以让绝大多数雌激素受体阳性乳腺癌患者受益，但随着内分泌治疗的进行，很多患者不可避免地出现内分泌耐药。在治疗过程中，持续监测耐药突变情况将为临床治疗提供巨大的帮助。循环肿瘤DNA（ctDNA）以其无创、方便、快速及反映肿瘤整体情况等优势引起了人们的注意。新一代测序和微滴数字PCR技术相继成熟，使耐药突变监测系统的建立成为了可能。

关键词: 乳腺肿瘤, 内分泌治疗, 循环肿瘤DNA

Abstract: Although most hormonereceptor positive breast cancer patients initially respond to endocrine treatment, they will eventually acquire resistance to endocrine therapy. Therefore, during clinical treatment, it is of great importance to continuously monitor for resistant mutations. Circulating tumor DNA (ctDNA) has become more prevalent because it is noninvasive, convenient, rapid, and can quickly assess the overall situation of the tumor. With the maturity of nextgeneration sequencing (NGS) and droplet digital polymerase chain reaction (ddPCR), the establishment of endocrine treatment resistance mutation monitoring system has become possible.

Key words: Breast neoplasms, Endocrine therapy, Circulating tumor DNA

刘斌亮,马飞,曾益新. 循环肿瘤DNA在乳腺癌内分泌治疗耐药中的应用[J]. 国际肿瘤学杂志, 2017, 44(10): 779-782.

Liu Binliang, Ma Fei, Zeng Yixin. Application of circulating tumor DNA in endocrine therapy resistance of breast cancer[J]. Journal of International Oncology, 2017, 44(10): 779-782.

参考文献

［1］ Toy W, Shen Y, Won H, et al. ESR1 ligandbinding domain mutations in hormoneresistant breast cancer［J］. Nat Genet, 2013, 45(12): 14391445. DOI: 10.1038/ng.2822. ［2］ Takeshita T, Yamamoto Y, YamamotoIbusuki M, et al. Clinical significance of monitoring ESR1 mutations in circulating cellfree DNA in estrogen receptor positive breast cancer patients［J］. Oncotarget, 2016, 7(22): 3250432518. DOI: 10.18632/oncotarget.8839. ［3］ Selli C, Dixon JM, Sims AH. Accurate prediction of response to endocrine therapy in breast cancer patients: current and future biomarkers［J］. Breast Cancer Res, 2016, 18(1): 118. DOI: 10.1186/s1305801607790. ［4］ Lu J, Mceachern D, Li S, et al. Reactivation of p53 by MDM2 inhibitor MI77301 for the treatment of endocrineresistant breast cancer［J］. Mol Cancer Ther, 2016, 15(12): 28872893. DOI: 10.1158/15357163.MCT160028. ［5］ Musgrove EA, Caldon CE, Barraclough J, et al. Cyclin D as a therapeutic target in cancer［J］. Nat Rev Cancer, 2011, 11(8): 558572. DOI: 10.1038/nrc3090. ［6］ Ma CX, Reinert T, Chmielewska I, et al. Mechanisms of aromatase inhibitor resistance［J］. Nat Rev Cancer, 2015, 15(5): 261275. DOI: 10.1038/nrc3920. ［7］ Liu B, Yang Y, Yi Z, et al. The application of estrogen receptor1 mutations′ detection through circulating tumor dna in breast cancer［J］. Cancer Trans Med, 2017, 3(2): 46. DOI: 10.4103/ctm.ctm_10_17. ［8］ Bidard FC, Fehm T, Ignatiadis M, et al. Clinical application of circulating tumor cells in breast cancer: overview of the current interventional trials［J］. Cancer Metastasis Rev, 2013, 32(12): 179188. DOI: 10.1007/s1055501293980. ［9］ Canzoniero JV, Park BH. Use of cell free DNA in breast oncology［J］. Biochim Biophys Acta, 2016, 1865(2): 266274. DOI: 10.1016/j.bbcan.2016.03.006. ［10］ Schmitt MW, Kennedy SR, Salk JJ, et al. From the cover: detection of ultrarare mutations by nextgeneration sequencing［J］. Proc Natl Acad Sci USA, 2012, 109(36): 1450814513. DOI: 10.1073/pnas.1208715109. ［11］ Hindson CM, Chevillet JR, Briggs HA, et al. Absolute quantification by droplet digital PCR versus analog realtime PCR［J］. Nat Methods, 2013, 10(10): 10031005. DOI: 10.1038/nmeth.2633. ［12］ Chu D, Paoletti C, Gersch C, et al. ESR1 mutations in circulating plasma tumor DNA from metastatic breast cancer patients［J］. Clin Cancer Res, 2016, 22(4): 993999. DOI: 10.1158/10780432.CCR150943. ［13］ Massihnia D, Perez A, Bazan V, et al. A headlight on liquid biopsies: a challenging tool for breast cancer management［J］. Tumour Biol, 2016, 37(4): 42634273. DOI: 10.1007/s132770164856x. ［14］ Liang DH, Ensor JE, Liu ZB, et al. Cellfree DNA as a molecular tool for monitoring disease progression and response to therapy in breast cancer patients［J］. Breast Cancer Res Treat, 2016, 155(1): 139149. DOI: 10.1007/s1054901536355. ［15］ Gevensleben H, GarciaMurillas I, Graeser MK, et al. Noninvasive detection of HER2 amplification with plasma DNA digital PCR［J］. Clin Cancer Res, 2013, 19(12): 32763284. DOI: 10.1158/10780432.CCR123768. ［16］ Sefrioui D, Perdrix A, SarafanVasseur N, et al. Short report: monitoring ESR1 mutations by circulating tumor DNA in aromatase inhibitor resistant metastatic breast cancer［J］. Int J Cancer, 2015, 137(10): 25132519. DOI: 10.1002/ijc.29612. ［17］ Madic J, Kiialainen A, Bidard FC, et al. Circulating tumor DNA and circulating tumor cells in metastatic triple negative breast cancer patients［J］. Int J Cancer, 2015, 136(9): 21582165. DOI: 10.1002/ijc.29265. ［18］ Board RE, Wardley AM, Dixon JM, et al. Detection of PIK3CA mutations in circulating free DNA in patients with breast cancer［J］. Breast Cancer Res Treat, 2010, 120(2): 461467. DOI: 10.1007/s1054901007479. ［19］ Higgins MJ, Jelovac D, Barnathan E, et al. Detection of tumor PIK3CA status in metastatic breast cancer using peripheral blood［J］. Clin Cancer Res, 2012, 18(12): 34623469. DOI: 10.1158/10780432.CCR112696. ［20］ Murtaza M, Dawson SJ, Tsui DW, et al. Noninvasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA［J］. Nature, 2013, 497(7447): 108112. DOI: 10.1038/nature12065. ［21］ Tryfonidis K, Zardavas D, Katzenellenbogen BS, et al. Endocrine treatment in breast cancer: cure, resistance and beyond［J］. Cancer Treat Rev, 2016, 50: 6881. DOI: 10.1016/j.ctrv.2016.08.008. ［22］ Spoerke JM, Gendreau S, Walter K, et al. Heterogeneity and clinical significance of ESR1 mutations in ERpositive metastatic breast cancer patients receiving fulvestrant［J］. Nat Commun, 2016, 7: 11579. DOI: 10.1038/ncomms11579. ［23］ Wang P, Bahreini A, Gyanchandani R, et al. Sensitive detection of mono and polyclonal ESR1 mutations in primary tumors, metastatic lesions, and cellfree DNA of breast cancer patients［J］. Clin Cancer Res, 2016, 22(5): 11301137. DOI: 10.1158/10780432.CCR151534. ［24］ 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［J］. Sci Transl Med, 2015, 7(313): 313ra182. DOI: 10.1126/scitranslmed.aac7551. ［25］ Miller TW, Rexer BN, Garrett JT, et al. Mutations in the phosphatidylinositol 3kinase pathway: role in tumor progression and therapeutic implications in breast cancer［J］. Breast Cancer Res, 2011, 13(6): 224. DOI: 10.1186/bcr3039. ［26］ Oshiro C, Kagara N, Naoi Y, et al. PIK3CA mutations in serum DNA are predictive of recurrence in primary breast cancer patients［J］. Breast Cancer Res Treat, 2015, 150(2): 299307. DOI: 10.1007/s1054901533226. ［27］ 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［J］. Cancer Sci, 2015, 106(11): 15821589. DOI: 10.1111/cas.12813. ［28］ Gu G, Fuqua SA. ESR1 mutations in breast cancer: proofofconcept challenges clinical action［J］. Clin Cancer Res, 2016, 22(5): 10341036. DOI: 10.1158/10780432.CCR152549. ［29］ Beaver JA, Park BH. The BOLERO2 trial: the addition of everolimus to exemestane in the treatment of postmenopausal hormone receptorpositive advanced breast cancer［J］. Future Oncol, 2012, 8(6): 651657. DOI: 10.2217/fon.12.49. ［30］ Arnedos M, Vicier C, Loi S, et al. Precision medicine for metastatic breast cancerlimitations and solutions［J］. Nat Rev Clin Oncol, 2015, 12(12): 693704. DOI: 10.1038/nrclinonc.2015.123.

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