依维莫司联合氟维司群用于激素受体阳性晚期乳腺癌的研究进展
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摘要
乳腺癌是一种经典的激素依赖性肿瘤,内分泌治疗是激素受体阳性[HR(+)]/人表皮生长因子2阴性[HER-2(-)]晚期乳腺癌的主要治疗方法。传统的内分泌药物,如他莫昔芬、芳香化酶抑制剂(AI)和氟维司群已被广泛应用于晚期(局部晚期或转移)绝经后患者。然而,对于这种亚型的乳腺癌患者,在引入靶向药物,如人哺乳动物雷帕霉素位点(mTOR)抑制剂和细胞周期蛋白依赖性激酶4/6(CDK4/6)抑制剂后,内分泌治疗的选择已经扩大,出现了各种靶向药物与内分泌治疗的组合。本文旨在探讨m TOR抑制剂依维莫司联合氟维司群在对AI耐药的雌激素受体阳性[ER(+)]/HER-2(-)晚期乳腺癌中的应用。
Breast cancer is a classic hormone-dependent tumor, so endocrine therapy is a major treatment for hormonereceptor-positive [HR(+)],human-epidermal-growth-factor-2-negative [HER-2(-)] and advanced breast cancer.Traditional endocrine drugs, such as tamoxifen, aromatase inhibitors(AI) and fulvestrant, have been widely used in advanced(locally advanced or metastatic) postmenopausal patients. However, for this subtype of breast cancer patients, after the appearance of targeted drug, such as mammalian target of rapamycin(mTOR) inhibitors and cyclin-dependent kinases 4 and6(CDK4/6) inhibitors, the choice of endocrine therapy has been expanded. There has been various combination of targeted drugs and endocrine therapy. This article aims to explore the application of mTOR inhibitor everolimus combined with fulvestrant in the treatment of AI-resistant estrogen-receptor-positive [ER(+)]/HER-2(-) advanced breast cancer.
Breast cancer is a classic hormone-dependent tumor, so endocrine therapy is a major treatment for hormonereceptor-positive [HR(+)],human-epidermal-growth-factor-2-negative [HER-2(-)] and advanced breast cancer.Traditional endocrine drugs, such as tamoxifen, aromatase inhibitors(AI) and fulvestrant, have been widely used in advanced(locally advanced or metastatic) postmenopausal patients. However, for this subtype of breast cancer patients, after the appearance of targeted drug, such as mammalian target of rapamycin(mTOR) inhibitors and cyclin-dependent kinases 4 and6(CDK4/6) inhibitors, the choice of endocrine therapy has been expanded. There has been various combination of targeted drugs and endocrine therapy. This article aims to explore the application of mTOR inhibitor everolimus combined with fulvestrant in the treatment of AI-resistant estrogen-receptor-positive [ER(+)]/HER-2(-) advanced breast cancer.
引文
[1]夏雯,王树森.激素受体阳性乳腺癌靶向治疗进展[J].中国肿瘤临床,2017,44(13):635-639. Xia W,Wang SS. Advances oftarget therapy in hormone-receptor-positive breast cancer[J]. ChinJ Clin Oncol,2017,44(13):635-639. doi:10.3969/j.issn.1000-8179.2017.13.008.
[2] Perez EA. Treatment strategies for advanced hormone receptor-positive and human epidermal growth factor 2-negative breastcancer:the role of treatment order[J]. Drug Resist Updat,2016,24:13-22. doi:10.1016/j.drup.2015.11.001.
[3] Reinert T,de Paula B,Shafaee MN,et al. Endocrine therapy forER-positive/HER2-negative metastatic breast cancer[J]. ChinClin Oncol,2018,7(3):25. doi:10.21037/cco.2018.06.06.
[4] Lee CI,Goodwin A,Wilcken N. Fulvestrant for hormone-sensitivemetastatic breast cancer[J]. Cochrane Database Syst Rev,2017,1:D11093. doi:10.1002/14651858.CD011093.pub2.
[5] Boer K. Fulvestrant in advanced breast cancer:evidence to dateand place in therapy[J]. Ther Adv Med Oncol,2017,9(7):465-479. doi:10.1177/1758834017711097.
[6] Blancas I,Fontanillas M,Conde V,et al. Efficacy of fulvestrant inthe treatment of postmenopausal women with endocrine-resistantadvanced breast cancer in routine clinical practice[J]. Clin TranslOncol,2018,20(7):862-869. doi:10.1007/s12094-017-1797-9.
[7] Di Leo A,Jerusalem G,Petruzelka L,et al. Final overall survival:fulvestrant 500 mg vs 250 mg in the randomized CONFIRM trial[J]. J Natl Cancer Inst,2014,106(1):djt337. doi:10.1093/jnci/djt337.
[8] Pizzuti L,Natoli C,Gamucci T,et al. Anthropometric,clinical andmolecular determinants of treatment outcomes in postmenopausal,hormone receptor positive metastatic breast cancer patients treatedwith fulvestrant:Results from a real word setting[J]. Oncotarget,2017,8(40):69025-69037. doi:10.18632/oncotarget.16982.
[9]徐晓芸.氟维司群治疗受体阳性的晚期绝经后乳腺癌不良反应的观察及护理[J].江苏医药,2014,40(23):2959-2960. Xu XY.Observation and nursing of adverse drug reactions of latepostmenopausal breast cancer treated with fulvestrant[J]. JiangsuMed J,2014,40(23):2959-2960. doi:10.19460/j. cnki. 0253-3685.2014.23.070.
[10]Moes DJ, Press RR, den Hartigh J, et al. Populationpharmacokinetics and pharmacogenetics of everolimus in renaltransplant patients[J]. Clin Pharmacokinet,2012,51(7):467-480.doi:10.2165/11599710-000000000-00000.
[11]Paplomata E,O′Regan R. The PI3K/AKT/mTOR pathway in breastcancer:targets,trials and biomarkers[J]. Ther Adv Med Oncol,2014,6(4):154-166. doi:10.1177/1758834014530023.
[12]Yi Z,Ma F. Biomarkers of everolimus sensitivity in hormonereceptor-positive breast cancer[J]. J Breast Cancer,2017,20(4):321-326. doi:10.4048/jbc.2017.20.4.321.
[13]Lousberg L,Jerusalem G. Safety,efficacy,and patient acceptabilityof everolimus in the treatment of breast cancer[J]. Breast Cancer(Auckl),2017,10:239-252. doi:10.4137/BCBCR.S12443.
[14]Citi V,Del RM,Martelli A,et al. Phosphorylation of AKT andERK1/2 and mutations of PIK3CA and PTEN are predictive ofbreast cancer cell sensitivity to everolimus in vitro[J]. CancerChemother Pharmacol,2018,81(4):745-754. doi:10.1007/s00280-018-3543-6.
[15]Wood R,Mitra D,de Courcy J,et al. Patient-reported quality of lifeand treatment satisfaction in patients with HR(+)/HER2(-)advanced/metastatic breast cancer[J]. Clin Ther,2017,39(8):1719-1728. doi:10.1016/j.clinthera.2017.07.009.
[16]Dalmau E,Armengol-Alonso A,Munoz M,et al. Current status ofhormone therapy in patients with hormone receptor positive(HR+)advanced breast cancer[J]. Breast,2014,23(6):710-720. doi:10.1016/j.breast.2014.09.006.
[17]Strasser-Weippl K,Goss PE. Advances in adjuvant hormonaltherapy for postmenopausal women[J]. J Clin Oncol,2005,23(8):1751-1759.
[18]Hole S,Pedersen AM,Hansen SK,et al. New cell culture model foraromatase inhibitor-resistant breast cancer shows sensitivity tofulvestrant treatment and cross-resistance between letrozole andexemestane[J]. Int J Oncol,2015,46(4):1481-1490. doi:10.3892/ijo.2015.2850.
[19]O′Donovan N,Byrne AT,O′Connor AE,et al. Synergisticinteraction between trastuzumab and EGFR/HER-2 tyrosine kinaseinhibitors in HER-2 positive breast cancer cells[J]. Invest NewDrugs,2011,29(5):752-759. doi:10.1007/s10637-010-9415-5.
[20]Arpino G,De Angelis C,Giuliano M,et al. Molecular mechanismand clinical implications of endocrine therapy resistance in breastcancer[J]. Oncology,2009,77 Suppl 1:23-37. doi:10.1159/000258493.
[21]Pernas S,Tolaney SM,Winer EP,et al. CDK4/6 inhibition in breastcancer:current practice and future directions[J]. Ther Adv MedOncol,2018,10:433565805. doi:10.1177/1758835918786451.
[22]Gourdy P,Guillaume M,Fontaine C,et al. Estrogen receptorsubcellular localization and cardiometabolism[J]. Mol Metab,2018,15:56-69. doi:10.1016/j.molmet.2018.05.009.
[23]Lim E,Winer EP. Adjuvant chemotherapy in luminal breast cancers[J]. Breast,2011,20(Suppl 3):S128-S131. doi:10.1016/S0960-9776(11)70309-5.
[24]Prat A,Pineda E,Adamo B,et al. Clinical implications of theintrinsic molecular subtypes of breast cancer[J]. Breast,2015,24Suppl 2:S26-S35. doi:10.1016/j.breast.2015.07.008.
[25]Finn RS,Press MF,Dering J,et al. Quantitative ER and PgRassessment as predictors of benefit from lapatinib inpostmenopausal women with hormone receptor-positive,HER2-negative metastatic breast cancer[J]. Clin Cancer Res,2014,20(3):736-743. doi:10.1158/1078-0432.CCR-13-1260.
[26]Zucchini G,Armstrong AC,Wardley AM,et al. A phase II trial oflow-dose estradiol in postmenopausal women with advanced breastcancer and acquired resistance to aromatase inhibition[J]. Eur JCancer,2015,51(18):2725-2731. doi:10.1016/j.ejca.2015.08.028.
[27]Iyengar A,Sheppard D. A case of erythrocytosis in a patient treatedwith an aromatase inhibitor for breast cancer[J]. Case RepHematol,2013,2013:615189. doi:10.1155/2013/615189.
[28]Poorolajal J,Nafissi N,Akbari ME,et al. Breast cancer survivalanalysis based on immunohistochemistry subtypes(ER/PR/HER2):a retrospective cohort study[J]. Arch Iran Med,2016,19(10):680-686. doi:0161910/AIM.003.
[29]Yan C,Wei H,Minjuan Z,et al. The mTOR inhibitor rapamycinsynergizes with a fatty acid synthase inhibitor to induce cytotoxicity in ER/HER2-positive breast cancer cells[J]. PLoS One,2014,9(5):e97697. doi:10.1371/journal.pone.0097697.
[30]Wheler JJ,Moulder SL,Naing A,et al. Anastrozole and everolimusin advanced gynecologic and breast malignancies:activity andmolecular alterations in the PI3K/AKT/mTOR pathway[J].Oncotarget, 2014, 5(10):3029-3038. doi:10.18632/oncotarget.1799.
[31]Massihnia D,Galvano A,Fanale D,et al. Triple negative breastcancer:shedding light onto the role of pi3k/akt/mtor pathway[J].Oncotarget,2016,7(37):60712-60722. doi:10.18632/oncotarget.10858.
[32]Nordenskjold A,Fohlin H,Fornander T,et al. Progesteronereceptor positivity is a predictor of long-term benefit from adjuvanttamoxifen treatment of estrogen receptor positive breast cancer[J].Breast Cancer Res Treat,2016,160(2):313-322. doi:10.1007/s10549-016-4007-5.
[33]Yu P,Zhang Z,Li S,et al. Progesterone modulates endothelialprogenitor cell(EPC)viability through the CXCL12/CXCR4/PI3K/Akt signalling pathway[J]. Cell Prolif,2016,49(1):48-57. doi:10.1111/cpr.12231.
[34]Kim J,Lee J,Kim C,et al. Anti-cancer effect of metformin bysuppressing signaling pathway of HER2 and HER3 in tamoxifen-resistant breast cancer cells[J]. Tumour Biol,2016,37(5):5811-5819. doi:10.1007/s13277-015-4440-9.
[35]Sun L,Yu DH,Sun SY,et al. Expressions of ER,PR,HER-2,COX-2,and VEGF in primary and relapsed/metastatic breastcancers[J]. Cell Biochem Biophys,2014,68(3):511-516. doi:10.1007/s12013-013-9729-y.
[36]James R,Thriveni K,Krishnamoorthy L,et al. Clinical outcome ofadjuvant endocrine treatment according to Her-2/neu status inbreast cancer[J]. Indian J Med Res,2011,133:70-75.
[37]Fan W,Chang J,Fu P. Endocrine therapy resistance in breastcancer:current status,possible mechanisms and overcomingstrategies[J]. Future Med Chem,2015,7(12):1511-1519. doi:10.4155/fmc.15.93.
[38]Fan J,Yin WJ,Lu JS,et al. ER alpha negative breast cancer cellsrestore response to endocrine therapy by combination treatmentwith both HDAC inhibitor and DNMT inhibitor[J]. J Cancer ResClin Oncol,2008,134(8):883-890. doi:10.1007/s00432-008-0354-x.
[39]Martin LA,Ribas R,Simigdala N,et al. Discovery of naturallyoccurring ESR1 mutations in breast cancer cell lines modellingendocrine resistance[J]. Nat Commun,2017,8(1):1865. doi:10.1038/s41467-017-01864-y.
[40]Fribbens C,O′Leary B,Kilburn L,et al. Plasma ESR1 mutationsand the treatment of estrogen receptor-positive advanced breastcancer[J]. J Clin Oncol,2016,34(25):2961-2968. doi:10.1200/JCO.2016.67.3061.
[41]Ladd B,Mazzola AM,Bihani T,et al. Effective combinationtherapies in preclinical endocrine resistant breast cancer modelsharboring ER mutations[J]. Oncotarget,2016,7(34):54120-54136. doi:10.18632/oncotarget.10852.
[42]Yardley DA,Noguchi S,Pritchard KI,et al. Everolimus plusexemestane in postmenopausal patients with HR(+)breast cancer:BOLERO-2 final progression-free survival analysis[J]. Adv Ther,2013,30(10):870-884. doi:10.1007/s12325-013-0060-1.
[43]Bachelot T,Bourgier C,Cropet C,et al. Randomized phase II trialof everolimus in combination with tamoxifen in patients withhormone receptor-positive,human epidermal growth factor receptor2-negative metastatic breast cancer with prior exposure toaromatase inhibitors:a GINECO study[J]. J Clin Oncol,2012,30(22):2718-2724. doi:10.1200/JCO.2011.39.0708.
[44]Hao Y,Lin PL,Xie J,et al. Real-world effectiveness of everolimus-based therapy versus fulvestrant monotherapy in HR(+)/HER2(-)metastatic breast cancer[J]. J Comp Eff Res,2015,4(4):315-326.doi:10.2217/cer.15.25.
[45]Muller V,Gluz O,Pierga JY,et al. San Antonio 2016:Progress onthe long way to individualized treatment of breast cancer[J]. BreastCare(Basel),2017,12(1):54-58. doi:10.1159/000458749.
[46]Everolimus boosts endocrine therapy for breast cancer[J]. CancerDiscov,2017,7(2):OF1. doi:10.1158/2159-8290. CD-NB2016-162.
[47]Massarweh S,Romond E,Black EP,et al. A phase II study ofcombined fulvestrant and everolimus in patients with metastaticestrogen receptor(ER)-positive breast cancer after aromataseinhibitor(AI)failure[J]. Breast Cancer Res Treat,2014,143(2):325-332. doi:10.1007/s10549-013-2810-9.
[48]Ladd B,Mazzola AM,Bihani T,et al. Effective combinationtherapies in preclinical endocrine resistant breast cancer modelsharboring ER mutations[J]. Oncotarget,2016,7(34):54120-54136. doi:10.18632/oncotarget.10852.
[49]Sun B,Ding L,Wu S,et al. Combined treatment with everolimusand fulvestrant reversed anti-HER2 resistance in a patient withrefractory advanced breast cancer:a case report[J]. Onco TargetsTher,2016,9:3997-4003. doi:10.2147/OTT.S104398.
[50]Bachelot T,Bourgier C,Cropet C,et al. Randomized phase II trialof everolimus in combination with tamoxifen in patients withhormone receptor-positive,human epidermal growth factor receptor2-negative metastatic breast cancer with prior exposure toaromatase inhibitors:a GINECO study[J]. J Clin Oncol,2012,30(22):2718-2724. doi:10.1200/JCO.2011.39.0708.
[51]Massarweh S,Romond E,Black EP,et al. A phase II study ofcombined fulvestrant and everolimus in patients with metastaticestrogen receptor(ER)-positive breast cancer after aromataseinhibitor(AI)failure[J]. Breast Cancer Res Treat,2014,143(2):325-332. doi:10.1007/s10549-013-2810-9.
[52]Polanyi Z,Dale P,Taylor M,et al. Everolimus plus exemestanecompared to exemestane and fulvestrant for the treatment of ER+HER2-metastastic breast cancer in the United Kingdom-asocietal perspective[J]. Value Health,2014,17(7):A632. doi:10.1016/j.jval.2014.08.2262.
[2] Perez EA. Treatment strategies for advanced hormone receptor-positive and human epidermal growth factor 2-negative breastcancer:the role of treatment order[J]. Drug Resist Updat,2016,24:13-22. doi:10.1016/j.drup.2015.11.001.
[3] Reinert T,de Paula B,Shafaee MN,et al. Endocrine therapy forER-positive/HER2-negative metastatic breast cancer[J]. ChinClin Oncol,2018,7(3):25. doi:10.21037/cco.2018.06.06.
[4] Lee CI,Goodwin A,Wilcken N. Fulvestrant for hormone-sensitivemetastatic breast cancer[J]. Cochrane Database Syst Rev,2017,1:D11093. doi:10.1002/14651858.CD011093.pub2.
[5] Boer K. Fulvestrant in advanced breast cancer:evidence to dateand place in therapy[J]. Ther Adv Med Oncol,2017,9(7):465-479. doi:10.1177/1758834017711097.
[6] Blancas I,Fontanillas M,Conde V,et al. Efficacy of fulvestrant inthe treatment of postmenopausal women with endocrine-resistantadvanced breast cancer in routine clinical practice[J]. Clin TranslOncol,2018,20(7):862-869. doi:10.1007/s12094-017-1797-9.
[7] Di Leo A,Jerusalem G,Petruzelka L,et al. Final overall survival:fulvestrant 500 mg vs 250 mg in the randomized CONFIRM trial[J]. J Natl Cancer Inst,2014,106(1):djt337. doi:10.1093/jnci/djt337.
[8] Pizzuti L,Natoli C,Gamucci T,et al. Anthropometric,clinical andmolecular determinants of treatment outcomes in postmenopausal,hormone receptor positive metastatic breast cancer patients treatedwith fulvestrant:Results from a real word setting[J]. Oncotarget,2017,8(40):69025-69037. doi:10.18632/oncotarget.16982.
[9]徐晓芸.氟维司群治疗受体阳性的晚期绝经后乳腺癌不良反应的观察及护理[J].江苏医药,2014,40(23):2959-2960. Xu XY.Observation and nursing of adverse drug reactions of latepostmenopausal breast cancer treated with fulvestrant[J]. JiangsuMed J,2014,40(23):2959-2960. doi:10.19460/j. cnki. 0253-3685.2014.23.070.
[10]Moes DJ, Press RR, den Hartigh J, et al. Populationpharmacokinetics and pharmacogenetics of everolimus in renaltransplant patients[J]. Clin Pharmacokinet,2012,51(7):467-480.doi:10.2165/11599710-000000000-00000.
[11]Paplomata E,O′Regan R. The PI3K/AKT/mTOR pathway in breastcancer:targets,trials and biomarkers[J]. Ther Adv Med Oncol,2014,6(4):154-166. doi:10.1177/1758834014530023.
[12]Yi Z,Ma F. Biomarkers of everolimus sensitivity in hormonereceptor-positive breast cancer[J]. J Breast Cancer,2017,20(4):321-326. doi:10.4048/jbc.2017.20.4.321.
[13]Lousberg L,Jerusalem G. Safety,efficacy,and patient acceptabilityof everolimus in the treatment of breast cancer[J]. Breast Cancer(Auckl),2017,10:239-252. doi:10.4137/BCBCR.S12443.
[14]Citi V,Del RM,Martelli A,et al. Phosphorylation of AKT andERK1/2 and mutations of PIK3CA and PTEN are predictive ofbreast cancer cell sensitivity to everolimus in vitro[J]. CancerChemother Pharmacol,2018,81(4):745-754. doi:10.1007/s00280-018-3543-6.
[15]Wood R,Mitra D,de Courcy J,et al. Patient-reported quality of lifeand treatment satisfaction in patients with HR(+)/HER2(-)advanced/metastatic breast cancer[J]. Clin Ther,2017,39(8):1719-1728. doi:10.1016/j.clinthera.2017.07.009.
[16]Dalmau E,Armengol-Alonso A,Munoz M,et al. Current status ofhormone therapy in patients with hormone receptor positive(HR+)advanced breast cancer[J]. Breast,2014,23(6):710-720. doi:10.1016/j.breast.2014.09.006.
[17]Strasser-Weippl K,Goss PE. Advances in adjuvant hormonaltherapy for postmenopausal women[J]. J Clin Oncol,2005,23(8):1751-1759.
[18]Hole S,Pedersen AM,Hansen SK,et al. New cell culture model foraromatase inhibitor-resistant breast cancer shows sensitivity tofulvestrant treatment and cross-resistance between letrozole andexemestane[J]. Int J Oncol,2015,46(4):1481-1490. doi:10.3892/ijo.2015.2850.
[19]O′Donovan N,Byrne AT,O′Connor AE,et al. Synergisticinteraction between trastuzumab and EGFR/HER-2 tyrosine kinaseinhibitors in HER-2 positive breast cancer cells[J]. Invest NewDrugs,2011,29(5):752-759. doi:10.1007/s10637-010-9415-5.
[20]Arpino G,De Angelis C,Giuliano M,et al. Molecular mechanismand clinical implications of endocrine therapy resistance in breastcancer[J]. Oncology,2009,77 Suppl 1:23-37. doi:10.1159/000258493.
[21]Pernas S,Tolaney SM,Winer EP,et al. CDK4/6 inhibition in breastcancer:current practice and future directions[J]. Ther Adv MedOncol,2018,10:433565805. doi:10.1177/1758835918786451.
[22]Gourdy P,Guillaume M,Fontaine C,et al. Estrogen receptorsubcellular localization and cardiometabolism[J]. Mol Metab,2018,15:56-69. doi:10.1016/j.molmet.2018.05.009.
[23]Lim E,Winer EP. Adjuvant chemotherapy in luminal breast cancers[J]. Breast,2011,20(Suppl 3):S128-S131. doi:10.1016/S0960-9776(11)70309-5.
[24]Prat A,Pineda E,Adamo B,et al. Clinical implications of theintrinsic molecular subtypes of breast cancer[J]. Breast,2015,24Suppl 2:S26-S35. doi:10.1016/j.breast.2015.07.008.
[25]Finn RS,Press MF,Dering J,et al. Quantitative ER and PgRassessment as predictors of benefit from lapatinib inpostmenopausal women with hormone receptor-positive,HER2-negative metastatic breast cancer[J]. Clin Cancer Res,2014,20(3):736-743. doi:10.1158/1078-0432.CCR-13-1260.
[26]Zucchini G,Armstrong AC,Wardley AM,et al. A phase II trial oflow-dose estradiol in postmenopausal women with advanced breastcancer and acquired resistance to aromatase inhibition[J]. Eur JCancer,2015,51(18):2725-2731. doi:10.1016/j.ejca.2015.08.028.
[27]Iyengar A,Sheppard D. A case of erythrocytosis in a patient treatedwith an aromatase inhibitor for breast cancer[J]. Case RepHematol,2013,2013:615189. doi:10.1155/2013/615189.
[28]Poorolajal J,Nafissi N,Akbari ME,et al. Breast cancer survivalanalysis based on immunohistochemistry subtypes(ER/PR/HER2):a retrospective cohort study[J]. Arch Iran Med,2016,19(10):680-686. doi:0161910/AIM.003.
[29]Yan C,Wei H,Minjuan Z,et al. The mTOR inhibitor rapamycinsynergizes with a fatty acid synthase inhibitor to induce cytotoxicity in ER/HER2-positive breast cancer cells[J]. PLoS One,2014,9(5):e97697. doi:10.1371/journal.pone.0097697.
[30]Wheler JJ,Moulder SL,Naing A,et al. Anastrozole and everolimusin advanced gynecologic and breast malignancies:activity andmolecular alterations in the PI3K/AKT/mTOR pathway[J].Oncotarget, 2014, 5(10):3029-3038. doi:10.18632/oncotarget.1799.
[31]Massihnia D,Galvano A,Fanale D,et al. Triple negative breastcancer:shedding light onto the role of pi3k/akt/mtor pathway[J].Oncotarget,2016,7(37):60712-60722. doi:10.18632/oncotarget.10858.
[32]Nordenskjold A,Fohlin H,Fornander T,et al. Progesteronereceptor positivity is a predictor of long-term benefit from adjuvanttamoxifen treatment of estrogen receptor positive breast cancer[J].Breast Cancer Res Treat,2016,160(2):313-322. doi:10.1007/s10549-016-4007-5.
[33]Yu P,Zhang Z,Li S,et al. Progesterone modulates endothelialprogenitor cell(EPC)viability through the CXCL12/CXCR4/PI3K/Akt signalling pathway[J]. Cell Prolif,2016,49(1):48-57. doi:10.1111/cpr.12231.
[34]Kim J,Lee J,Kim C,et al. Anti-cancer effect of metformin bysuppressing signaling pathway of HER2 and HER3 in tamoxifen-resistant breast cancer cells[J]. Tumour Biol,2016,37(5):5811-5819. doi:10.1007/s13277-015-4440-9.
[35]Sun L,Yu DH,Sun SY,et al. Expressions of ER,PR,HER-2,COX-2,and VEGF in primary and relapsed/metastatic breastcancers[J]. Cell Biochem Biophys,2014,68(3):511-516. doi:10.1007/s12013-013-9729-y.
[36]James R,Thriveni K,Krishnamoorthy L,et al. Clinical outcome ofadjuvant endocrine treatment according to Her-2/neu status inbreast cancer[J]. Indian J Med Res,2011,133:70-75.
[37]Fan W,Chang J,Fu P. Endocrine therapy resistance in breastcancer:current status,possible mechanisms and overcomingstrategies[J]. Future Med Chem,2015,7(12):1511-1519. doi:10.4155/fmc.15.93.
[38]Fan J,Yin WJ,Lu JS,et al. ER alpha negative breast cancer cellsrestore response to endocrine therapy by combination treatmentwith both HDAC inhibitor and DNMT inhibitor[J]. J Cancer ResClin Oncol,2008,134(8):883-890. doi:10.1007/s00432-008-0354-x.
[39]Martin LA,Ribas R,Simigdala N,et al. Discovery of naturallyoccurring ESR1 mutations in breast cancer cell lines modellingendocrine resistance[J]. Nat Commun,2017,8(1):1865. doi:10.1038/s41467-017-01864-y.
[40]Fribbens C,O′Leary B,Kilburn L,et al. Plasma ESR1 mutationsand the treatment of estrogen receptor-positive advanced breastcancer[J]. J Clin Oncol,2016,34(25):2961-2968. doi:10.1200/JCO.2016.67.3061.
[41]Ladd B,Mazzola AM,Bihani T,et al. Effective combinationtherapies in preclinical endocrine resistant breast cancer modelsharboring ER mutations[J]. Oncotarget,2016,7(34):54120-54136. doi:10.18632/oncotarget.10852.
[42]Yardley DA,Noguchi S,Pritchard KI,et al. Everolimus plusexemestane in postmenopausal patients with HR(+)breast cancer:BOLERO-2 final progression-free survival analysis[J]. Adv Ther,2013,30(10):870-884. doi:10.1007/s12325-013-0060-1.
[43]Bachelot T,Bourgier C,Cropet C,et al. Randomized phase II trialof everolimus in combination with tamoxifen in patients withhormone receptor-positive,human epidermal growth factor receptor2-negative metastatic breast cancer with prior exposure toaromatase inhibitors:a GINECO study[J]. J Clin Oncol,2012,30(22):2718-2724. doi:10.1200/JCO.2011.39.0708.
[44]Hao Y,Lin PL,Xie J,et al. Real-world effectiveness of everolimus-based therapy versus fulvestrant monotherapy in HR(+)/HER2(-)metastatic breast cancer[J]. J Comp Eff Res,2015,4(4):315-326.doi:10.2217/cer.15.25.
[45]Muller V,Gluz O,Pierga JY,et al. San Antonio 2016:Progress onthe long way to individualized treatment of breast cancer[J]. BreastCare(Basel),2017,12(1):54-58. doi:10.1159/000458749.
[46]Everolimus boosts endocrine therapy for breast cancer[J]. CancerDiscov,2017,7(2):OF1. doi:10.1158/2159-8290. CD-NB2016-162.
[47]Massarweh S,Romond E,Black EP,et al. A phase II study ofcombined fulvestrant and everolimus in patients with metastaticestrogen receptor(ER)-positive breast cancer after aromataseinhibitor(AI)failure[J]. Breast Cancer Res Treat,2014,143(2):325-332. doi:10.1007/s10549-013-2810-9.
[48]Ladd B,Mazzola AM,Bihani T,et al. Effective combinationtherapies in preclinical endocrine resistant breast cancer modelsharboring ER mutations[J]. Oncotarget,2016,7(34):54120-54136. doi:10.18632/oncotarget.10852.
[49]Sun B,Ding L,Wu S,et al. Combined treatment with everolimusand fulvestrant reversed anti-HER2 resistance in a patient withrefractory advanced breast cancer:a case report[J]. Onco TargetsTher,2016,9:3997-4003. doi:10.2147/OTT.S104398.
[50]Bachelot T,Bourgier C,Cropet C,et al. Randomized phase II trialof everolimus in combination with tamoxifen in patients withhormone receptor-positive,human epidermal growth factor receptor2-negative metastatic breast cancer with prior exposure toaromatase inhibitors:a GINECO study[J]. J Clin Oncol,2012,30(22):2718-2724. doi:10.1200/JCO.2011.39.0708.
[51]Massarweh S,Romond E,Black EP,et al. A phase II study ofcombined fulvestrant and everolimus in patients with metastaticestrogen receptor(ER)-positive breast cancer after aromataseinhibitor(AI)failure[J]. Breast Cancer Res Treat,2014,143(2):325-332. doi:10.1007/s10549-013-2810-9.
[52]Polanyi Z,Dale P,Taylor M,et al. Everolimus plus exemestanecompared to exemestane and fulvestrant for the treatment of ER+HER2-metastastic breast cancer in the United Kingdom-asocietal perspective[J]. Value Health,2014,17(7):A632. doi:10.1016/j.jval.2014.08.2262.