Insulin-like growth factor-1 receptor (IGF-1R) expression on circulating tumor cells (CTCs) and metastatic breast cancer outcome: results from the TransMYME trial.
Aged
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Biomarkers, Tumor
/ metabolism
Breast Neoplasms
/ blood
Clinical Trials, Phase II as Topic
Female
Follow-Up Studies
Humans
Middle Aged
Neoplasm Metastasis
Neoplastic Cells, Circulating
/ metabolism
Prognosis
Prospective Studies
Randomized Controlled Trials as Topic
Receptor, IGF Type 1
/ metabolism
Survival Rate
Treatment Outcome
Breast cancer (BC)
Circulating tumor cells (CTCs)
Clinical trials
Invasion
Liquid biopsy
Metastasis
Journal
Breast cancer research and treatment
ISSN: 1573-7217
Titre abrégé: Breast Cancer Res Treat
Pays: Netherlands
ID NLM: 8111104
Informations de publication
Date de publication:
May 2020
May 2020
Historique:
received:
30
10
2019
accepted:
12
03
2020
pubmed:
23
3
2020
medline:
9
1
2021
entrez:
23
3
2020
Statut:
ppublish
Résumé
To evaluate the prognostic value of IGF-1R expression on circulating tumor cells (CTCs) in a prospective randomized clinical trial comparing chemotherapy plus metformin with chemotherapy alone in metastatic breast cancer (MBC) patients. CTCs were collected at baseline and at the end of chemotherapy. An automated sample preparation and analysis system (CellSearch) were customized for detecting IGF-1R expression. The prognostic role of CTC count and IGF-1R was assessed for PFS and OS by univariate and multivariate analyses. Seventy-two out of 126 randomized patients were evaluated: 57% had ≥ 1 IGF-1R positive CTC and 37.5% ≥ 4 IGF-1R negative cells; 42% had CTC count ≥ 5/7.5 ml. At univariate analysis, the number of IGF-1R negative CTCs was strongly associated with risk of progression and death: HR 1.93 (P = 0.013) and 3.65 (P = 0.001), respectively; no association was detected between number of IGF-1R positive CTCs and PFS or OS (P = 0.322 and P = 0.840). The prognostic role of CTC count was confirmed: HR 1.69, P = 0.042 for PFS and HR 2.80 for OS, P = 0.002. By multivariate analysis, the prognostic role of the number of IGF-1R negative CTCs was maintained, while no residual prognostic role of CTC count or number of IGF-1R positive cells was found. Loss of IGF-1R in CTCs is associated with a significantly worse outcome in MBC patients. This finding supports further evaluation for the role of IGF-1R on CTCs to improve patient stratification and to implement new targeted strategies. Clinicaltrials.gov (NCT01885013); European Clinical Trials Database (EudraCT No.2009-014,662-26).
Identifiants
pubmed: 32200486
doi: 10.1007/s10549-020-05596-4
pii: 10.1007/s10549-020-05596-4
doi:
Substances chimiques
Biomarkers, Tumor
0
IGF1R protein, human
0
Receptor, IGF Type 1
EC 2.7.10.1
Banques de données
ClinicalTrials.gov
['NCT01885013']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
61-68Subventions
Organisme : Associazione Italiana per la Ricerca sul Cancro
ID : 9232
Références
Pollak M (2008) Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer 8:915–928. https://doi.org/10.1038/nrc2536
doi: 10.1038/nrc2536
pubmed: 19029956
Pollak MN, Schernhammer ES, Hankinson SE (2004) Insulin-like growth factors and neoplasia. Nat Rev Cancer 4:505–518. https://doi.org/10.1038/nrc1387
doi: 10.1038/nrc1387
pubmed: 15229476
Pollak MN, Chapman JW, Pritchard KI, Krook JE, Dhaliwal HS, Vandenberg TA et al (2006) Insulin resistance, estimated by serum c-peptide level, is associated with reduced event-free survival for postmenopausal women in the NCIC MA14 adjuvant BC trial. J Clin Oncol 24(Suppl):524. https://doi.org/10.1200/jco.2006.24.18_suppl.524
doi: 10.1200/jco.2006.24.18_suppl.524
Goodwin PJ, Ennis M, Pritchard KI, Trudeau ME, Koo J, Madarnas Y et al (2002) Fasting insulin and outcome in early-stage BC: results of a prospective cohort study. J Clin Oncol 20:42–51. https://doi.org/10.1200/JCO.2002.20.1.42
doi: 10.1200/JCO.2002.20.1.42
pubmed: 11773152
Sandhu MS, Dunger DB, Giovannucci EL (2022) Insulin, insulin-like growth factor-I (IGF-I), IGF binding proteins, their biologic interactions, and colorectal cancer. J Natl Cancer Inst 94:972–980. https://doi.org/10.1093/jnci/94.13.972
doi: 10.1093/jnci/94.13.972
Sachdev D, Yee D (2007) Disrupting insulin-like growth factor signaling as a potential cancer therapy. Mol Cancer Ther 6:1–12. https://doi.org/10.1158/1535-7163.MCT-06-0080
doi: 10.1158/1535-7163.MCT-06-0080
pubmed: 17237261
Zakikhani M, Dowling R, Fantus IG, Sonenberg N, Pollak M (2006) Metformin is an AMP kinase dependent growth inhibitor for BC cells. Cancer Res 66:10269–10273. https://doi.org/10.1158/0008-5472.CAN-06-1500
doi: 10.1158/0008-5472.CAN-06-1500
pubmed: 17062558
Gandini S, Puntoni M, Heckman-Stoddard BM, Dunn BK, Ford L, DeCensi A et al (2014) Metformin and cancer risk and mortality: a systematic review and meta-analysis taking into account biases and confounders. Cancer Prev Res 7:867–885. https://doi.org/10.1158/1940-6207.CAPR-13-0424
doi: 10.1158/1940-6207.CAPR-13-0424
Bonanni B, Puntoni M, Cazzaniga M, Pruneri G, Serrano D, Guerrieri-Gonzaga A et al (2012) Dual effect of metformin on BC proliferation in a randomized presurgical trial. J Clin Oncol 30:2593–2600. https://doi.org/10.1200/JCO.2011.39.3769
doi: 10.1200/JCO.2011.39.3769
pubmed: 22564993
Goodwin PJ, Parulekar WR, Gelmon KA, Shepherd LE, Ligibel JA, Hershman DL et al (2015) Effect of metformin vs placebo on and metabolic factors in NCIC CTG MA.32. J Natl Cancer Inst 107:1–8. https://doi.org/10.1093/jnci/djv006
doi: 10.1093/jnci/djv006
Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC et al (2004) Circulating tumor cells, disease progression, and survival in metastatic BC. N Engl J Med 351:781–791. https://doi.org/10.1056/NEJMoa040766
doi: 10.1056/NEJMoa040766
pubmed: 15317891
Hayes DF, Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Miller MC et al (2006) Circulating tumor cells at each follow-up time point during therapy of metastatic BC patients predict progression-free and overall survival. Clin Cancer Res 12:4218–4224. https://doi.org/10.1158/1078-0432.CCR-05-2821
doi: 10.1158/1078-0432.CCR-05-2821
pubmed: 16857794
De Bono J, Attard G, Adjei A, Pollak MN, Fong PC, Haluska P et al (2007) Potential applications for circulating tumor cells expressing the insulin-like growth factor-I receptor. Clin Cancer Res 13:3611–3616. https://doi.org/10.1158/1078-0432.CCR-07-0268
doi: 10.1158/1078-0432.CCR-07-0268
pubmed: 17575225
Bahr C, Groner B (2005) The IGF-1 receptor and its contributions to metastatic tumor growth-novel approaches to the inhibition of IGF-1R function. Growth Factors 23:1–14. https://doi.org/10.1080/08977190400020229
doi: 10.1080/08977190400020229
pubmed: 16019422
Nanni O, Amadori D, De Censi A, Rocca A, Freschi A, Bologna A et al (2019) Metformin plus chemotherapy versus chemotherapy alone in the first- line treatment of HER2-negative metastatic BC. The MYME randomized, phase 2 clinical trial. BC Res Treat 174:433–442. https://doi.org/10.1007/s10549-018-05070-2
doi: 10.1007/s10549-018-05070-2
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419. https://doi.org/10.1007/bf00280883
doi: 10.1007/bf00280883
pubmed: 3899825
Bonora E, Kiechl S, Willeit J, Oberhollenzer F, Egger G, Meigs JB et al (1998) Prevalence of insulin resistance in metabolic disorders: the Bruneck study. Diabetes 47:1643–1649. https://doi.org/10.2337/dc06-0919
doi: 10.2337/dc06-0919
pubmed: 9753305
Bidard FC, Peeters DJ, Fehm T, Nolé F, Gisbert-Criado R, Mavroudis D et al (2014) Clinical validity of circulating tumour cells in patients with metastatic BC: a pooled analysis of individual patient data. Lancet Oncol 15:406–414. https://doi.org/10.1016/S1470-2045(14)70069-5
doi: 10.1016/S1470-2045(14)70069-5
pubmed: 24636208
Rossi E, Basso U, Celadin R, Zilio F, Pucciarelli S, Aieta M et al (2010) M30 neoepitope expression in epithelial cancer: quantification of apoptosis in circulating tumor cells by cell Search analysis. Clin Cancer Res 16:5233–5243. https://doi.org/10.1158/1078-0432.CCR-10-1449
doi: 10.1158/1078-0432.CCR-10-1449
pubmed: 20978147
Nakae J, Kido Y, Accili D (2010) Distinct and overlapping functions of insulin and IGF-I receptors. Endocr Rev 22:818–835. https://doi.org/10.1210/edrv.22.6.0452
doi: 10.1210/edrv.22.6.0452
Iams WT, Lovly CM (2015) Molecular pathways: clinical applications and future direction of insulin-like growth Factor-1 receptor pathway blockade. Clin Cancer Res 21:4270–4277. https://doi.org/10.1158/1078-0432.CCR-14-2518
doi: 10.1158/1078-0432.CCR-14-2518
pubmed: 26429980
pmcid: 4593065
Cristofanilli M, Pierga JY, Reuben J, Rademaker A, Davis AA, Peeters DJ et al (2019) The clinical use of circulating tumor cells (CTCs) enumeration for staging of metastatic BC (MBC): international expert consensus paper. Crit Rev Oncol Hematol 134:39–45. https://doi.org/10.1016/j.critrevonc.2018.12.004
doi: 10.1016/j.critrevonc.2018.12.004
pubmed: 30771872
Pizon M, Zimon DS, Pachmann U, Pachmann K (2013) Insulin-like growth factor receptor I (IGF-IR) and vascular endothelial growth factor receptor 2 (VEGFR-2) are expressed on the circulating epithelial tumor cells of BC patients. PLoS ONE 8:e56836. https://doi.org/10.1371/journal.pone.0056836
doi: 10.1371/journal.pone.0056836
pubmed: 23418605
pmcid: 3572071
Spiliotaki M, Mavroudis D, Kokotsaki M, Vetsika EK, Stoupis I, Matikas A et al (2018) Expression of insulin-like growth factor-1 receptor in circulating tumor cells of patients with BC is associated with patient outcomes. Mol Oncol 12:21–32. https://doi.org/10.1002/1878-0261.12114
doi: 10.1002/1878-0261.12114
pubmed: 28766847
Pennisi PA, Barr V, Nunez NP, Stannard B, Le RD (2002) Reduced expression of insulin-like growth factor I receptors in MCF-7 BC cells leads to a more metastatic phenotype. Cancer Res 62:6529–6537. https://doi.org/10.1210/en.2006-0311
doi: 10.1210/en.2006-0311
pubmed: 12438247
Jones RA, Moorehead RA (2008) The impact of transgenic IGF-IR overexpression on mammary development and tumorigenesis. J Mammary Gland Biol Neoplasia 13:407–413. https://doi.org/10.1007/s10911-008-9097-1
doi: 10.1007/s10911-008-9097-1
pubmed: 19002570