mTOR Inhibitors, a New Era for Metastatic Luminal HER2-Negative Breast Cancer? A Systematic Review and a Meta-Analysis of Randomized Trials
Open accessAbstract
We evaluated if standard hormonal therapy (HT) could be improved by the addition of mammalian target of rapamycin inhibitors (mTOR-I) in metastatic luminal breast cancer. A meta-analysis on 4 phase II-III randomized clinical trials was performed. Pooled hazard ratio (HR) for progression free survival (PFS)/ time to progression (TTP) was 0.62 in favor of mTOR-I+HT arm (95% confidence interval [CI] 0.55-0.70; p<0.0001). There was significant heterogeneity for PFS/TTP (Cochran's Q 32, p<0.0001, I2 index 90.6%). Pooled HR for overall survival (OS) was 0.84 in favor of the combination arm (95% CI 0.71-0.99; p=0.04). Heterogeneity was not significant (Cochran's Q 4.47, p=0.1, I2 index 55.3%). Pooled risk ratio (RR) for objective response rate (ORR) was 0.88 in favor of experimental arm (95% CI 0.85-0.91; p<0.0001). Heterogeneity was not significant (Cochran's Q 2.11, p=0.3, I2 index 5.2%). Adverse events (AEs), in particular those of grade 3-4, mostly occurred in mTOR-I+HT arm. Combination therapy of HT plus mTOR-I improves the outcome of metastatic luminal breast cancer patients. Our results provide evidence of a class-effect of these targeting molecules.
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mTOR inhibitors could inhibit tumor progression as having a complex modifying role on metabolism.
“mTOR inhibitors could inhibit tumor progression as having a complex modifying role on metabolism [108–113].”
From Hypoxia Signaling in Cancer: From Basics to Clinical Practice (2021) · cites this paper as [110]
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Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement
Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G., & for the PRISMA Group (2009) · BMJ · doi:10.1136/bmj.b2535 · Cited by 83,823 · see citing works
Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement
Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G., & The PRISMA Group (2009) · PLoS Medicine · doi:10.1371/journal.pmed.1000097 · Cited by 64,042 · see citing works
Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement.
(2009) · PubMed Central · Cited by 44,859 · see citing works
Wang, G., Ma, R., Qiao, G., Wada, K., Aizawa, Y., & Satoh, T. (2015) · Integrative Medicine International · doi:10.1159/000368408 · Cited by 18,759 · see citing works
Molecular portraits of human breast tumours
Perou, C., Sørlie, T., Eisen, M., van de Rijn, M., Jeffrey, S., Rees, C. A., Pollack, J., Ross, D., Johnsen, H., Akslen, L., et al. (2000) · Nature · doi:10.1038/35021093 · Cited by 16,551 · see citing works
Nishimura, R., Osako, T., Nishiyama, Y., Tashima, R., Nakano, M., Fujisue, M., Toyozumi, Y., & Arima, N. (2013) · Oncology · doi:10.1159/000353099 · Cited by 13,239 · see citing works
Sørlie, T., Perou, C., Tibshirani, R., Aas, T., Geisler, S., Johnsen, H., Hastie, T., Eisen, M., van de Rijn, M., Jeffrey, S., et al. (2001) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.191367098 · Cited by 11,695 · see citing works
Ki67 expression in breast cancer
Elkablawy, M. A., Albasri, A. M., Mohammed, R. A., Hussainy, A. S., Nouh, M. M., & Alhujaily, A. S. (2016) · Saudi Medical Journal · doi:10.15537/smj.2016.2.12285 · Cited by 4,382 · see citing works
Everolimus in Postmenopausal Hormone-Receptor–Positive Advanced Breast Cancer
Baselga, J., Campone, M., Piccart, M., Burris, H. A., Rugo, H. S., Sahmoud, T., Noguchi, S., Gnant, M., Pritchard, K. I., Lebrun, F., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1109653 · Cited by 2,863 · see citing works
Bachelot, T., Bourgier, C., Cropet, C., Ray-Coquard, I. L., Ferrero, J.-., Freyer, G., Abadie‐Lacourtoisie, S., Eymard, J., Debled, M., Spaëth, D., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.39.0708 · Cited by 702 · see citing works
Baselga, J. M., Семиглазов, В. Ф., van Dam, P., Manikhas, A., Bellet, M., Mayordomo, J. I., Campone, M., Kubista, E., Greil, R., Bianchi, G., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.18.8391 · Cited by 635 · see citing works
Piccart, M., Hortobagyi, G. N., Campone, M., Pritchard, K. I., Lebrun, F., Ito, Y., Noguchi, S., Perez, A., Rugo, H. S., Deleu, I., et al. (2014) · Annals of Oncology · doi:10.1093/annonc/mdu456 · Cited by 574 · see citing works
TOR signalling in bugs, brain and brawn
Jacinto, E., & Hall, M. N. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1018 · Cited by 560 · see citing works
Yardley, D. A., Noguchi, S., Pritchard, K. I., Burris, H. A., Baselga, J. M., Gnant, M., Hortobágyi, G. N., Campone, M., Pistilli, B., Piccart, M. J., et al. (2013) · Advances in Therapy · doi:10.1007/s12325-013-0060-1 · Cited by 522 · see citing works
deGraffenried, L. A., Friedrichs, W. E., Russell, D. H., Donzis, E. J., Middleton, A. K., Silva-Fisher, J., Roth, R. A., & Hidalgo, M. M. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-0035 · Cited by 387 · see citing works
Wolff, A. C., Lazar, A. A., Bondarenko, I., Garin, A. M., Brincat, S., Chow, L. W. C., Sun, Y. P., Nešković‐Konstantinović, Z., Guimarães, R. C., Fumoleau, P., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.38.3331 · Cited by 272 · see citing works
Role of mTOR in anticancer drug resistance: Perspectives for improved drug treatment
Jiang, B., & Liu, L.-Z. (2008) · Drug Resistance Updates · doi:10.1016/j.drup.2008.03.001 · Cited by 240 · see citing works
Granville, C. A., Memmott, R. M., Gills, J. J., & Dennis, P. A. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-1654 · Cited by 181 · see citing works
Akt-induced endocrine therapy resistance is reversed by inhibition of mTOR signaling
Beeram, M., Tan, Q.-T. N., Tekmal, R., Russell, D., Middleton, A. K., & deGraffenried, L. A. (2007) · Annals of Oncology · doi:10.1093/annonc/mdm170 · Cited by 170 · see citing works
Identification of TOR Signaling Complexes
Abraham, R. T. (2002) · Cell · doi:10.1016/s0092-8674(02)01009-7 · Cited by 148 · see citing works
Rugo, H. S., Pritchard, K. I., Gnant, M., Noguchi, S., Piccart, M. J., Hortobágyi, G. N., Baselga, J. M., Perez, A., Geberth, M., Csőszi, T., et al. (2014) · Annals of Oncology · doi:10.1093/annonc/mdu009 · Cited by 131 · see citing works
Carpenter, J. T., Roche, H. H., Campone, M., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.23.16_suppl.564 · Cited by 98 · see citing works
Campone, M., Bachelot, T., Gnant, M., et al. (2013) · European Journal of Cancer · doi:10.1016/j.ejca.2013.04.011 · Cited by 60 · see citing works
Dual Inhibitors of PI3K/mTOR or mTOR-Selective Inhibitors: Which Way Shall We Go?
Sabbah, D. A., Brattain, M. G., & Zhong, H. A. (2011) · Current Medicinal Chemistry · doi:10.2174/092986711798347298 · Cited by 53 · see citing works
Cash, H. A., Shah, S., Moore, E. C., Caruso, A. M., Uppaluri, R., Waes, C. V., & Allen, C. T. (2015) · Oncotarget · doi:10.18632/oncotarget.5063 · Cited by 52 · see citing works
Bhattacharvva, G. S., Biswas, J., Singh, J., et al. (2011) · European Journal of Cancer · doi:10.1016/s0959-8049(11)70115-0 · Cited by 28 · see citing works
Polo, M. L., Riggio, M., May, M., Rodriguez, M. J., Perrone, M. C., Stallings‐Mann, M. L., Kaen, D. L., Frost, M. H., Goetz, M. P., Boughey, J. C., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.4203 · Cited by 26 · see citing works
Diaby, V., Adunlin, G., Zeichner, S. B., et al. (2014) · Breast Cancer Research and Treatment · doi:10.1007/s10549-014-3042-3 · Cited by 19 · see citing works
Advances in the treatment of luminal breast cancer
Howell, S. J. (2013) · Current Opinion in Obstetrics & Gynecology · doi:10.1097/gco.0b013e32835c0410 · Cited by 16 · see citing works
Herrera-Abreu, M. T., Asghar, U. S., Elliot, R., et al. (2015) · Annals of Oncology · doi:10.1093/annonc/mdv120.01 · Cited by 8 · see citing works
Gregor, M. C.-M., Barlow, W. E., Pusztai, L., et al. (2015) · Journal of Clinical Oncology · Cited by 8 · see citing works
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Hypoxia Signaling in Cancer: From Basics to Clinical Practice
Sebestyén, A., Kopper, L., Dankó, T., & Tímár, J. (2021) · Pathology and Oncology Research · doi:10.3389/pore.2021.1609802 · Cited by 110 · see citing works
- Authors
- Rotundo, M. S., Galeano, T., Tassone, P., & Tagliaferri, P.
- Affiliations
- Magna Graecia University (IT)
- Corresponding author
- Tagliaferri, Pierosandro
- Venue
- Oncotarget
- Publisher
- Impact Journals, LLC
- Published
- 2016-02-17
- Volume
- 7
- Issue
- 19
- Pages
- 27055-27066
- ISSN
- 1949-2553 (ISSN-L)
- PMC
- PMC5053632
- OpenAlex
- W2276941569
- Cited by
- 18
- References
- 31
- Citations by year
- 2024: 2 · 2021: 4 · 2020: 4 · 2019: 1 · 2018: 5 · 2017: 1 · 2016: 1
- FWCI
- 0.46
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by
- Locations
- Oncotarget (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Advanced Breast Cancer Therapies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Keywords
- mTOR inhibitors, HER2-negative breast cancer, hormone therapy, combination therapy, progression-free survival, overall survival, objective response rate, adverse events, targeted therapy
- MeSH terms
- Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Humans, Neoplasm Metastasis, Tamoxifen, Proportional Hazards Models, Randomized Controlled Trials as Topic, Outcome Assessment, Health Care, Clinical Trials, Phase II as Topic, Clinical Trials, Phase III as Topic, Disease-Free Survival, Erb-b2 Receptor Tyrosine Kinases, Receptor, ErbB-2, Antineoplastic Agents, Hormonal, Sirolimus, TOR Serine-Threonine Kinases
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