The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
Prevalence of ESR1 Mutations in Cell-Free DNA and Outcomes in Metastatic Breast Cancer: A Secondary Analysis of the BOLERO-2 Clinical Trial
Open accessAbstract
IMPORTANCE: Estrogen receptor α (ESR1) mutations found in metastatic breast cancer (MBC) promote ligand-independent receptor activation and resistance to estrogen-deprivation therapy in laboratory models. The prevalence of these mutations and their potential impact on clinical outcomes has not been established. OBJECTIVE: To determine the prevalence of ESR1 mutations (Y537S and D538G) in estrogen receptor (ER)-positive MBC and determine whether mutation is associated with inferior outcomes. DESIGN, SETTING, AND PARTICIPANTS: From December 16, 2014, to August 26, 2015, we analyzed cell-free DNA (cfDNA) from baseline plasma samples from participants in the BOLERO-2 double-blind phase 3 study that randomized patients from 189 centers in 24 countries with MBC to exemestane plus placebo or exemestane plus everolimus. The study enrolled postmenopausal women with a diagnosis of MBC and prior exposure to an aromatase inhibitor. Baseline plasma samples were available from 541 of 724 patients (74.7%). We assessed the effect of mutation on overall survival of the population and the effect of mutation on progression-free survival (PFS) by treatment arm. INTERVENTIONS: Patients were randomized to treatment with exemestane (25 mg oral daily) together with everolimus (10 mg oral daily) or with placebo. MAIN OUTCOMES AND MEASURES: The 2 most frequent mutations in ESR1 (Y537S and D538G) were analyzed from cfDNA using droplet digital polymerase chain reaction and samples scored as wild-type, D538G, Y537S, or double mutant. Cox-proportional hazards model was used to assess PFS in patient subgroups defined by mutations, and the effect of each mutation on overall survival. RESULTS: Of 541 evaluable patients, 156 (28.8%) had ESR1 mutation D538G (21.1%) and/or Y537S (13.3%), and 30 had both. These mutations were associated with shorter overall survival (wild-type, 32.1 months [95% CI, 28.09-36.40 months]; D538G, 25.99 months [95% CI, 19.19-32.36 months]; Y537S, 19.98 months [13.01-29.31 months]; both mutations, 15.15 months [95% CI, 10.87-27.43 months]). The D538G group (hazard ratio, 0.34 [95% CI, 0.02-0.57]) derived a similar PFS benefit as wild type from addition of everolimus to exemestane. CONCLUSIONS AND RELEVANCE: ESR1 mutations are prevalent in ER-positive aromatase inhibitor-treated MBC. Both Y537S and D538G mutations are associated with more aggressive disease biology. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00863655.
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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
Self-citationHarris, L., Fritsche, H., Mennel, R., Norton, L., Ravdin, P., Taube, S., Somerfield, M. R., Hayes, D. F., & Bast, R. C. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2007.14.2364 · Cited by 2,217
Prospective Validation of a 21-Gene Expression Assay in Breast Cancer
Sparano, J. A., Gray, R. J., Makower, D. F., Pritchard, K. I., Albain, K. S., Hayes, D. F., Geyer, C. E., Dees, E. C., Perez, E. A., Olson, J. A., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1510764 · Cited by 1,388
ESR1 ligand-binding domain mutations in hormone-resistant breast cancer
Toy, W., Shen, Y., Won, H., Green, B., Sakr, R. A., Will, M., Li, Z., Gala, K., Fanning, S., King, T. A., et al. (2013) · Nature Genetics · doi:10.1038/ng.2822 · Cited by 1,248
Self-citationActivating ESR1 mutations in hormone-resistant metastatic breast cancer
Robinson, D. R., Wu, Y.-M., Vats, P., Su, F., Lonigro, R. J., Cao, X., Kalyana-Sundaram, S., Wang, R., Ning, Y., Hodges, L., et al. (2013) · Nature Genetics · doi:10.1038/ng.2823 · Cited by 1,145
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Mouridsen, H., Gershanovich, M., Sun, Y., Pérez-Carrión, R., Boni, C., Monnier, A., Apffelstaedt, J., Smith, R., Sleeboom, H. P., Jaenicke, F., et al. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.04.194 · Cited by 746
Jeselsohn, R., Yelensky, R., Buchwalter, G., Frampton, G., Meric-Bernstam, F., Gonzalez-Angulo, A. M., Ferrer-Lozano, J., Perez-Fidalgo, J. A., Cristofanilli, M., Gómez, H., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-2332 · Cited by 674
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Genomic Evolution of Breast Cancer Metastasis and Relapse
Yates, L. R., Knappskog, S., Wedge, D., Farmery, J. H. R., Gonzalez, S., Martincorena, I., Alexandrov, L. B., Van Loo, P., Haugland, H. K., Lilleng, P. K., et al. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.07.005 · Cited by 665
O'Leary, B., Cutts, R. J., Liu, Y., Hrebien, S., Huang, X., Fenwick, K., André, F., Loibl, S., Loi, S., Garcia-Murillas, I., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0264 · Cited by 650
The emerging role of cell-free DNA as a molecular marker for cancer management
Bronkhorst, A. J., Ungerer, V., & Holdenrieder, S. (2019) · Biomolecular Detection and Quantification · doi:10.1016/j.bdq.2019.100087 · Cited by 566
Morganti, S., Tarantino, P., Ferraro, E., D’Amico, P., Duso, B. A., & Curigliano, G. (2019) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-030-24100-1_2 · Cited by 246
Metadata
- Authors
- Chandarlapaty, S., Chen, D., He, W., Sung, P., Samoila, A., You, D., Bhatt, T., Patel, P., Voi, M., Gnant, M., Hortobagyi, G., Baselga, J., & Moynahan, M. E.
- Venue
- JAMA Oncology
- Publisher
- American Medical Association (AMA)
- Published
- 2016-10-01
- Volume
- 2
- Issue
- 10
- Pages
- 1310
- ISSN
- 2374-2437 (ISSN-L)
- OpenAlex
- W2514365970
- Cited by
- 494
- References
- 15
- FWCI
- 47.40
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Chandarlapaty, S., Chen, D., He, W., Sung, P., Samoila, A., You, D., Bhatt, T., Patel, P., Voi, M., Gnant, M., Hortobagyi, G., Baselga, J., & Moynahan, M. E. (2016). Prevalence of ESR1 Mutations in Cell-Free DNA and Outcomes in Metastatic Breast Cancer: A Secondary Analysis of the BOLERO-2 Clinical Trial. JAMA Oncology. https://doi.org/10.1001/jamaoncol.2016.1279
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