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Niu J, Andres G, Kramer K, et al. Incidence and clinical significance of ESR1 mutations in heavily pretreated metastatic breast cancer patients. Onco Targets Ther. 2015;8:3323-8doi: 10.2147/OTT.S92443.
Niu, J., Andres, G., Kramer, K., Kundranda, M. N., Alvarez, R. H., Klimant, E., Parikh, A. R., Tan, B., Staren, E. D., & Markman, M. (2015). Incidence and clinical significance of ESR1 mutations in heavily pretreated metastatic breast cancer patients. OncoTargets and therapy, 83323-8. https://doi.org/10.2147/OTT.S92443
Niu, Jiaxin, et al. "Incidence and clinical significance of ESR1 mutations in heavily pretreated metastatic breast cancer patients." OncoTargets and therapy vol. 8 (2015): 3323-8. doi: https://doi.org/10.2147/OTT.S92443
Niu J, Andres G, Kramer K, Kundranda MN, Alvarez RH, Klimant E, Parikh AR, Tan B, Staren ED, Markman M. Incidence and clinical significance of ESR1 mutations in heavily pretreated metastatic breast cancer patients. Onco Targets Ther. 2015 Nov 11;8:3323-8. doi: 10.2147/OTT.S92443. eCollection 2015. PMID: 26648736; PMCID: PMC4648593.
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Onco Targets Ther. 2015 Nov 11;8:3323-8. doi: 10.2147/OTT.S92443. eCollection 2015.

Incidence and clinical significance of ESR1 mutations in heavily pretreated metastatic breast cancer patients.

OncoTargets and therapy

Jiaxin Niu, Grant Andres, Kim Kramer, Madappa N Kundranda, Ricardo H Alvarez, Eiko Klimant, Ankur R Parikh, Bradford Tan, Edgar D Staren, Maurie Markman

Affiliations

  1. Department of Medical Oncology, Western Regional Medical Center at Cancer Treatment Centers of America (CTCA), Goodyear, AZ, USA.
  2. CTCA Medicine and Science, Zion, IL, USA.
  3. Department of Medical Oncology, Banner MD Anderson Cancer Center, Gilbert, AZ, USA.
  4. Department of Medical Oncology, Southeastern Regional Medical Center at CTCA, Newnan, GA, USA.
  5. Department of Medical Oncology, Eastern Regional Medical Center at CTCA, Philadelphia, PA, USA.
  6. Department of Pathology, Midwestern Regional Medical Center at CTCA, Zion, IL, USA.
  7. Advanced Individual Medicine, Phoenix, AZ, USA.
  8. CTCA Medicine and Science, Philadelphia, PA, USA.

PMID: 26648736 PMCID: PMC4648593 DOI: 10.2147/OTT.S92443

Abstract

BACKGROUND: ESR1 mutation has recently emerged as one of the important mechanisms involved in endocrine resistance. The incidence and clinical implication of ESR1 mutation has not been well evaluated in heavily pretreated breast cancer patients.

METHODS: We conducted a retrospective review of advanced breast cancer patients with tumors who underwent next-generation sequencing genomic profiling using Foundation One test at Cancer Treatment Centers of America(®) regional hospitals between November 2012 and November 2014.

RESULTS: We identified a total of 341 patients including 217 (59%) estrogen receptor (ER)+, 177 (48%) progesterone receptor (PR)+, 30 (8%) hormone receptor+/HER2 positive, and 119 (32%) triple negative patients. ESR1 mutation was noted in 27/222 (12.1%) ER+ or PR+ breast cancer patients. All ER+ patients received at least one line of an aromatase inhibitor. All 28 patients were found to harbor ESR1 mutations affecting ligand-binding domain with the most common mutations affecting Y537 (17/28, 60.7%) and D538 (9/28, 32.1%). In this cohort, 19 (67.9%) patients carried three or more, seven (25%) patients had one or two additional genomic alterations and one (3.6%) patient had an ESR1 mutation only. Of 28 patients, three patients were treated with fulvestrant immediately before and two patients were treated after next-generation sequencing testing; only one patient achieved stable disease for 8 months and the other four patients had progression of disease. In all, 3/3 (100%) patients before testing and 2/4 (50%) after testing treated with exemestane and everolimus achieved stable disease for at least 6 months.

CONCLUSION: ESR1 mutation was found in 12.1% of a large cohort of advanced breast cancer patients. Exemestane in combination with everolimus might be a reasonable option. Prospective studies are warranted to validate these findings.

Keywords: ESR1 mutation; breast cancer; endocrine therapy; genomic alteration; next-generation sequencing; resistance

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