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Plasma ESR1 Mutations and the Treatment of Estrogen Receptor–Positive Advanced Breast Cancer
- Source :
- Journal of Clinical Oncology. 34:2961-2968
- Publication Year :
- 2016
- Publisher :
- American Society of Clinical Oncology (ASCO), 2016.
-
Abstract
- Purpose ESR1 mutations are selected by prior aromatase inhibitor (AI) therapy in advanced breast cancer. We assessed the impact of ESR1 mutations on sensitivity to standard therapies in two phase III randomized trials that represent the development of the current standard therapy for estrogen receptor–positive advanced breast cancer. Materials and Methods In a prospective-retrospective analysis, we assessed ESR1 mutations in available archived baseline plasma from the SoFEA (Study of Faslodex Versus Exemestane With or Without Arimidex) trial, which compared exemestane with fulvestrant-containing regimens in patients with prior sensitivity to nonsteroidal AI and in baseline plasma from the PALOMA3 (Palbociclib Combined With Fulvestrant in Hormone Receptor–Positive HER2-Negative Metastatic Breast Cancer After Endocrine Failure) trial, which compared fulvestrant plus placebo with fulvestrant plus palbociclib in patients with progression after receiving prior endocrine therapy. ESR1 mutations were analyzed by multiplex digital polymerase chain reaction. Results In SoFEA, ESR1 mutations were found in 39.1% of patients (63 of 161), of whom 49.1% (27 of 55) were polyclonal, with rates of mutation detection unaffected by delays in processing of archival plasma. Patients with ESR1 mutations had improved progression-free survival (PFS) after taking fulvestrant (n = 45) compared with exemestane (n = 18; hazard ratio [HR], 0.52; 95% CI, 0.30 to 0.92; P = .02), whereas patients with wild-type ESR1 had similar PFS after receiving either treatment (HR, 1.07; 95% CI, 0.68 to 1.67; P = .77). In PALOMA3, ESR1 mutations were found in the plasma of 25.3% of patients (91 of 360), of whom 28.6% (26 of 91) were polyclonal, with mutations associated with acquired resistance to prior AI. Fulvestrant plus palbociclib improved PFS compared with fulvestrant plus placebo in both ESR1 mutant (HR, 0.43; 95% CI, 0.25 to 0.74; P = .002) and ESR1 wild-type patients (HR, 0.49; 95% CI, 0.35 to 0.70; P < .001). Conclusion ESR1 mutation analysis in plasma after progression after prior AI therapy may help direct choice of further endocrine-based therapy. Additional confirmatory studies are required.
- Subjects :
- 0301 basic medicine
Oncology
Cancer Research
medicine.medical_specialty
Pyridines
medicine.drug_class
Estrogen receptor
Anastrozole
Breast Neoplasms
Palbociclib
Pharmacology
Disease-Free Survival
Piperazines
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Exemestane
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
Nitriles
medicine
Humans
Prospective Studies
Fulvestrant
Aged
Retrospective Studies
Aromatase inhibitor
Estradiol
business.industry
Estrogen Receptor alpha
Cancer
DNA, Neoplasm
Middle Aged
Triazoles
medicine.disease
Metastatic breast cancer
Androstadienes
030104 developmental biology
chemistry
030220 oncology & carcinogenesis
Female
business
medicine.drug
Subjects
Details
- ISSN :
- 15277755 and 0732183X
- Volume :
- 34
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Oncology
- Accession number :
- edsair.doi.dedup.....bef7c277badd8d333fd46c9292a921dd