Mutational Analysis of Circulating Tumor DNA in Patients With Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer Receiving Palbociclib : Results From the TREnd Trial
PURPOSE: To identify prognostic circulating biomarkers to cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i), we performed a mutational analysis on circulating tumor DNA (ctDNA) samples from patients included in the TREnd trial, which randomly assigned patients to receive the CDK4/6i palbociclib alone or with the endocrine treatment (ET) to which they had progressed.
METHODS: Forty-six patients were enrolled in this substudy. Plasma was collected before treatment (T0), after the first cycle of therapy (T1), and at the time of progression (T2). ctDNA hybridization and capture were performed using the Illumina TruSight Tumor 170 Kit. Acquired mutations were confirmed by digital polymerase chain reaction. Progression-free survival analysis was estimated using the Kaplan-Meier method and compared with the log-rank test.
RESULTS: The most frequently mutated genes at T0 were ESR1 (23%), PIK3CA (17%), AR, FGFR2, and TP53 (10%). Mutations in ESR1 at T0 conferred higher risk of progression in the entire population (P = .02) and in patients treated with palbociclib + ET (P = .04). ESR1 mutation effect remained significant after correction for clinical variables (P = .03). PIK3CA mutations at T0 were not prognostic, but higher risk of progression was observed when a broader analysis of PI3K pathway was performed (P = .04). At T2, we observed the emergence of nine new mutations in seven genes.
CONCLUSION: Mutations in ESR1 and in PI3K pathway genes at T0 were associated with worse prognosis in palbociclib-treated patients. We describe the emergence of newly acquired mutations in palbociclib-treated patients, which might potentially affect subsequent treatment.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
|---|---|
| Enthalten in: |
JCO precision oncology - 8(2024) vom: 01. Feb., Seite e2300285 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Migliaccio, Ilenia [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 04.03.2024 Date Revised 09.03.2024 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1200/PO.23.00285 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM369178165 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM369178165 | ||
| 003 | DE-627 | ||
| 005 | 20240309232358.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240302s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1200/PO.23.00285 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1321.xml |
| 035 | |a (DE-627)NLM369178165 | ||
| 035 | |a (NLM)38427931 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Migliaccio, Ilenia |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Mutational Analysis of Circulating Tumor DNA in Patients With Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer Receiving Palbociclib |b Results From the TREnd Trial |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 04.03.2024 | ||
| 500 | |a Date Revised 09.03.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a PURPOSE: To identify prognostic circulating biomarkers to cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i), we performed a mutational analysis on circulating tumor DNA (ctDNA) samples from patients included in the TREnd trial, which randomly assigned patients to receive the CDK4/6i palbociclib alone or with the endocrine treatment (ET) to which they had progressed | ||
| 520 | |a METHODS: Forty-six patients were enrolled in this substudy. Plasma was collected before treatment (T0), after the first cycle of therapy (T1), and at the time of progression (T2). ctDNA hybridization and capture were performed using the Illumina TruSight Tumor 170 Kit. Acquired mutations were confirmed by digital polymerase chain reaction. Progression-free survival analysis was estimated using the Kaplan-Meier method and compared with the log-rank test | ||
| 520 | |a RESULTS: The most frequently mutated genes at T0 were ESR1 (23%), PIK3CA (17%), AR, FGFR2, and TP53 (10%). Mutations in ESR1 at T0 conferred higher risk of progression in the entire population (P = .02) and in patients treated with palbociclib + ET (P = .04). ESR1 mutation effect remained significant after correction for clinical variables (P = .03). PIK3CA mutations at T0 were not prognostic, but higher risk of progression was observed when a broader analysis of PI3K pathway was performed (P = .04). At T2, we observed the emergence of nine new mutations in seven genes | ||
| 520 | |a CONCLUSION: Mutations in ESR1 and in PI3K pathway genes at T0 were associated with worse prognosis in palbociclib-treated patients. We describe the emergence of newly acquired mutations in palbociclib-treated patients, which might potentially affect subsequent treatment | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Circulating Tumor DNA |2 NLM | |
| 650 | 7 | |a palbociclib |2 NLM | |
| 650 | 7 | |a G9ZF61LE7G |2 NLM | |
| 650 | 7 | |a ERBB2 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.10.1 |2 NLM | |
| 650 | 7 | |a Phosphatidylinositol 3-Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.1.- |2 NLM | |
| 650 | 7 | |a Receptors, Estrogen |2 NLM | |
| 650 | 7 | |a Piperazines |2 NLM | |
| 650 | 7 | |a Pyridines |2 NLM | |
| 650 | 7 | |a Receptor, ErbB-2 |2 NLM | |
| 650 | 7 | |a EC 2.7.10.1 |2 NLM | |
| 700 | 1 | |a Romagnoli, Dario |e verfasserin |4 aut | |
| 700 | 1 | |a Galardi, Francesca |e verfasserin |4 aut | |
| 700 | 1 | |a De Luca, Francesca |e verfasserin |4 aut | |
| 700 | 1 | |a Biagioni, Chiara |e verfasserin |4 aut | |
| 700 | 1 | |a Curigliano, Giuseppe |e verfasserin |4 aut | |
| 700 | 1 | |a Criscitiello, Carmen |e verfasserin |4 aut | |
| 700 | 1 | |a Minisini, Alessandro Marco |e verfasserin |4 aut | |
| 700 | 1 | |a Moretti, Erica |e verfasserin |4 aut | |
| 700 | 1 | |a Risi, Emanuela |e verfasserin |4 aut | |
| 700 | 1 | |a Guarducci, Cristina |e verfasserin |4 aut | |
| 700 | 1 | |a Nardone, Agostina |e verfasserin |4 aut | |
| 700 | 1 | |a Biganzoli, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Benelli, Matteo |e verfasserin |4 aut | |
| 700 | 1 | |a Malorni, Luca |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t JCO precision oncology |d 2017 |g 8(2024) vom: 01. Feb., Seite e2300285 |w (DE-627)NLM273576054 |x 2473-4284 |7 nnns |
| 773 | 1 | 8 | |g volume:8 |g year:2024 |g day:01 |g month:02 |g pages:e2300285 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1200/PO.23.00285 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 8 |j 2024 |b 01 |c 02 |h e2300285 | ||