We hypothesize that patients with detectable ESR1 mutations in cell-free DNA benefit from chemotherapy, resulting in improved PFS.
ID
Bron
Verkorte titel
Aandoening
breast cancer, metastasis, ESR1 mutations, chemotherapy
Ondersteuning
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
To establish whether patients with ER-positive, HER2- negative MBC with an ESR1 mutation will benefit from taxane based chemotherapy, measured as progression free survival rate at 6 months.
Achtergrond van het onderzoek
Endocrine treatment is the mainstay of treatment for ER- positive metastatic breast cancer (MBC). Unfortunately, 40% of patients have no clinical benefit from first-line endocrine therapy due to intrinsic resistance, whereas the remainder of patients initially responding will eventually develop resistance during therapy. Importantly, once the tumor develops resistance to endocrine therapy, the tumor becomes more aggressive, leading to a poor prognosis. Recently, mutations in the gene encoding ERá, ESR1, have attracted
particular interest as a mechanism for endocrine resistance in MBC. Since the ESR1 mutated cells grow independently from estrogen, we hypothesize that these tumor cells have higher cell division rates and are therefore more sensitive to the anti-tumor effects from chemotherapy. If this is the case, ESR1 mutated patients would still benefit from chemotherapy, reflected in an improved PFS. Therefore, we present here a biomarker study to investigate whether ESR1 mutated patients could still benefit from taxane-based chemotherapy.
Doel van het onderzoek
We hypothesize that patients with detectable ESR1 mutations in cell-free DNA benefit from chemotherapy, resulting in improved PFS.
Onderzoeksopzet
- Baseline
- 2 weeks
- 6 weeks
- 3 months
- 6 months: determination of response
- Progression
Onderzoeksproduct en/of interventie
Blood draw for cfDNA isolation (20mL) at baseline, during treatment, after treatment and at progression.
Publiek
A. Jager
Groene Hilledijk 301
Rotterdam 3075 EA
The Netherlands
Tel 010 704 17 33
a.jager@erasmusmc.nl
Wetenschappelijk
A. Jager
Groene Hilledijk 301
Rotterdam 3075 EA
The Netherlands
Tel 010 704 17 33
a.jager@erasmusmc.nl
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
- Female metastatic breast cancer patients with ER-positive, HER2- negative primary tumors;
- Previous treatment with at least an aromatase inhibitor either in adjuvant and/or metastatic setting;
- Considered fit enough to receive taxane-based chemotherapy by the treating physician;
- Intention to start with either paclitaxel or docetaxel as first line treatment for metastatic breast cancer or as second line treatment if the time between completion of first line chemotherapy for metastatic breast cancer and inclusion is more than three years.
- Patient with measurable disease as defined per RECIST1.1 or bone only disease on recent standard work-up for MBC;
- WHO performance status 0-2
- Age > 18 years
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
- Previous chemotherapy for metastatic disease; completed within three years before inclusion
- Patients with locally advanced disease, primary not amendable for resection or
radiation therapy with curative intent;
3- (neo)adjuvant chemotherapy within 6 months prior to treatment start;
- Anti-hormonal treatment for breast cancer within one week prior to treatment start;
- Symptomatic CNS metastasis (the presence of at least one key symptom in combination with radiologic evidence (positive contrast-enhanced CT or MRI of the brain)
- Serious illness or medical unstable condition prohibiting adequate treatment and follow-up.
Opzet
Deelname
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In overige registers
| Register | ID |
|---|---|
| NTR-new | NL7082 |
| NTR-old | NTR7280 |
| CCMO | NL62417.078.17 |
| OMON | NL-OMON46354 |