The purpose of the study is to determine the diagnostic role of ctDNA when used to monitor metastatic breast cancer (MBC) during first-line endocrine therapy.
Patients with hormone receptor-positive MBC are eligible for endocrine therapy (ET) as first line treatment which is based on strategies aimed to either block signaling pathways depending on the estrogen receptor (ESR1) or using ESR1 antagonists. Only a few accepted predictive factors are associated with treatment benefit for MBC (i.e., hormone receptor status and HER2 status). Furthermore, a standardized assessment evaluation for MBC is still lacking. Because of these unmet needs, ET is continued until disease progression, or if toxicity requiring discontinuation occurs. Resistance is frequent in the treatment of early BC and unavoidable in MBC. Recently, mutations in ESR1 have been described in MBC that had been previously exposed to aromatase inhibitors (AIs) and are rarely detectable in primary BC. Besides that, resistance phenomena have been also linked to ESR1 cisregulatory elements (CRE, i.e. enhancers and promoters) hypermethylation, both related to ESR1 silencing. According to the literature, the aim of the study is to detect tumor response with liquid biopsy technique compared to conventional clinical pratice algorithms.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
164
CT scan and liquid biopsy blood sample are performed at baseline, after 8 weeks from baseline and, then, every 12 weeks. Between two subsequent CT scan another liquid biopsy blood sample is performed. CEA and CA 15.3 will be performed at baseline and then concomitantly to the radiological evaluation
Asst Papa Giovanni Xxiii- Bergamo
Bergamo, Bergamo, Italy
RECRUITINGCentro di Riferimento Oncologico - Aviano
Aviano, Pordenone, Italy
RECRUITINGAsst Ospedali Civili Di Brescia
Brescia, Italy
RECRUITINGAzienda Ospedaliero Universitaria Policlinico G. Rodolico- San Marco-Catania
Catania, Italy
RECRUITINGUniversita' Degli Studi Di Napoli Federico Ii
Napoli, Italy
RECRUITINGazienda sanitaria universitaria friuli centrale- Udine
Udine, Italy
RECRUITINGOspedale San Bortolo- Azienda Ulss8 Berica
Vicenza, Italy
RECRUITINGLiquid-biopsy in monitoring treatment response in luminal breast cancer
The primary objective of this study is to evaluate whether liquid-biopsy technique is able to detect treatment response in luminal breast cancer through the quantification of ESR1 ctDNA mutations
Time frame: 3 years
ctDNA/miRNA based follow-up
To characterize the clinical implications of deploying a ctDNA/miRNA based follow-up both in terms of outcome and health systems management.
Time frame: 3 years
Treatment resistance mechanisms
To investigate treatment resistance mechanisms and their detectability through ctDNA/miRNA analysis.
Time frame: 3 years
Specificity
The proportion of patients correctly classified with a stable or response disease through the genetic and epigenetic analysis of ESR1 ctDNA among those without clinicoradiological relapse.
Time frame: From baseline until disease progression
Positive predictive value
The proportion of patients correctly classified with a progressive disease through the genetic and epigenetic analysis of ESR1 ctDNA (i.e. those patients with molecular progression that is confirmed by clinic-radiological progression) among all patients with molecular progression (i.e. patients who show molecular progression irrespectively of clinic-radiological progression).
Time frame: 3 years
Negative predictive value
The proportion of patients correctly classified with a stable or response among those without clinico-radiological relapse.
Time frame: 3 years
Accuracy
Accuracy of the ESR1 ctDNA test in respect to correctly classify the patients with clinicoradiological relapse and without clinico-radiological relapse at 6 months.
Time frame: 6 months
Lead time (for PFS)
The time elapsed between the molecular detected progression and the imaging assessed one.
Time frame: 3 years
Number of futile diagnostic imaging
The number of imaging evaluations negative for progression and that could be avoided with the liquid biopsy technique.
Time frame: 3 years
Time to Progression (TTP)
The time from first biomarker assessment until objective tumor progression.
Time frame: 3 years
Progression Free Survival (PFS)
The time from first biomarker assessment until objective tumor progression or death for any cause, whichever comes first.
Time frame: 3 years
Overall Survival (OS)
The time from first biomarker assessment until death from any cause.
Time frame: 3 years
Overall Response Rate (ORR)
The sum of partial responses (PR) and complete responses (CR) evaluated from the time of first biomarker assessment to documented disease progression.
Time frame: 3 years
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