Clinical trial NCT04212702: ESR1 Mutations in Asian ER+ Metastatic Breast Cancer on Hormonal Therapy-based Treatments
Official title: The Landscape of ESR1 Mutations in Asian Estrogen Receptor-positive Metastatic Breast Cancer Patients Detected by Liquid Biopsy and Impact on Hormonal Therapy-based Treatments
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Metastatic Breast Cancer
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2019-12-27
Enrollment: 123
Sex: FEMALE
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Asian ER positive/HER2 negative metastatic breast cancer

Brief summary: The investigator propose a prospective study using blood samples (liquid biopsy) of estrogen receptor (ER)-positive metastatic breast cancer (MBC) patients to understand the prevalence of estrogen receptor 1 (ESR1) mutation variants and the correlation with hormonal therapy (HT)-based treatment resistance in Asian ER-positive/human epidermal growth receptor-2 (HER2)-negative MBC population.

Detailed description: The investigator will use next-generation targeted sequencing covering the entire ESR1 ligand-binding domain (LBD) region to understand 1. the spectrum and prevalence of specific ESR1 mutation variants in Asian women, and 2. the preliminary correlation of Asian-specific prevalent ESR1 LBD mutation variants such as Y537C with treatment efficacy. For the second purpose, the investigator will specifically focus on patients with ESR1 Y537C mutation, while the results from patients with wild type ESR1 and patients with D538G or Y537S mutant will be severed as control for preliminary comparison.

Eligibility criteria: Inclusion Criteria:

* (1) Female patients who are ≥ 20 years old at the time of informed consent.
* (2) Have histologically confirmed ER positive (defined as ≥1%) and/ or progesterone receptor (PR) positive (defined as ≥1%) breast cancer.
* (3) Have histologically confirmed HER2-negative breast cancer as defined by immuno-histochemistry (IHC) ≤ 2+, and/or fluorescence in situ hybridization (FISH) negative.
* (4) Patients who fits either one of the following two criteria are eligible: I. Have radiological or objective evidence of inoperable locally advanced or metastatic breast cancer and are planned to be given HT single agent, HT plus other targeted therapy, HT plus everolimus (reimbursed by National Health Insurance), HT plus metronomic oral chemotherapy or oral chemotherapy only by the treating physician. II. Locally advanced but operable patients before the resection of the primary tumor.

Exclusion Criteria:

* (1) Patients not suitable for oral anti-cancer treatment as determined by the investigator.
* (2) Known hypersensitivity to mammilian target of rapamycin (mTOR) inhibitors, e.g. Sirolimus (rapamycin).
* (3) Patients with a known history of HIV seropositivity. Screening for HIV infection at baseline is not required.
* (4) Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A.

Primary outcomes:
measure: The percentage of ESR1 LBD mutation variant
timeFrame: 12 months
Secondary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: 12 months
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
Study officials:
affiliation: National Taiwan University Hospital
name: Yen-Shen Lu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: