ESR1 Mutations in Asian ER+ Metastatic Breast Cancer on Hormonal Therapy-based Treatments

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

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.

Study Overview

• Status: Unknown
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Hormonal therapy-based treatments

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.

• Study Type: Observational
• Enrollment (Actual): 123

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taipei, Taiwan, 114
    • Tri-Service General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

Asian ER positive/HER2 negative metastatic breast cancer

Description

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.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The percentage of ESR1 LBD mutation variant	The percentage of each ESR1 LBD mutation variant in Asian ER-positive/HER2-negative MBC who had received at least one line of HT	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	PFS of patients who are treated with everolimus plus HT with either ESR1 wild type or different Asian-specific prevalent ESR1 LBD mutation variants such as Y537C	12 months

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Collaborators: Novartis
• Investigators: Principal Investigator: Yen-Shen Lu, MD, PhD, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2017
• Primary Completion (Actual): February 1, 2020
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: December 25, 2019
• First Submitted That Met QC Criteria: December 25, 2019
• First Posted (Actual): December 27, 2019

Study Record Updates

• Last Update Posted (Actual): January 12, 2021
• Last Update Submitted That Met QC Criteria: January 11, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Everolimus
• Other Study ID Numbers: 201703138RIPD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No