Personalized Detection of ctDNA for Patients With HER2-Positive Metastatic Breast Cancer Patients Who Achieved Durable Response to Anti-HER2 Treatment (HER2 CR)

Personalized Detection of ctDNA for Patients With HER2-Positive Metastatic Breast Cancer Who Achieved Durable Response by Anti-HER2 Treatment

Anti-HER2 therapy, such as trastuzumab and pertuzumab, has significantly improved long-term survival in HER2-positive breast cancer. The updated data of the CLEOPATRA trial showed significant Kaplan-Meier curves, suggesting the potential for a cure. However, the efficacy of maintenance therapy in long-term responders remains unexplored. This study will assess MRD in unresectable HER2-positive breast cancer cases with long-term response using the Signatera™ ctDNA assay, which could contribute to future treatment strategy development.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer, Metastatic; HER2 + Breast Cancer
• Intervention / Treatment: Drug: Trastuzumab (Herceptin); Diagnostic test: SIgnatera

Detailed Description

More than 20 years have passed since the introduction of trastuzumab as a treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The additive effect of trastuzumab, an anti-HER2 antibody, was evaluated in combination with chemotherapy (paclitaxel or anthracycline plus cyclophosphamide) in previously untreated, unresectable HER2-positive breast cancer. The number of cases achieving long-term survival with anti-HER2 therapy has been increasing, and this trend is also observed in our institution.

The treatment for unresectable breast cancer is systemic therapy, which is typically continued as long as it remains effective and side effects are tolerable. However, in cases of long-term response in HER2-positive breast cancer, the impact of continuing anti-HER2 therapy alone as maintenance therapy on prognosis and the safety of treatment discontinuation remains unclear.

In recent years, the clinical application of circulating tumor DNA (ctDNA) has attracted attention for early diagnosis and detection of minimal residual disease. Signatera™, an assay developed by Natera Inc., detects minimal residual disease. It is a personalized ctDNA test for individual patients, and a study targeting breast cancer patients post-surgery reported a detection sensitivity exceeding 90% for variant allele frequencies (VAF) as low as 0.01%. This high sensitivity has been reported not only in breast cancer but also in other cancer types. However, there have been no reports of Signatera analysis in unresectable breast cancer.

In this study, investigators will use Signatera™ to evaluate and analyze ctDNA status (ctDNA positive or negative) in cases of unresectable HER2-positive breast cancer that have achieved long-term response. By assessing ctDNA in such cases, this study may lead to new therapeutic strategies, such as de-escalating anti-HER2 therapy in ctDNA-negative cases.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

Study Locations

• Japan
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 4678601
      • Aichi Cancer Center
    • Nagoya, Aichi-ken, Japan, 4678601
      • Nagoya City University
  • Tokyo
    • Tokyo, Tokyo, Japan, 135-8550
      • The Cancer Institute Hospital of Japanese Foundation for Cancer Research
• United States
  • Texas
    • San Carlos, Texas, United States, 94070
      • Natera

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The eligibility criteria for this study include patients who have been diagnosed with histologically confirmed invasive breast cancer and unresectable HER2-positive breast cancer. Eligible cases are those in which drug therapy, including anti-HER2 therapy, was initiated between January 1, 2000, and December 31, 2021. Additionally, patients must have maintained a partial or complete response to drug therapy, including anti-HER2 therapy, for more than two years. Finally, the study is limited to female patients aged 20 years or older.

Description

Inclusion Criteria:

• HER2 + metastatic breast cancer
• Pre / post menopausal
• Previously treated with anti-HER2 therapy
• Continuing CR or PR for more than 2 year

Exclusion Criteria:

• Patients who were deemed inappropriate as research subjects based on the physician's judgment, such as those possibly receiving inappropriate treatment.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Continuing anti-HER2 treatment; Breast cancer patients who are continuing complete response (CR) or partial response (PR) for more than two years of anti-HER2 treatment (trastuzumab, pertuzumab, T-DM1, and T-DXd)	Drug: Trastuzumab (Herceptin); Continuing anti-HER2 treatment; Other Names: Trastuzumab Emtansine; Trastuzumab Deruxtecan; Diagnostic test: SIgnatera; A personalized, tumor-informed test.
Follow up (stop anti-HER2 treatment); Breast cancer patients who stopped anti-HER2 treatment with complete response (CR) or partial response (PR) after more than two years of anti-HER2 treatment(trastuzumab, pertuzumab, T-DM1, and T-DXd)	Diagnostic test: SIgnatera; A personalized, tumor-informed test.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The status of ctDNA	To assess the status of ctDNA in CR patients with/without continuing treatment, or PR patients with continuing treatment	1 year

Collaborators and Investigators

• Sponsor: Nagoya City University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: October 24, 2024
• First Submitted That Met QC Criteria: October 25, 2024
• First Posted (Actual): October 29, 2024

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: minimal residual disease; HER2+ breast cancer; MRD; ctDNA monitoring; Dual response
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplastic Processes; Skin Diseases; Breast Diseases; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Neoplasm, Residual; Breast Neoplasms; Neoplasm Metastasis; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Polycyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Macrolides; Lactones; Lactams, Macrocyclic; Macrocyclic Compounds; Maytansine; Trastuzumab; Ado-Trastuzumab Emtansine; trastuzumab deruxtecan
• Other Study ID Numbers: HER2 CR; 80-24-0057 (Other Identifier: Nagoya City Unversity)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No