Longitudinal Tumor Burden Quantification Using Circulating Tumor DNA in Metastatic Lobular Breast Cancer (LBC-Monitor)

LBC-Monitor: Liquid Biopsy Guided Tailoring of Therapy in Metastatic Lobular Breast Cancer (mILC): A Pilot Study of Longitudinal Tumor Burden Quantification Using Circulating Tumor DNA

The goal of this study is to characterize early dynamic changes in ctDNA, which can aid in tailoring early therapy in patients with metastatic Invasive lobular carcinoma (ILC). Response assessment using ctDNA analysis could not only aid in de-escalation but also escalation strategies.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Invasive Lobular Carcinoma (mILC)
• Intervention / Treatment: Diagnostic test: circulating tumor DNA (ctDNA)

Detailed Description

Invasive lobular carcinoma (ILC) is the most common special histologic subtype of breast cancer (BC), comprising 10-15% of all invasive BCs and representing approximately 26,000-40,000 new cases annually in the United States. ILC has distinct morphological and biological features as well as clinical behavior compared to Invasive Ductal Carcinoma/breast carcinoma of no special type (NST). Given that most lobular breast cancers are ER+, in current clinical practice, newly diagnosed metastatic ILC (mILC) - either recurrent or de novo metastatic disease - is generally treated with sequential endocrine therapies (ET) until the tumor becomes endocrine resistant. ILC often presents as non-measurable disease on imaging, and it is often difficult to determine treatment response accurately using conventional imaging techniques. Therefore, novel ways of monitoring disease response are urgently needed. Analysis of circulating tumor DNA (ctDNA) offers an alternative, minimally invasive approach for monitoring treatment response, and can also identify molecular alterations that may predict resistance to endocrine therapies. Understanding early ctDNA dynamics during endocrine therapy is essential for future prospective clinical trials with adaptive molecularly driven designs. LBC-Monitor aims to define the optimal early timepoint of molecular response by ctDNA and the dynamics of these early changes as patients with mILC begin first line therapy with an antiestrogen agent such as an aromatase inhibitor or fulvestrant.

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

• Study Contact: Name: Kelsey Mitch, RN; Phone Number: 4126412357; Email: adamikka2@upmc.edu
• Study Contact Backup: Name: Lucia Borasso, BA; Phone Number: 4126413304; Email: borrlm@upmc.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • Magee Women's Hospital of UPMC
      • Principal Investigator: Julia Foldi, MD, PhD
      • Contact: Kelsey Mitch, RN; Phone Number: 4126412357; Email: adamikka2@upmc.edu
      • Contact: Lucia Borasso, BA; Phone Number: 4126413304; Email: borrlm@upmc.edu

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Patients must have histologically or cytologically confirmed invasive lobular breast cancer that is ER+ (> 1% staining) and HER2-negative as per ASCO/CAP guidelines with radiographical or clinical evidence of metastatic disease, who plan to begin first line endocrine therapy with an aromatase inhibitor or fulvestrant alone for 12 weeks.

Description

Inclusion Criteria:

1. Signed informed consent

2. Patients must have histologically or cytologically confirmed invasive lobular breast cancer that is ER+ (> 1% staining) and HER2-negative as per ASCO/CAP guidelines with radiographical or clinical evidence of metastatic disease

   1. Lobular histology as assessed on either tissue collected from a metastatic lesion or from the patient's primary breast tumor (in case of recurrent metastatic disease)
   2. Patients with mixed ductal/lobular (NST/ILC) tumors are eligible to participate (with the ultimate goal to evaluate 20 patients with pure ILC)
   3. Patients must have tumor tissue available for whole exome sequencing for Signatera assay design

3. Prior therapies:

   1. Patients must not have received any therapy in the metastatic setting
   2. Patients could have received adjuvant therapy as indicated for their primary breast cancer
4. Age ≥ 18 years
5. Patients may be pre- or post-menopausal.

Exclusion Criteria:

1. Stage I-III breast cancer
2. Lack of lobular histology on tumor tissue biopsy
3. Other active cancer (previously treated cancer with no current evidence of disease is allowed)
4. ctDNA assay development is unattainable due to insufficient tumor tissue or sequencing failure

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in ctDNA	Change in circulating tumor DNA (ctDNA) is measured by MTM/ml in patients receiving first line endocrine therapy (an aromatase inhibitor or fulvestrant) for metastatic lobular breast cancer.	Baseline, at 4 weeks, at 8 weeks, at 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	Length of time from start of treatment that patients live without disease progression per RECIST v1.1 in those with measurable disease on imaging. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). Data will be collected only in patients who completed the initial 12-week lead-in period with antiestrogen treatment.	Up to 2 years

Collaborators and Investigators

• Sponsor: Julia Foldi
• Investigators: Principal Investigator: Julia Foldi, MD, PhD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2024
• Primary Completion (Estimated): October 31, 2029
• Study Completion (Estimated): October 31, 2029

Study Registration Dates

• First Submitted: October 29, 2024
• First Submitted That Met QC Criteria: October 29, 2024
• First Posted (Actual): October 30, 2024

Study Record Updates

• Last Update Posted (Actual): January 20, 2026
• Last Update Submitted That Met QC Criteria: January 16, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: human epidermal growth factor receptor 2 (HER2); ctDNA (circulating tumor DNA); CDK4/6 inhibitors (CDK4/6i); endocrine therapies (ET); estrogen and progesterone receptor (ER and PR) positive
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Skin Diseases; Breast Diseases; Carcinoma; Neoplasms, Ductal, Lobular, and Medullary; Breast Neoplasms; Skin and Connective Tissue Diseases; Carcinoma, Lobular
• Other Study ID Numbers: HCC 24-096

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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