Longitudinal ctDNA Surveillance for Older Women With ER+ Breast Cancer Who Omit Surgery

Longitudinal ctDNA Monitoring in Older Women With ER+ Breast Cancer Who Forego Upfront Surgery in Favor of Primary Endocrine Therapy

This prospective study recruits patients with ER+/HER2-, non-metastatic breast cancer who omit upfront surgery in favor of primary endocrine therapy for sample collection and prospective circulating tumor DNA (ctDNA) measurement to guide disease surveillance.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer

Detailed Description

Age is one of the most important risk factors for the development of breast cancer. Nearly a third of all breast cancer cases occur in older women (aged ≥ 70 years), with most cases being estrogen receptor-positive (ER+). Such tumours are unlikely to be the ultimate cause of death for older women, particularly when considering other comorbidities. Our group has recently shown that risk of breast cancer-related mortality is only around 3% for older women who forego upfront surgery and instead treated with primary endocrine monotherapy. However, with omission of surgery, surveillance for tumor growth or treatment failure is important but requires patients (and their caregivers) to have regular imaging and to see their oncology team every 3 months, which can be quite burdensome. Thus, this study employs a ctDNA surveillance scheme to monitor for potential tumor growth. Partnering with Natera, this study uses a bespoke, tumor-specific ctDNA assay (Signatera) to monitor for changes in ctDNA dynamics while the patient is on endocrine therapy.

This study is for patients who choose not to undergo primary surgical intervention and are managed medically on primary endocrine therapy (any endocrine therapy permitted). Patients will undergo Signatera testing at the time of regularly scheduled clinic follow-up visits and/or at the time of surveillance imaging, which will occur every 3-6 months. Patients will also be asked to complete regular surveys while participating in the study.

• Study Type: Observational
• Enrollment (Actual): 49

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Magee Womens Hospital - Surgical Oncology

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Women 70 years of age or older with ER+/HER2-, non-metastatic breast cancer who forego upfront surgery in favor of primary endocrine therapy.

Description

Inclusion Criteria:

• early-stage (stages I-III) breast cancer
• estrogen receptor positive (ER+) and/or progesterone receptor positive (PR+) and HER2 receptor negative
• able to provide blood samples
• decision made by treating physician and patient to forego upfront surgery in favor of medical management with endocrine therapy
• non-metastatic disease at diagnosis (patients need not have staging scans; patients at higher risk for de novo stage IV disease should not have any symptoms concerning for metastatic disease)
• patients may be taking any endocrine therapy
• patients may be taking any CDK4/6 inhibitor as deemed necessary by their treating physician
• any ECOG Performance Status allowed
• if patients have synchronous bilateral ER+ breast cancer, tissue from both sites should be submitted to Natera to perform ctDNA testing
• patients with multifocal/multicentric tumors are eligible and the largest focus of cancer should be submitted for testing

Exclusion Criteria:

• under 70 years of age
• breast cancer that is not estrogen receptor positive (ER+) or progesterone receptor (PR+)
• unable to provide blood samples or insufficient tumor tissue for Signatera testing

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of ctDNA positivity	Proportion of patients with ER+/HER2- breast cancer who omit upfront surgery in favor of primary endocrine therapy who have any ctDNA positivity using Signatera assay.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	The length of time after treatment initiation that patient is alive and without any evidence of tumor progression as defined by RECIST1.1 criteria. Per RECISIT v1.1: Progressive Disease (PD): ≥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). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.	Up to 5 years
Breast cancer-specific survival (BCSS)	BCSS is defined as the length of time from the date of diagnosis through the end of follow up that patients are free from breast cancer-related mortality.	Up to 5 years
Overall survival (OS)	The length of time from the date of diagnosis through the end of follow up that patients are still alive.	Up to 5 years
Longitudinal quality of life assessment using National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Breast Cancer Symptom Index - 16 Item Version (NCCN NFBSI-16)	This assessment is a 16 item questionnaire using Likert scale (0-4) measured with each ctDNA blood draw. Score ranges from 0-64 with higher scores indicative of higher quality of life / asymptomatic from cancer-related therapy.	Up to 5 years

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Collaborators: Natera, Inc.
• Investigators: Principal Investigator: Priscilla McAuliffe, MD, PhD, UPMC Magee Women's Hospital, UPMC Hillman Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2022
• Primary Completion (Actual): October 16, 2024
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: June 13, 2023
• First Submitted That Met QC Criteria: June 13, 2023
• First Posted (Actual): June 22, 2023

Study Record Updates

• Last Update Posted (Actual): April 10, 2025
• Last Update Submitted That Met QC Criteria: April 7, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: estrogen receptor positive (ER+); early-stage breast cancer; progesterone receptor (PR+)
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: HCC 22-088; STUDY21100091 (Other Identifier: University of Pittsburgh)

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: No
• product manufactured in and exported from the U.S.: No