Clinical trial NCT05914792: Longitudinal ctDNA Surveillance for Older Women With ER+ Breast Cancer Who Omit Surgery
Official title: Longitudinal ctDNA Monitoring in Older Women With ER+ Breast Cancer Who Forego Upfront Surgery in Favor of Primary Endocrine Therapy
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Breast Cancer
Keywords: estrogen receptor positive (ER+)
progesterone receptor (PR+)
early-stage breast cancer
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Natera, Inc.
First posted: 2023-06-22
Enrollment: 49
Sex: FEMALE
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of ctDNA positivity
timeFrame: Up to 5 years
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Up to 5 years
measure: Breast cancer-specific survival (BCSS)
timeFrame: Up to 5 years
measure: Overall survival (OS)
timeFrame: Up to 5 years
measure: 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)
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: UPMC Magee Womens Hospital - Surgical Oncology
state: Pennsylvania
Study officials:
affiliation: UPMC Magee Women's Hospital, UPMC Hillman Cancer Center
name: Priscilla McAuliffe, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: