Personalised Disease Monitoring in Metastatic Breast Cancer (PDM-MBC)

Personalised Disease Monitoring During Treatment With an Aromatase Inhibitor + Cyclin Dependent Kinase (CDK) 4/6 Inhibitor as 1st Line Endocrine Therapy in Patients With ER-positive/HER2-negative Metastatic Breast Cancer

Patients with metastatic breast cancer may respond well to treatment and metastases can remain stable for several years. Despite personalised medicine being increasingly used for diagnosis and treatment, follow-up still include radiological response evaluation every 3-4 months, which renders a significant number of 'unnecessary' exams for patients with long-term stable disease. Increasing evidence indicates that tumour markers such as circulating tumour DNA (ctDNA), thymidine kinase 1 (TK1) and cancer antigen 15-3 (CA15-3) may be useful for disease monitoring in the metastatic setting. However, algorithms that accurately define the time-points at which imaging can be foregone or reinstituted when progression is forecast, have not been developed. This study will measure ctDNA, TK1 and CA15-3 at all imaging time-points. The primary aim is to develop an algorithm based on these biomarkers, alone or in combination, that with sufficient specificity and sensitivity can advise whether a scan can be safely omitted at a specific time-point, for patients with MBC receiving first line therapy with AI plus cyclin dependent kinase 4/6 inhibitor (CDK4/6i). Additional samples will be stored such that novel biomarkers can also be tested in future. The cost-effectiveness of using the devised biomarker protocol will be evaluated.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer Metastatic; Estrogen Receptor-positive Breast Cancer

Detailed Description

One hundred patients with estrogen receptor positive (ER+)/ Human epidermal growth factor receptor negative (HER2-) metastatic or locally advanced breast cancer, eligible for 1st line endocrine therapy with AI + CDK4/6i will be included. Patients will receive standard therapy (AI + CDK4/6i) and follow-up will proceed according to local guidelines, namely cross sectional imaging with CT thorax/abdomen/pelvis +/- MRI as required and analysis of CA 15-3, every 3 cycles for the first year and every 3-4 cycles thereafter. Participation in the study will include serial blood sampling for the bespoke study biomarkers. Decisions on progression will be made according to the routine imaging tests and the biomarkers will be subsequently analysed.

The investigators hypothesise that the biomarkers ctDNA, TK1 and CA15-3, alone or in combination, will accurately correlate with disease status in patients receiving AI + CDK4/6i for metastatic breast cancer such that routine imaging can be delayed until predefined levels of biomarker progression.

Primary aim: To develop a biomarker-based prediction model to be used in patients with metastatic breast cancer, receiving first line therapy with AI and CDK4/6i, that provides the physician with a recommendation whether or not a radiological examination is required, based on the likelihood that the scan will actually show progressive disease.

Secondary aims

• To define the lead time between rising biomarker and subsequent progression on imaging
• To define the clinical utility of the bespoke biomarkers for disease monitoring
• The relative value of analysing TK1 "on CDK4/6i treatment" versus "off CDK4/6i treatment" for disease monitoring
• To define the economic impact of implementation of the chosen prediction model

• Study Type: Observational
• Enrollment (Actual): 97

Contacts and Locations

Study Locations

• Sweden
  • Gothenburg, Sweden
    • Department of Oncology, Sahlgrenska University Hospital
  • Jönköping, Sweden
    • Department of Oncology, Ryhov Hospital
  • Kalmar, Sweden
    • Department of Oncology, Kalmar Hospital
  • Linköping, Sweden
    • Department of Oncology, Linköping University Hospital
  • Stockholm, Sweden
    • Department of Oncology, Södersjukhuset
• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
  • Wigan, United Kingdom
    • Wigan Infirmary, Wrightington, Wigan and Leigh NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with ER+/HER2- metastatic or locally advanced breast cancer, not amendable for curative surgery, eligible for 1st line endocrine therapy with aromatase inhibitor (AI) + CDK4/6-inhibitor (CDK4/6i).

Description

Inclusion Criteria:

• Confirmed metastatic breast cancer (stage 4) or locally advanced disease not amendable to curative resection. Patients who have locoregional disease only an in whom a response to therapy would lead to potentially curative resection are not eligible.
• ER+/HER2- breast cancer (assessed locally). NOTE: If immunohistochemical analysis is not available from metastatic tissue, the ER and HER2 status from the primary tumour should be used.
• For patients who have had a prior non-breast malignancy within the last 5 years (excluding in situ carcinoma of the cervix and basal cell carcinoma of the skin) biopsy of a metastatic site is required to confirm the diagnosis of metastatic ER+/HER2- breast cancer.
• Eligible for 1st line endocrine treatment with AI + CDK4/6-inhibitor according to local guidelines.

NOTE: ≥ 12 month since termination of adjuvant AI if used NOTE: Patients may have received one prior line of chemotherapy for metastatic breast cancer but should have disease progression at study entry.

• Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2 (Oken 1982).
• Life expectancy >3 months.
• Age ≥ 18 years
• Metastatic disease must be radiologically assessable, by means of at least one of the following techniques: computerised tomography (CT) and/or magnetic resonance imaging (MRI), i.e. lesions can be measurable or non-measurable according to RECIST 1.1, but must be clearly evaluable according to the radiologist and/or treating physician. Patients with bone predominant disease who lack evaluable disease on CT according to RECIST 1.1.

must have serial MRI including the representative area in addition to CT TAP. NOTE: Previously irradiated lesions are deemed measurable only if progression is documented at the site after completion of radiation.

- Willing and able to provide informed consent to undergo all trial procedures.

Exclusion Criteria:

• Known CNS metastases, carcinomatous meningitis or leptomeningeal disease unless treated with radiotherapy and symptomatically stable at least 2 weeks after discontinuation of steroids. For such patients, ongoing monitoring of CNS disease is required as standard of care. No screening is needed for asymptomatic patients.
• Concurrent disease(s) or familial, sociological or geographical condition that would, in the investigator's opinion, preclude compliance with study procedures.
• Any serious medical disorder that would compromise the patient's safety.
• Dementia altered mental status, or any psychiatric condition that would prevent the understanding or rendering of Informed Consent.

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in blood levels of ctDNA, CA15-3 and TK-1 assays from baseline to disease progression	ctDNA, CA15-3 and TK-1 assays will be performed at baseline, 2 weeks and at every imaging timepoint to develop a statistical algorithm to predict disease progression that can be tested prospectively in future studies.	3-5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best time for TK1 analysis during CDK4/6i treatment ("on treatment" vs "off treatment")	The relative value of analysing TK1 "on CDK4/6i treatment" versus "off CDK4/6i treatment" for disease monitoring	3-5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The economic impact of implementation of the chosen prediction model	Cost effectiveness analysis of using the prediction model	3-5 years

Collaborators and Investigators

• Sponsor: The Christie NHS Foundation Trust
• Collaborators: Sahlgrenska University Hospital
• Investigators: Principal Investigator: Dr Sacha Howell, MD, PhD, University of Manchester and The Christie NHS Foundation Trust; Principal Investigator: Maria Ekholm, MD, PhD, University of Gothenburg and Region Jönköping

Publications and helpful links

General Publications

• Mouhanna P, Stahlberg A, Andersson D, Albu-Kareem A, Elinder E, Eriksson O, Kavanagh A, Kovacs A, Larsson KF, Linderholm B, Uminska M, Osterlund T, Howell SJ, Ekholm M. Integration of personalised ultrasensitive ctDNA monitoring of patients with metastatic breast cancer to reduce imaging requirements. Int J Cancer. 2025 Apr 15;156(8):1509-1517. doi: 10.1002/ijc.35292. Epub 2024 Dec 18.

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2019
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): January 31, 2030

Study Registration Dates

• First Submitted: July 8, 2019
• First Submitted That Met QC Criteria: October 20, 2020
• First Posted (Actual): October 22, 2020

Study Record Updates

• Last Update Posted (Estimated): December 2, 2025
• Last Update Submitted That Met QC Criteria: November 25, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Breast Neoplasms; Precision Medicine; Circulating Tumor DNA; Neoplasm Metastasis; disease monitoring; Biomarkers, Tumor; Thymidine Kinase
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplastic Processes; Skin Diseases; Breast Diseases; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Neoplasms; Breast Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: CTFSp161

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: No