使用mDETECT检测监测转移性乳腺癌患者的治疗应答

Metastatic breast cancer treatment response is currently monitored with CT-scans every 3-6 months leaving many patients on ineffective therapy while their disease progresses. We have developed the methylation DETEction of Circulating Tumour DNA (mDETECT) assay, a targeted DNA methylation-based Next Generation Sequencing liquid biopsy designed to detect cancer specific DNA methylation patterns. The breast cancer assay targets 60 hypermethylated regions (>400 CpGs), detects all subtypes of breast cancer, is quantitative for molecules of methylated DNA, and shows 93% sensitivity at 100% specificity for TNBC with a limit of detection of 0.025%. It is both tumour and treatment agnostic as well as being compact (2 million sequencing reads per sample) making it ideal for frequent disease monitoring. We are conducting a prospective multi-centre observational cohort study to monitor metastatic breast cancer patients using the mDETECT liquid biopsy as they undergo treatment. Metastatic breast cancer patients are eligible regardless of subtype or treatment and are followed through treatment changes. 20mL of blood is collected at each standard of care blood draw for up to 3 years. Patients are assessed for response to treatment and monitored for disease progression. Over 120 participants have been enrolled to date with recruitment ongoing, generating over 500 timepoints (0-22 timepoints/patient). Initial patients with completed longitudinal timepoints have been assessed using the mDETECT assay. Although complete clinical and radiological outcome data are not yet available, early molecular results show decreasing mDETECT levels during treatment and increasing levels prior to treatment change or disease progression. These preliminary findings demonstrate the potential of methylation-based monitoring for metastatic breast cancer patients, a key clinical need as there are many therapy options available and complex treatment sequence decisions to be made. We will evaluate whether specific mDETECT trajectories predict disease progression and durable treatment response. Ongoing follow-up and integration of radiology data will further assess the predictive value of mDETECT in monitoring metastatic breast cancer. The mDETECT assay may allow for more timely treatment decision-making in metastatic breast cancer, improving outcomes and reducing prolonged exposure to ineffective therapy.