MRD ctDNA Surveillance for Breast Cancer Recurrence
The Centers for Medicare & Medicaid Services has determined that Signatera’s molecular residual disease (MRD) test designed to detect circulating tumor DNA, or ctDNA, has met coverage requirements for adjuvant and recurrence monitoring in patients with stage IIb or higher breast cancer. Medicare’s coverage applies across all breast cancer subtypes including HR-positive, HER2-positive, and triple-negative breast (TNBC) cancers.
CancerConnect Breast Cancer Support Community
About ctDNA
Cancer is caused by genetic mutations, and these mutations can be detected by measuring circulating tumor DNA, or ctDNA, in the blood. Detection of ctDNA allows for personalized cancer surveillance based on an individual’s unique set of cancer mutations.
Circulating tumor DNA is 150–200-base-pair fragments of DNA, which originate from cancer cells and are present in the bloodstream or other body fluids. ctDNA is different than cell-free DNA (cfDNA) which is ALL the DNA in the bloodstream including germline DNA and tumor DNA. ctDNA is the portion of cfDNA that is derived specifically from the cancer.
As many as 30% of early-stage breast cancers recur and recurrence surveillance currently relies on imaging techniques like computerized tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). These imaging tools are limited in their ability to detect MRD - ctDNA can be detected in the blood long before it appears on a CT or MRI scan and has the potential to change how breast cancer is managed.
How is ctDNA used for the management of early-stage cancers?
Across all stages of surgically removed cancer, detection of ctDNA following surgery is a strong predictor of cancer recurrence. For example, measurement of ctDNA is performed routinely in early-stage colon cancer and helps clinicians decide when to intensify therapy in certain situations, and conversely, the absence of ctDNA can provide an opportunity to minimize surveillance or avoid adjuvant treatment. In breast cancer the most immediate application of ctDNA is monitoring for the early detection of cancer recurrence and immunotherapy monitoring.
Zenocutuzumab - the first approved systemic therapy for patients with NRG1 fusion–positive NSCLC or pancreatic adenocarcinoma.
Zenocutuzumab targeted therapy approved for treatment of pancreatic ductal adenocarcinoma and non-small cell lung cancer with NRG1 fusions.
Immunotherapy After Chemoradiotherapy Promising in Limited-Stage Small Cell Lung Cancer
Adjuvant therapy with Imfinzi (durvalumab) significantly improved survival outcomes for patients with limited-stage SCLC
Breakthrough in Understanding Tamoxifen's Effectiveness in Breast Cancer: Gut Bacteria Play a Crucial Role
Since tamoxifen is taken orally and travels through the digestive system, variations in patient responses may be connected to the gut microbiome—the trillions of bacteria in our intestines that differ significantly from one person to another.
Persistent ctDNA Correlates With Disease Recurrence in Early Breast Cancer
Persistent detection of ctDNA with the SignateraTM assay was associated with a 100% risk of disease recurrence in patients with hormone receptor (HR)–positive, HER2-negative, node-positive, high-risk early breast cancer following treatment with adjuvant Verzenio and endocrine therapy, according to an analysis of data from the phase 3 monarchE trial presented at the 2023 San Antonio Breast Cancer Symposium.7
The role of ctDNA in cancer management is evolving and can help with treatment decisions, and planning. The ctDNA assay is best performed on the initial biopsy or surgical sample-patients should discuss the role of testing with their breast surgeon and consider ordering the test along with OncotypeDx and other decision aids.
About Signatera
Signatera is a custom-built ctDNA test for treatment monitoring and molecular residual disease (MRD) assessment in patients diagnosed with cancer. The Signatera test is personalized and tumor-informed, providing each individual with a customized blood test tailored to fit the unique signature of clonal mutations found in that individual’s tumor. Signatera is intended to detect and quantify cancer left in the body, at levels down to a single tumor molecule in a tube of blood.
Medicare’s coverage decision was primarily based on evidence from the Exploratory Breast Lead Interval Study, which demonstrated that Signatera could identify relapse with 89 percent sensitivity, 100 percent specificity, and a diagnostic lead time of up to two years ahead of radiographic imaging.
Breast Cancer Newsletter
References
- Coombes RC, Page K, Salari R, et al. Personalized detection of circulating tumor DNA antedates breast cancer metastatic recurrence. Clin Cancer Res. 2019;25(14):4255-426.
- Breast Cancer Facts and Statistics. Breastcancer.org. https://www.breastcancer.org/facts-statistics. Last updated on January 18, 2023.
- Tesarova P. Specific Aspects of Breast Cancer Therapy of Elderly Women. Biomed Res Int. 2016;2016:1381695.
- Lee JH, Menzies AM, Carlino MS, et al. Longitudinal monitoring of ctDNA in patients with melanoma and brain metastases treated with immune checkpoint inhibitors. Clin Cancer Res. 2020;26:4064-4071.
- Natera, Inc. BESPOKE Study of ctDNA Guided Immunotherapy. https://www.clinicaltrials. gov/ct2/show/NCT04761783
- https://www.natera.com/company/news/medicare-extends-coverage-of-nateras-signatera-mrd-test-to-breast-cancer
- Loi S, Johnston S, Arteaga C, et al. Results from a pilot study exploring ctDNA detection using a tumor-informed assay in the monarchE trial of adjuvant abemaciclib with endocrine therapy in HR+, HER2-, node-positive, high-risk early breast cancer. Presented at the 2023 San Antonio Breast Cancer Symposium; San Antonio, TX; December 5-8, 2023. PS06-01.
