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Thanks to improvements in early detection and personalized treatment, people with breast cancer experience better outcomes than ever before.1 However, identifying and monitoring patients at high risk of recurrence remains a major challenge. Up to 30% of breast cancer patients who don’t show evidence of residual disease after treatment will eventually have a metastatic relapse.2-3

Improving outcomes for these patients depends on finding molecular residual disease (MRD) 一 trace amounts of cancer that persist after treatment or emerge in early recurrence. The current standards for monitoring patients after curative treatment are routine history, physical exams, and annual mammography.4 However, these methods do not always catch signs of early breast cancer recurrence.5

There remains an unmet need for an accurate, noninvasive, and individualized tool to help oncologists monitor and predict recurrence for their highest risk patients.6

Detecting MRD with circulating tumor DNA

Over the last decade, circulating tumor DNA (ctDNA) has emerged as a sensitive biomarker for detecting and monitoring MRD. During the natural cell death process, tumor cells release small fragments of DNA into the bloodstream, where it can be measured noninvasively with a blood draw.

If a patient with breast cancer tests positive for MRD after primary treatment, this can be an early sign of micrometastatic recurrence.7 Testing negative for MRD, on the other hand, can  reassure them that the risk of recurrence is low.

For surveillance of high risk breast cancer and other solid tumors, ctDNA offers:

  • Dynamic visualization: Thanks to ctDNA’s relatively short half-life, changes in ctDNA levels reflect real-time changes in MRD better than other biomarkers or imaging8
  • Clarity for indeterminate findings: When other indicators are unavailable or ambiguous, ctDNA levels provide additional information to support clinical decisions
  • Noninvasive assessment: Blood draws are safe and convenient for most patients

The most common use of ctDNA today is in liquid biopsies that identify actionable mutations to help guide therapy selection. However, some commercial liquid biopsy assays use the same fixed gene panel of predetermined cancer-associated mutations to try to monitor for recurrence. This approach is limited because it relies on a patient’s tumor having those specific mutations. For these patients, non-personalized liquid biopsies offer limited sensitivity and specificity.8

Personalized surveillance

To meet the need for a more sensitive ctDNA assay, Natera, a global leader in cell-free DNA testing, developed Signatera™, a personalized tumor-informed ctDNA test optimized for serial surveillance monitoring.

Unlike fixed-panel liquid biopsies, Signatera is custom built for each patient using a small tumor tissue sample. More than 20,000 genes from each patient’s tumor are analyzed with next-generation sequencing to define the tumor’s unique mutation signature. Signatera helps oncologists to monitor patients who otherwise might be excluded from assays that rely on fixed gene panels to find ctDNA.

After the assay is designed, Signatera requires only simple blood draws to detect and measure a patient’s ctDNA levels.

Detecting recurrence up to 2 years ahead of conventional indicators3

Signatera has been clinically validated for recurrence monitoring and MRD assessment in high risk breast cancer. In a study published in Clinical Cancer Research, a cohort of patients from the Exploratory Breast Lead Interval Study (EBLIS) trial with a range of high risk breast cancer subtypes (HR+/HER2-, HR+/HER2+, and TNBC) were evaluated after surgery and adjuvant therapy to determine the lead interval between ctDNA detection and clinical metastatic disease.

Blood samples were collected every six months for four years. Patients also received standard screening procedures, including CT scans and blood testing for other biomarkers or signs of cancer recurrence.

Results indicated that Signatera detected breast cancer recurrence far earlier than imaging or other biomarkers:

  • Up to 2 years earlier
  • A median of 8.9 months ahead of clinical recurrence

The study also found that Signatera demonstrated:

  • 89% sensitivity: Signatera detected plasma ctDNA in 16 out of 18 patients prior to clinical or radiographic relapse
  • 100% specificity: None of the 31 non-relapsing patients were ctDNA positive during the course of the study

The future of high risk breast cancer testing is personal

For patients with high risk breast cancer, Signatera’s tumor-informed ctDNA assay can be paired with traditional monitoring tools to catch recurrence earlier during surveillance, even before clinical relapse.

Signatera’s potential as a personalized test reaches beyond recurrence detection for high risk breast cancer. Signatera has also been shown to assess post-surgical recurrence risk when used serially during neoadjuvant chemotherapy.9

For patients with metastatic breast cancer, Signatera can help oncologists learn whether a patient is responding to immunotherapy as early as 6 weeks into treatment.10 As a result, the Centers for Medicare & Medicaid Services has granted coverage for Signatera for immunotherapy monitoring for all solid tumors, including breast cancer.

Additional prospective trials are underway to validate Signatera for guiding adjuvant chemotherapy decisions in patients with breast cancer.

For more information, click here.


Signatera has been developed and its performance characteristics determined by the CLIA-certified laboratory performing the test. The test has not been cleared or approved by the US Food and Drug Administration (FDA). CAP accredited, ISO 13485 certified, and CLIA certified. © 2022 Natera, Inc. All Rights Reserved.


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