Signatera Test Performance in Invasive Lobular Carcinoma with Supraclavicular Metastases
Yes, the Signatera test can detect invasive lobular carcinoma that has metastasized to supraclavicular lymph nodes, with a patient-level sensitivity of 88.2% for detecting recurrent disease, though a negative test does not definitively rule out metastatic disease. 1, 2
Detection Capability for Metastatic ILC
The Signatera assay demonstrated feasibility and clinical utility specifically in metastatic invasive lobular carcinoma patients:
In a real-world cohort of 66 patients with metastatic ILC, serial ctDNA testing using Signatera successfully monitored disease status across 355 plasma samples, demonstrating that the test can detect circulating tumor DNA from ILC regardless of metastatic site 1
The personalized, tumor-informed approach works by sequencing the primary tumor and tracking up to 16 patient-specific variants, making it applicable to ILC's unique molecular profile including E-cadherin loss and other distinctive mutations 1, 3
Supraclavicular lymph node involvement represents N3c disease in breast cancer staging, indicating advanced regional disease that would be expected to shed detectable ctDNA into circulation 4, 5
Accuracy of a Negative Signatera Test
A negative Signatera test provides strong but not absolute reassurance:
Negative Predictive Value
A negative ctDNA result was associated with 97% overall survival at 6 months and approximately 90% survival at 12 months in the metastatic ILC cohort 1
In the long-term follow-up study of 156 breast cancer patients, those with serially negative ctDNA tests had superior clinical outcomes and remained disease-free during extended monitoring 2
Sensitivity Limitations (False Negative Rate)
The patient-level sensitivity for detecting relapse was 88.2%, meaning approximately 12% of patients who relapsed had negative ctDNA tests before clinical detection of recurrence 2
All four patients with false-negative tests before relapse had hormone receptor-positive (HR+) disease, suggesting that HR+ tumors (which comprise 80% of ILC cases) may have lower ctDNA shedding rates 3, 2
Five of 122 non-relapsed patients had occasional positive tests (all HR+), indicating the need for serial monitoring rather than relying on a single test result 2
Clinical Implications for Monitoring
Serial testing provides superior prognostic information compared to single timepoint assessment:
In patients on treatment for metastatic ILC, 92% (11/12) of those with either decreasing or stable ctDNA levels showed clinical benefit, while only 31% (4/13) with rising ctDNA had clinical benefit on imaging 1
The positive predictive value of ctDNA testing increased exponentially with each consecutive positive result, emphasizing the importance of longitudinal monitoring 1
For patients with known supraclavicular involvement (N3c disease), serial ctDNA monitoring could detect progression or treatment response months before conventional imaging 1, 2
Important Caveats for ILC
Invasive lobular carcinoma presents unique detection challenges that may affect ctDNA testing:
ILC has distinctive metastatic patterns, spreading to unusual sites including serosa, meninges, and ovaries, and is notoriously difficult to detect on imaging due to its infiltrative growth pattern 3, 6
The false-negative rate on mammography for ILC is 19%, with 46% showing no evidence of tumor even in retrospect, suggesting that ILC's low-opacity, single-cell infiltrative pattern may also result in lower ctDNA shedding 7
ILC demonstrates multifocality and multicentricity at presentation, and 44% of patients have axillary lymph node metastases at diagnosis, indicating aggressive biology despite often favorable receptor profiles 6, 7
Practical Recommendation
For a patient with history of ILC and suspected supraclavicular involvement:
A positive Signatera test strongly supports the presence of metastatic disease and warrants immediate clinical action including tissue biopsy for confirmation and treatment planning 1
A negative Signatera test does NOT exclude metastatic disease, particularly in HR+ ILC, and tissue sampling of the supraclavicular node remains essential for definitive diagnosis 2
If metastatic ILC is confirmed, serial ctDNA monitoring every 1-3 months can provide real-time assessment of treatment response superior to imaging alone 1
Given the 12% false-negative rate, clinical suspicion based on imaging or physical examination should always supersede a negative ctDNA result 2