Natera Inc, San Carlos, Calif, has announced the publication of clinical study results demonstrating that the Signatera molecular residual disease (MRD) assay detected disease relapse up to 2 years earlier than imaging in patients with early-stage breast cancer.1

Signatera is the first circulating tumor DNA (ctDNA) test custom built for monitoring molecular treatment and assessing MRD. The recent study publication validates clinical performance of Signatera for recurrence monitoring and MRD assessment in breast cancer. The test is available for research use only (RUO) until its planned clinical launch in 2019.

The Signatera methodology differs from that of currently available liquid biopsy tests, which test for a fixed panel of therapeutically relevant genes. Signatera provides each individual with a customized blood test tailored to match the clonal mutations found in that individual’s tumor tissue. This procedure maximizes accuracy for detecting the presence or absence of MRD in a blood sample, even at levels down to a single mutant molecule in a tube of blood. Signatera also enables researchers to track up to several hundred additional mutations of interest, for clinical studies.

Aleshin

Alexey Aleshin, MD, MBA, Natera.

Breast cancer is the second leading cause of cancer death among women.2 Approximately 250,000 women are diagnosed with invasive breast cancer every year in the United States, and it is estimated that 2 million cases are diagnosed worldwide.2,3 While the overall survival rate for breast cancer has improved, recurrence is an ongoing problem, with 5-year recurrence rates estimated to be as high as 30%.4,5

The prospective study funded by Cancer Research UK evaluated 49 patients with early-stage breast cancer who had recently completed treatment with surgery and adjuvant chemotherapy at one of three National Health Service trusts in the UK (Christie Foundation, Imperial College Healthcare, and University Hospitals of Leicester). The study included a cross-section of breast cancer subtypes, including HER2-positive, hormone receptor-positive, and triple-negative subtypes. Plasma samples were collected every 6 months for up to 4 years from each patient. A total of 208 plasma samples were then analyzed using Signatera, and results were correlated with radiographic imaging and clinical outcomes.

In the study, Signatera detected 16 of 18 relapses (89%), with a median lead time 8.9 months earlier than the current standard of care. Among the 31 patients who did not relapse, Signatera reported zero false positives across 156 plasma samples tested, with an overall specificity of 100%, representing a positive predictive value of 100%.

The study concluded that early recurrence detection with Signatera may provide a critical window of opportunity for additional therapeutic intervention. Furthermore, tumor analysis showed that 33% of all patients had no actionable hotspot mutations, indicating the validity of Signatera’s personalized, tumor-informed approach to ctDNA monitoring.

Coombes

R. Charles Coombes, MD, PhD, Imperial College London.

“The study showed that Signatera is an effective tool for the early detection of breast cancer recurrence, which occurs in up to 30% of certain patient groups,” says Alexey Aleshin, MD, MBA, oncology medical director at Natera. “With imaging and serum-based biomarkers alone, recurrence is often caught late—after patients become symptomatic. We now have an accurate tool for detecting molecular recurrence and hope this will accelerate future research into evaluating whether treatment can be delivered earlier.”

“Standard technologies for the detection of cancer recurrence have always been imprecise,” says R. Charles Coombes, MD, PhD, professor of medical oncology and head of the cancer research center at Imperial College London. “With this innovative method of detecting minimal residual breast cancer, we now have the opportunity to conduct trials of treatments to prevent patients relapsing with symptomatic metastatic breast cancer.”

For further information, visit Natera.

References

  1. Coombes C, Page K, Salari R, et al. Personalized detection of circulating tumor DNA antedates breast cancer metastatic recurrence. Clinical Cancer Research. Epub before print, April 16, 2019; doi: 10.1158/1078-0432.CCR-18-3663.
  1. About breast cancer [online]. Atlanta: American Cancer Society, 2019. Available at: www.cancer.org/cancer/breast-cancer/about.html. Accessed June 3, 2019.
  1. Breast cancer statistics [online]. London: World Cancer Research Fund, 2019. Available at: www.wcrf.org/dietandcancer/cancer-trends/breast-cancer-statistics. Accessed June 3, 2019.
  1. Brewster AM, Hortobagyi GN, Broglio KR, et al. Residual risk of breast cancer recurrence 5 years after adjuvant therapy. J Natl Cancer Inst. 2008;100(16):1179–1183; doi: 10.1093/jnci/djn233.
  1. Dent R, Trudeau M, Pritchard KI, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007;13(15 pt. 1):4429–4434; doi: 10.1158/1078-0432.CCR-06-3045.