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I-SPY 2 Publication in Nature Communications Shows Signatera™ Can Predict Treatment Response and Recurrence Risk in Early-Stage Breast Cancer
Latest findings from multicenter trial demonstrate Signatera’s ability to improve risk stratification for patients with therapy-resistant disease AUSTIN,
About this update from Natera, Inc.
[{"type":"text","content":"\nLatest findings from multicenter trial demonstrate Signatera’s ability to improve risk stratification for patients with therapy-resistant disease\n\n AUSTIN, Texas--(BUSINESS WIRE)--\nNatera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA and precision medicine, together with Quantum Leap Healthcare Collaborative, today announced the publication of new findings from the I-SPY 2 trial in Nature Communications.\n\nThe study examined how Signatera can refine risk assessment in patients with early-stage breast cancer whose tumors resist neoadjuvant therapy (NAT). These cancers often leave behind substantial residual disease and carry a higher risk of metastasis, though only about 15–30% recur within three years1-3. Distinguishing which NAT-resistant tumors are more likely to recur could guide treatment decisions to potentially prevent or delay metastatic recurrence.\n\nResearchers used Signatera to measure personalized circulating tumor DNA (ctDNA) in 723 women with high-risk, early-stage breast cancer receiving NAT at four time points: 1) before treatment; 2) after three weeks of paclitaxel with or without an investigational agent; 3) between paclitaxel- and anthracycline-based regimens; and 4) after completing neoadjuvant therapy. Key findings include:\n\n\nSignatera ctDNA testing improved prognostic precision beyond residual cancer burden (RCB) alone in patients with high RCB (RCB-II/III) following neoadjuvant therapy (NAT).\n\n\nSignatera-negative patients, at either pretreatment or post-NAT, had a much lower risk of metastasis:\n\n\nRCB-II: Post-NAT, pre-surgery (T3) 3-year DRFS = 88% (ctDNA–) vs. 57% (ctDNA+), adj HR = 0.29, p = 0.001\n\n\nRCB-III: Post-NAT, pre-surgery (T3) 3-year DRFS = 83% (ctDNA–) vs. 22% (ctDNA+), adj HR = 0.14, p \n\n\n\nPersistent Signatera positivity post-NAT (T3) was a strong independent predictor of metastatic recurrence (adj HR = 5.20, p \n\n\n\n\nEarly Signatera ctDNA clearance at week 3 (T1) was strongly associated with favorable response to NAT, including regimens containing immune checkpoint inhibitors and HER2-targeted therapies, supporting its potential as an early, dynamic biomarker of treatment sensitivity.\n\n\n\nPersonalized Signatera assay variants remained highly stable despite tumor evolution, with median conservation rates of 94–97% between pretreatment and post-NAT tumor samp...