Chien, Jo
Mayo Clinic
Division of Hematology/Oncology, University of California San Francisco, San Francisco, CA.
Citations 1
Immune Subtyping Identifies Patients With Hormone Receptor–Positive Early-Stage Breast Cancer Who Respond to Neoadjuvant Immunotherapy (IO): Results From Five IO Arms of the I-SPY2 Trial
Wolf, Denise M. , Yau, Christina , Glas, Annuska M. , Barcaru, Andrei, Kuilman, Midas M. , Swigart, Lamorna Brown , Hirst, Gillian L. , Basu, A. , Magbanua, Mark Jesus M. , Sayaman, Rosalyn W. , Huppert, Laura A. , Investigators, I-SPY2, Borowsky, Alexander D. , Pohlmann, Paula R. , Clark, Amy S. , Yee, Douglas , Perlmutter, Jane , Petricoin, Emanuel F. , Chien, A. Jo , Stringer-Reasor, Erica , Liu, Minetta C. , Nanda, Rita , Veer, Laura van ‘t , Melisko, Michelle , Albain, Kathy S. , Robinson, Patricia A. , Lo, Simon S. , Potter, David J. , Beckwith, Heather , Haddad, Tufia C. , Kemmer, Kathleen, Lu, Janice , Williams, Nicole , Ellis, Erin D. , Sanford, Amy, Sanft, Tara, Viscusi, Rebecca K., Arora, Mili, Northfelt, Donald W. , Haley, Barbara , Yung, Rachel L. , Mayer, Ingrid, Khan, Qamar J. , Edmiston, Kirsten K., Glas, Annuska , Mittempergher, Lorenza , Brown-Swigart, Lamorna , Hirst, Gillian L , Basu, Amrita , Magbanua, Mark J M , Sayaman, Rosalyn , Huppert, Laura , Delson, Amy , Symmans, W Fraser , Pohlmann, Paula , Rugo, Hope S , Clark, Amy S , Yee, Douglas , DeMichele, Angela , Petricoin, Emmanuel F , Chien, Jo , Stringer-Reasor, Erica , Shatsky, Rebecca , Liu, Minetta , Soliman, Hatem Hussein , Isaacs, Claudine , Nanda, Rita , Hylton, Nola M. , Pusztai, Lajos , Esserman, Laura J , Veer, Laura J. van’t , Campbell, Michael, Investigators, I-SPY2, Symmans, W. Fraser , Rugo, Hope S. , DeMichele, Angela , Shatsky, Rebecca , Han, Hyo S , Isaacs, Claudine , Pusztai, Lajos , Esserman, Laura J. , Mukhtar, Rita A. , Wallace, Anne M. , Yeung, Kay T. , Olopade, Olufunmilayo I. , Potter, David, Blaes, Anne , Boughey, Judy C. , Elias, Anthony , Mitri, Zahi Ibrahim , Lang, Julie E. , Thomas, Alexandra , Trivedi, Meghna S. , Hershman, Dawn L. , Meisel, Jane Lowe , Kalinsky, Kevin M. , Vaklavas, Christos , Sanft, Tara , Arora, Mili, Falkson, Carla I. , Murthy, Rashmi Krishna
JCO Precision Oncology | June 17, 2025 | Volume: No volume available | Issue: 9 | Pages: No page available
PURPOSE Neoadjuvant immunotherapy (IO) has become the standard of care for early-stage triple-negative breast cancer (TNBC), but not yet for other subtypes. We previously developed a clinical-grade mRNA-based immune classifier (ImPrint) predicting response to IO that is now being used in I-SPY2.2 as part of the response predictive subtypes. We report the performance of ImPrint in hormone receptor–positive and human epidermal growth factor receptor 2–negative (HR+HER2–) patients from five IO arms. METHODS A total of 204 HR+HER2– (MammaPrint high-risk) patients from five IO arms (anti–PD-1, anti–PD-L1/poly [ADP-ribose] polymerase inhibitor combination, anti–PD-1/toll-like receptor 9 dual-IO combination, and anti–PD-1 ± lymphocyte activation gene 3 dual-IO combination) and 191 patients from the chemotherapy-only control arm were included in this analysis. Patients were classified as ImPrint+ (likely sensitive) versus ImPrint– (likely resistant), using pretreatment mRNA. Performance of ImPrint for predicting pathologic complete response (pCR) to IO-containing arms was characterized and compared with tumor grade (III), MammaPrint (ultra) High2 risk (MP2), and estrogen receptor (ER)-low (ER ≤ 10%). RESULTS Overall, the pCR rate across the five IO arms was 33%. 26% of HR+HER2– patients were ImPrint+, and pCR rates with IO were 75% in ImPrint+ versus 17% in ImPrint–, with the highest pCR rate >90% in a dual-IO arm. In the control arm, pCR rates were 33% in ImPrint+ and 8% in ImPrint–. Tumor grade (III), MP2, and ER-low showed pCR rates in IO of 45%, 56%, and 63%, respectively, with lower pCR odds ratios (OR < 7.5) compared with ImPrint (OR = 14.5). CONCLUSION Using an accurate selection strategy, HR+HER2– patients could achieve pCR rates similar to what is seen with best neoadjuvant therapies in TNBC and HER2+ (ie, pCR rate >65%-70%). ImPrint, an Food and Drug Administration IDE-enabled assay, may represent a way to identify HR+HER2– patients for IO that best balances likely benefit versus risk of serious immune-related adverse events.