Immune Markers and Tumor-Related Processes Predict Neoadjuvant Therapy Response in the WSG-ADAPT HER2-Positive/Hormone Receptor-Positive Trial in Early Breast Cancer.

Abstract

Prognostic or predictive biomarkers in HER2-positive early breast cancer (EBC) may inform treatment optimization. The ADAPT HER2-positive/hormone receptor-positive phase II trial (NCT01779206) demonstrated pathological complete response (pCR) rates of ~40% following de-escalated treatment with 12 weeks neoadjuvant ado-trastuzumab emtansine (T-DM1) ± endocrine therapy. In this exploratory analysis, we evaluated potential early predictors of response to neoadjuvant therapy. The effects of PIK3CA mutations and immune (CD8 and PD-L1) and apoptotic markers (BCL2 and MCL1) on pCR rates were assessed, along with intrinsic BC subtypes. Immune response and pCR were lower in PIK3CA-mutated tumors compared with wildtype. Increased BCL2 at baseline in all patients and at Cycle 2 in the T-DM1 arms was associated with lower pCR. In the T-DM1 arms only, the HER2-enriched subtype was associated with increased pCR rate (54% vs. 28%). These findings support further prospective pCR-driven de-escalation studies in patients with HER2-positive EBC.

• Authors: Nadia Harbeck, Raquel von Schumann, Ronald Ernest Kates, Michael Braun, Sherko Kuemmel, Claudia Schumacher, Jochem Potenberg, Wolfram Malter, Doris Augustin, Bahriye Aktas, Helmut Forstbauer, Joke Tio, Eva-Maria Grischke, Claudia Biehl, Cornelia Liedtke, Sanne Lysbet De Haas, Regula Deurloo, Rachel Wuerstlein, Hans Heinrich Kreipe, Oleg Gluz
• Journal: Cancers (Cancers (Basel)) Vol. 13 Issue 19 (Sep 29 2021) ISSN: 2072-6694 [Print] Switzerland
• PMID: 34638369 (Publication Type: Journal Article)