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

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 (+8 others)
2021 Cancers  

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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
more » ... utations 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.
doi:10.3390/cancers13194884 pmid:34638369 pmcid:PMC8508505 fatcat:v6djccbajfbvrikhskohmofvha
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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. "Immune Markers and Tumor-Related Processes Predict Neoadjuvant Therapy Response in the WSG-ADAPT HER2-Positive/Hormone Receptor-Positive Trial in Early Breast Cancer." Cancers 13.19 (2021) 4884