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

Autor: Harbeck N; Breast Center, Department of Obstetrics and Gynecology and CCCLMU, University of Munich (LMU), Marchioninistrasse 15, 81377 Munich, Germany.; The West German Study Group, 41061 Mönchengladbach, Germany., von Schumann R; Evangelical Hospital Bethesda, 41061 Mönchengladbach, Germany., Kates RE; The West German Study Group, 41061 Mönchengladbach, Germany., Braun M; Red Cross Hospital, 80634 Munich, Germany., Kuemmel S; Evangelical Hospital Bethesda, 41061 Mönchengladbach, Germany.; Breast Unit, Kliniken Essen-Mitte, 45136 Essen, Germany.; Klinik für Gynäkologie mit Brustzentrum Charité-Universitätsmedizin, 10117 Berlin, Germany., Schumacher C; St Elisabeth-Krankenhaus, 50935 Cologne, Germany., Potenberg J; Evangelischen Waldkrankenhaus Spandau, 13589 Berlin, Germany., Malter W; Breast Center, Department of Obstetrics and Gynecology, University Hospital Cologne, 50937 Cologne, Germany., Augustin D; Breast Center, Clinic Deggendorf, 94469 Deggendorf, Germany., Aktas B; University of Essen, 45147 Essen, Germany., Forstbauer H; Onkologie Rheinsieg, 53840 Troisdorf, Germany., Tio J; University Hospital Münster, 48149 Münster, Germany., Grischke EM; University Hospital of Tübingen, 72076 Tübingen, Germany., Biehl C; Westphalian Breast Center, City Hospital Dortmund, 44137 Dortmund, Germany., Liedtke C; University of Lübeck, 23562 Lübeck, Germany., De Haas SL; F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland., Deurloo R; F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland., Wuerstlein R; Breast Center, Department of Obstetrics and Gynecology and CCCLMU, University of Munich (LMU), Marchioninistrasse 15, 81377 Munich, Germany., Kreipe HH; Hannover Medical School, 30625 Hannover, Germany., Gluz O; The West German Study Group, 41061 Mönchengladbach, Germany.; Evangelical Hospital Bethesda, 41061 Mönchengladbach, Germany.; Breast Center, Department of Obstetrics and Gynecology, University Hospital Cologne, 50937 Cologne, Germany.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2021 Sep 29; Vol. 13 (19). Date of Electronic Publication: 2021 Sep 29.
DOI: 10.3390/cancers13194884
Abstrakt: 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.
Databáze: MEDLINE
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