Universität zu Köln

Harbeck, Nadia ORCID: 0000-0002-9744-7372, von Schumann, Raquel, Kates, Ronald Ernest, Braun, Michael, Kuemmel, Sherko ORCID: 0000-0001-9355-494X, Schumacher, Claudia, Potenberg, Jochem, Malter, Wolfram, Augustin, Doris, Aktas, Bahriye ORCID: 0000-0002-5474-051X, Forstbauer, Helmut, Tio, Joke, Grischke, Eva-Maria, Biehl, Claudia, Liedtke, Cornelia, De Haas, Sanne Lysbet, Deurloo, Regula, Wuerstlein, Rachel, Kreipe, Hans Heinrich and Gluz, Oleg (2021). 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). BASEL: MDPI. ISSN 2072-6694

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Abstract

Simple Summary: Patients with HER2-positive early breast cancer are treated with antibodies to the HER2 protein along with chemotherapy, regardless of whether their cancer also has hormone receptors, or of its molecular features. Because patients with HER2-positive/hormone receptor-positive disease tend to live longer than those with HER2-positive/hormone receptor-negative disease, there may be some patients who are being overtreated under current guidelines. The aim of our exploratory translational analysis of the ADAPT HER2-positive/hormone receptor-positive trial was to investigate the potential of several prognostic (outcome regardless of therapy) and predictive (effect of therapy) biomarkers as early predictors of response to treatment before surgery. Comparison of these biomarkers before and after one treatment cycle, and their effects on whether patients' cancers were completely removed at surgery, suggest that certain patients (those with treatment-induced CD8 protein-expressing cells infiltrating the cancer; without PIK3CA mutation; those with HER2-enriched tumors) may be candidates for less intensive treatment following pre-surgical therapy. 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 similar to 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Harbeck, Nadia UNSPECIFIED orcid.org/0000-0002-9744-7372 UNSPECIFIED von Schumann, Raquel UNSPECIFIED UNSPECIFIED UNSPECIFIED Kates, Ronald Ernest UNSPECIFIED UNSPECIFIED UNSPECIFIED Braun, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuemmel, Sherko UNSPECIFIED orcid.org/0000-0001-9355-494X UNSPECIFIED Schumacher, Claudia UNSPECIFIED UNSPECIFIED UNSPECIFIED Potenberg, Jochem UNSPECIFIED UNSPECIFIED UNSPECIFIED Malter, Wolfram UNSPECIFIED UNSPECIFIED UNSPECIFIED Augustin, Doris UNSPECIFIED UNSPECIFIED UNSPECIFIED Aktas, Bahriye UNSPECIFIED orcid.org/0000-0002-5474-051X UNSPECIFIED Forstbauer, Helmut UNSPECIFIED UNSPECIFIED UNSPECIFIED Tio, Joke UNSPECIFIED UNSPECIFIED UNSPECIFIED Grischke, Eva-Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Biehl, Claudia UNSPECIFIED UNSPECIFIED UNSPECIFIED Liedtke, Cornelia UNSPECIFIED UNSPECIFIED UNSPECIFIED De Haas, Sanne Lysbet UNSPECIFIED UNSPECIFIED UNSPECIFIED Deurloo, Regula UNSPECIFIED UNSPECIFIED UNSPECIFIED Wuerstlein, Rachel UNSPECIFIED UNSPECIFIED UNSPECIFIED Kreipe, Hans Heinrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Gluz, Oleg UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-604160
DOI:	10.3390/cancers13194884
Journal or Publication Title:	Cancers
Volume:	13
Number:	19
Date:	2021
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2072-6694
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GROWTH-FACTOR RECEPTOR; PATHOLOGICAL COMPLETE RESPONSE; TRASTUZUMAB EMTANSINE; PHASE-III; INFILTRATING LYMPHOCYTES; ADJUVANT TRASTUZUMAB; SECONDARY ANALYSIS; PIK3CA MUTATIONS; CHEMOTHERAPY; LAPATINIB Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/60416