Gluz, Oleg, Kolberg-Liedtke, Cornelia, Prat, Aleix ORCID: 0000-0003-2377-540X, Christgen, Matthias, Gebauer, Daniel, Kates, Ronald, Pare, Laia ORCID: 0000-0002-4904-558X, Grischke, Eva-Maria, Forstbauer, Helmut, Braun, Michael, Warm, Mathias, Hackmann, John, Uleer, Christoph, Aktas, Bahriye, Schumacher, Claudia, Kuemmel, Sherko, Wuerstlein, Rachel, Pelz, Enrico, Nitz, Ulrike, Kreipe, Hans Heinrich and Harbeck, Nadia (2020). Efficacy of deescalated chemotherapy according to PAM50 subtypes, immune and proliferation genes in triple-negative early breast cancer: Primary translational analysis of the WSG-ADAPT-TN trial. Int. J. Cancer, 146 (1). S. 262 - 272. HOBOKEN: WILEY. ISSN 1097-0215

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Abstract

In the neoadjuvant WSG-ADAPT-TN trial, 12-week nab-paclitaxel + carboplatin (nab-pac/carbo) was highly effective and superior to nab-paclitaxel + gemcitabine (nab-pac/gem) in triple-negative breast cancer regarding pathological complete response (pCR). Predictive markers for deescalated taxane/carbo use in TNBC need to be identified. Patients received 4 x nab-pac 125 mg/m(2) (plus carbo AUC2 or gem 1,000 mg/m(2) d1,8 q21). Expression of 119 genes and PAM50 scores by nCounter were available in 306/336 pretherapeutic samples. Interim survival analysis was planned after 36 months median follow-up. Basal-like (83.3%) compared to other subtypes was positively associated with pCR (38% vs. 20%, p = 0.015), as was lower HER2 score (p < 0.001). Proliferation biomarkers were positively associated with pCR, that is, PAM50 proliferation, ROR scores (all p < 0.004), higher Ki-67 (IHC; p < 0.001). For nab-pac/carbo, expression of immunological (CD8, PD1 and PFDL1) genes and proliferation markers (proliferation and ROR scores, MKI67, CDC20, NUF2, KIF2C, CENPF, EMP3 and TYMS) were positively associated with pCR (p < 0.05 for all). For nab-pac/gem, angiogenesis genes were negatively associated with pCR (ANGPTL4: p = 0.05; FGFR4: p = 0.02; VEGFA: p = 0.03). pCR after 12 weeks was strongly associated with favorable outcome (3y event-free survival: 92% vs. 71%, p < 0.001). In early TNBC, basal-like subtype, higher Ki-67 (IHC) and lower HER2 score were, associated with chemosensitivity. Chemoresistance pathways differed between the two taxane based combinations. Combination of proliferation/immune markers and PAM50 subtype could allow patient selection for further deescalated chemotherapy and/or immune treatment approaches.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Gluz, OlegUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kolberg-Liedtke, CorneliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Prat, AleixUNSPECIFIEDorcid.org/0000-0003-2377-540XUNSPECIFIED
Christgen, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gebauer, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kates, RonaldUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pare, LaiaUNSPECIFIEDorcid.org/0000-0002-4904-558XUNSPECIFIED
Grischke, Eva-MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Forstbauer, HelmutUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Braun, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Warm, MathiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hackmann, JohnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Uleer, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aktas, BahriyeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schumacher, ClaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuemmel, SherkoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wuerstlein, RachelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pelz, EnricoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nitz, UlrikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kreipe, Hans HeinrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Harbeck, NadiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-352734
DOI: 10.1002/ijc.32488
Journal or Publication Title: Int. J. Cancer
Volume: 146
Number: 1
Page Range: S. 262 - 272
Date: 2020
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1097-0215
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PATHOLOGICAL COMPLETE RESPONSE; TUMOR-INFILTRATING LYMPHOCYTES; NEOADJUVANT CHEMOTHERAPY; CARBOPLATIN; PACLITAXEL; SURVIVAL; RISK; THERAPY; CYCLOPHOSPHAMIDE; IDENTIFICATIONMultiple languages
OncologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/35273

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