Grote, Isabel ORCID: 0000-0002-6731-187X, Bartels, Stephan, Kandt, Leonie, Bollmann, Laura, Christgen, Henriette, Gronewold, Malte, Raap, Mieke, Lehmann, Ulrich, Gluz, Oleg, Nitz, Ulrike, Kuemmel, Sherko ORCID: 0000-0001-9355-494X, Zu Eulenburg, Christine, Braun, Michael, Aktas, Bahriye, Grischke, Eva-Maria, Schumacher, Claudia, Luedtke-Heckenkamp, Kerstin, Kates, Ronald, Wuerstlein, Rachel, Graeser, Monika, Harbeck, Nadia, Christgen, Matthias and Kreipe, Hans (2021). TP53 mutations are associated with primary endocrine resistance in luminal early breast cancer. Cancer Med., 10 (23). S. 8581 - 8595. HOBOKEN: WILEY. ISSN 2045-7634

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Abstract

Background Whereas the genomic landscape of endocrine-resistant breast cancer has been intensely characterized in previously treated cases with local or distant recurrence, comparably little is known about genomic alterations conveying primary non-responsiveness to endocrine treatment in luminal early breast cancer. Methods In this study, 622 estrogen receptor-expressing breast cancer cases treated with short-term preoperative endocrine therapy (pET) from the WSG-ADAPT trial (NCT01779206) were analyzed for genetic alterations associated with impaired endocrine proliferative response (EPR) to 3-week pET with tamoxifen or aromatase inhibitors. EPR was categorized as optimal (post-pET Ki67 <10%) versus slightly, moderately, and severely impaired (post-pET Ki67 10%-19%, 20%-34%, and >= 35%, respectively). Recently described gene mutations frequently found in previously treated advanced breast cancer were analyzed (ARID1A, BRAF, ERBB2, ESR1, GATA3, HRAS, KRAS, NRAS, PIK3CA, and TP53) by next-generation sequencing. Amplifications of CCND1, FGFR1, ERBB2, and PAK1 were determined by digital PCR or fluorescence in situ hybridization. Results ERBB2 amplification (p = 0.0015) and mutations of TP53 (p < 0.0001) were significantly associated with impaired EPR. Impaired EPR in TP53-mutated breast cancer cases was independent from the Oncotype DX Recurrence Score group and was seen both with tamoxifen- and aromatase inhibitor-based pET (p = 0.0005 each). Conclusion We conclude that impaired EPR to pET is suitable to identify cases with primary endocrine resistance in early luminal breast cancer and that TP53-mutated luminal cancers might not be sufficiently treated by endocrine therapy alone.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Grote, IsabelUNSPECIFIEDorcid.org/0000-0002-6731-187XUNSPECIFIED
Bartels, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kandt, LeonieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bollmann, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Christgen, HenrietteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gronewold, MalteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Raap, MiekeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lehmann, UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gluz, OlegUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nitz, UlrikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuemmel, SherkoUNSPECIFIEDorcid.org/0000-0001-9355-494XUNSPECIFIED
Zu Eulenburg, ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Braun, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aktas, BahriyeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grischke, Eva-MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schumacher, ClaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Luedtke-Heckenkamp, KerstinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kates, RonaldUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wuerstlein, RachelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Graeser, MonikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Harbeck, NadiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Christgen, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kreipe, HansUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-602916
DOI: 10.1002/cam4.4376
Journal or Publication Title: Cancer Med.
Volume: 10
Number: 23
Page Range: S. 8581 - 8595
Date: 2021
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 2045-7634
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PROGNOSTIC VALUE; THERAPY; KI67; EXPRESSION; TAMOXIFEN; SURVIVAL; LESSONS; BENEFIT; WOMENMultiple languages
OncologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60291

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