Research ExplorerPublicationsTP53 mutations are associated with primary endocrine resista...

TP53 mutations are associated with primary endocrine resistance in luminal early breast cancer

Standard

TP53 mutations are associated with primary endocrine resistance in luminal early breast cancer. / Grote, Isabel; Bartels, Stephan; Kandt, Leonie; Bollmann, Laura; Christgen, Henriette; Gronewold, Malte; Raap, Mieke; Lehmann, Ulrich; Gluz, Oleg; Nitz, Ulrike; Kuemmel, Sherko; 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; Kreipe, Hans.

In: CANCER MED-US, Vol. 10, No. 23, 12.2021, p. 8581-8594.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Grote, I, Bartels, S, Kandt, L, Bollmann, L, Christgen, H, Gronewold, M, Raap, M, Lehmann, U, Gluz, O, Nitz, U, Kuemmel, S, Zu Eulenburg, C, Braun, M, Aktas, B, Grischke, E-M, Schumacher, C, Luedtke-Heckenkamp, K, Kates, R, Wuerstlein, R, Graeser, M, Harbeck, N, Christgen, M & Kreipe, H 2021, 'TP53 mutations are associated with primary endocrine resistance in luminal early breast cancer', CANCER MED-US, vol. 10, no. 23, pp. 8581-8594. https://doi.org/10.1002/cam4.4376

APA

Grote, I., Bartels, S., Kandt, L., Bollmann, L., Christgen, H., Gronewold, M., Raap, M., Lehmann, U., Gluz, O., Nitz, U., Kuemmel, S., Zu Eulenburg, C., Braun, M., Aktas, B., Grischke, E-M., Schumacher, C., Luedtke-Heckenkamp, K., Kates, R., Wuerstlein, R., ... Kreipe, H. (2021). TP53 mutations are associated with primary endocrine resistance in luminal early breast cancer. CANCER MED-US, 10(23), 8581-8594. https://doi.org/10.1002/cam4.4376

Vancouver

Grote I, Bartels S, Kandt L, Bollmann L, Christgen H, Gronewold M et al. TP53 mutations are associated with primary endocrine resistance in luminal early breast cancer. CANCER MED-US. 2021 Dec;10(23):8581-8594. https://doi.org/10.1002/cam4.4376

Bibtex

@article{588f07684e1e4d6cad26564be34a3dbf,
title = "TP53 mutations are associated with primary endocrine resistance in luminal early breast cancer",
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.",
author = "Isabel Grote and Stephan Bartels and Leonie Kandt and Laura Bollmann and Henriette Christgen and Malte Gronewold and Mieke Raap and Ulrich Lehmann and Oleg Gluz and Ulrike Nitz and Sherko Kuemmel and {Zu Eulenburg}, Christine and Michael Braun and Bahriye Aktas and Eva-Maria Grischke and Claudia Schumacher and Kerstin Luedtke-Heckenkamp and Ronald Kates and Rachel Wuerstlein and Monika Graeser and Nadia Harbeck and Matthias Christgen and Hans Kreipe",
note = "{\textcopyright} 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.",
year = "2021",
month = dec,
doi = "10.1002/cam4.4376",
language = "English",
volume = "10",
pages = "8581--8594",
journal = "CANCER MED-US",
issn = "2045-7634",
publisher = "John Wiley and Sons Ltd",
number = "23",

}

RIS

TY - JOUR

T1 - TP53 mutations are associated with primary endocrine resistance in luminal early breast cancer

AU - Grote, Isabel

AU - Bartels, Stephan

AU - Kandt, Leonie

AU - Bollmann, Laura

AU - Christgen, Henriette

AU - Gronewold, Malte

AU - Raap, Mieke

AU - Lehmann, Ulrich

AU - Gluz, Oleg

AU - Nitz, Ulrike

AU - Kuemmel, Sherko

AU - Zu Eulenburg, Christine

AU - Braun, Michael

AU - Aktas, Bahriye

AU - Grischke, Eva-Maria

AU - Schumacher, Claudia

AU - Luedtke-Heckenkamp, Kerstin

AU - Kates, Ronald

AU - Wuerstlein, Rachel

AU - Graeser, Monika

AU - Harbeck, Nadia

AU - Christgen, Matthias

AU - Kreipe, Hans

N1 - © 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

PY - 2021/12

Y1 - 2021/12

N2 - 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.

AB - 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.

U2 - 10.1002/cam4.4376

DO - 10.1002/cam4.4376

M3 - SCORING: Journal article

C2 - 34779146

VL - 10

SP - 8581

EP - 8594

JO - CANCER MED-US

JF - CANCER MED-US

SN - 2045-7634

IS - 23

ER -