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The longitudinal transcriptional response to neoadjuvant chemotherapy with and without bevacizumab in breast cancer
Authors
Elin Borgen
Anne-Lise Børresen-Dale
+24 more
Olav Engebråten
Anne Fangberget
Thomas Fleischer
Øystein Garred
Hedda Gythfeldt
Marit Muri Holmen
Vessela N. Kristensen
Marit Krohn
Anita Langerød
Ole Christian Lingjærde
Steinar Lundgren
Elen Kristine Møller
Bjørn Naume
Silje Nord
Tone Olsen
Einar Andreas Rødland
Ellen Schlichting
Laxmi Silwal-Pandit
Helle Skjerven
Mette Norberg Stokke
Hans Kristian Moen Vollan
Phuong Ngoc Thi Vu
Elisabeth Wille
Erik Wist
Publication date
1 January 2017
Publisher
'American Association for Cancer Research (AACR)'
Doi
Cite
Abstract
Purpose: Chemotherapy-induced alterations to gene expression are due to transcriptional reprogramming of tumor cells or subclonal adaptations to treatment. The effect on whole-transcriptome mRNA expression was investigated in a randomized phase II clinical trial to assess the effect of neoadjuvant chemotherapy with the addition of bevacizumab. Experimental Design: Tumor biopsies and whole-transcriptome mRNA profiles were obtained at three fixed time points with 66 patients in each arm. Altogether, 358 specimens from 132 patients were available, representing the transcriptional state before treatment start, at 12 weeks and after treatment (25 weeks). Pathologic complete response (pCR) in breast and axillary nodes was the primary endpoint. Results: pCR was observed in 15 patients (23%) receiving bevacizumab and chemotherapy and 8 patients (12%) receiving only chemotherapy. In the estrogen receptor–positive patients, 11 of 54 (20%) treated with bevacizumab and chemotherapy achieved pCR, while only 3 of 57 (5%) treated with chemotherapy reached pCR. In patients with estrogen receptor–positive tumors treated with combination therapy, an elevated immune activity was associated with good response. Proliferation was reduced after treatment in both treatment arms and most pronounced in the combination therapy arm, where the reduction in proliferation accelerated during treatment. Transcriptional alterations during therapy were subtype specific, and the effect of adding bevacizumab was most evident for luminal-B tumors. Conclusions: Clinical response and gene expression response differed between patients receiving combination therapy and chemotherapy alone. The results may guide identification of patients likely to benefit from antiangiogenic therapy. Clin Cancer Res; 23(16); 4662–70. ©2017 AACR
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NORA - Norwegian Open Research Archives
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oai:www.duo.uio.no:10852/59918
Last time updated on 08/02/2018
NORA - Norwegian Open Research Archives
See this paper in CORE
Go to the repository landing page
Download from data provider
oai:ntnuopen.ntnu.no:11250/248...
Last time updated on 14/10/2021