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Clin Cancer Res. 2017 Aug 15;23(16):4662-4670. doi: 10.1158/1078-0432.CCR-17-0160. Epub 2017 May 9.

The Longitudinal Transcriptional Response to Neoadjuvant Chemotherapy with and without Bevacizumab in Breast Cancer.

Author information

1
Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
2
Department of Oncology, Oslo University Hospital, Oslo, Norway.
3
Department of Pathology, Oslo University Hospital, Oslo, Norway.
4
Department of Research, Vestre Viken Hospital Trust, Drammen, Norway.
5
Department of Radiology and Nuclear Medicine, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
6
Department of Breast and Endocrine Surgery, Oslo University Hospital, Oslo, Norway.
7
Department of Oncology, St. Olavs University Hospital, Trondheim, Norway.
8
Department of Cancer Research and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
9
Insitute for Clinical Medicine, University of Oslo, Oslo, Norway.
10
Department of Computer Science, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.
11
Department of Oncology, Oslo University Hospital, Oslo, Norway. olav.engebraten@medisin.uio.no.

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.

PMID:
28487444
DOI:
10.1158/1078-0432.CCR-17-0160
[Indexed for MEDLINE]
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