Journal
CLINICAL CANCER RESEARCH
Volume 22, Issue 10, Pages 2405-2416Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-15-1488
Keywords
-
Categories
Funding
- Skane County Council's Research and Developmental Foundation
- Swedish Breast Cancer Association (BRO)
- Berta Kamprad Foundation
- Inger Persson Research Foundation
- Breakthrough Breast Cancer
- Royal Marsden NIHR Biomedical Research Centre
- CRUK Core grant [C1491/A15955]
- National Institute for Health Research [NF-SI-0512-10122] Funding Source: researchfish
Ask authors/readers for more resources
Purpose: The primary aim was to derive evidence for or against the clinical importance of several biologic processes in patients treated with neoadjuvant chemotherapy (NAC) by assessing expression of selected genes with prior implications in prognosis or treatment resistance. The secondary aim was to determine the prognostic impact in residual disease of the genes' expression. Experimental Design: Expression levels of 24 genes were quantified by NanoString nCounter on formalin-fixed paraffin-embedded residual tumors from 126 patients treated with NAC and 56 paired presurgical biopsies. The paired t test was used for testing changes in gene expression, and Cox regression and penalized elastic-net Cox Regression for estimating HRs. Results: After NAC, 12 genes were significantly up-and 8 downregulated. Fourteen genes were significantly associated with time to recurrence in univariable analysis in residual disease. In a multivariable model, ACACB, CD3D, MKI67, and TOP2A added prognostic value independent of clinical ER+, PgR(-) and HER2(-) tatus. In ER+/HER2(-) patients, ACACB, PAWR, and ERBB2 predicted outcome, whereas CD3D and PAWR were prognostic in ER+/HER2(-) patients. By use of elastic-net analysis, a 6-gene signature (ACACB, CD3D, DECORIN, ESR1, MKI67, PLAU) was identified adding prognostic value independent of ER, PgR, and HER2. Conclusions: Most of the tested genes were significantly enriched or depleted in response to NAC. Expression levels of genes representing proliferation, stromal activation, metabolism, apoptosis, stemcellness, immunologic response, and Ras-ERK activation predicted outcome in residual disease. Themultivariable gene models identified could, if validated, be used to identify patients needing additional post-neoadjuvant treatment to improve prognosis. (C) 2016 AACR.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available