Upregulation of IGF-1R expression during neoadjuvant therapy predicts poor outcome in breast cancer patients

Sandra Heskamp; Otto C Boerman; Janneke D M Molkenboer-Kuenen; Carla A Wauters; Luc J A Strobbe; Caroline M P W Mandigers; Peter Bult; Wim J G Oyen; Winette T A van der Graaf; Hanneke W M van Laarhoven

doi:10.1371/journal.pone.0117745

Upregulation of IGF-1R expression during neoadjuvant therapy predicts poor outcome in breast cancer patients

PLoS One. 2015 Feb 13;10(2):e0117745. doi: 10.1371/journal.pone.0117745. eCollection 2015.

Affiliations

¹ Department of Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
² Department of Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
³ Department of Pathology, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands.
⁴ Department of Surgery, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands.
⁵ Department of Internal Medicine, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands.
⁶ Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
⁷ Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
⁸ Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

Abstract

Introduction: The insulin-like growth factor 1 receptor (IGF-1R) may be involved in the development of resistance against conventional cancer treatment. The aim of this study was to assess whether IGF-1R expression of breast tumors changes during neoadjuvant therapy and to study whether these changes were associated with survival.

Methods: Paraffin embedded tumor tissue was collected from pretreatment biopsies and surgical resections of 62 breast cancer patients who were treated with neoadjuvant chemotherapy or endocrine therapy. IGF-1R expression was determined immunohistochemically and compared before and after treatment.

Results: High membranous IGF-1R expression at diagnosis correlated significantly with ER positivity, low tumor stage (stage I/II) and longer overall survival (p < 0.05). After neoadjuvant treatment, membranous IGF-1R expression remained the same in 41 (65%) tumors, was upregulated in 11 (18%) tumors and downregulated in 11 (18%) tumors. Changes in membranous IGF-1R expression were associated with overall survival (log-rank test: p = 0.013, multivariate cox-regression: p = 0.086). Mean overall survival time for upregulation, no change, and downregulation in IGF-1R expression was 3.0 ± 0.5 years, 7.3 ± 1.0 years and 15.0 ± 1.8 years, respectively. Changes in other parameters were not significantly associated with survival.

Conclusion: Neoadjuvant therapy can induce changes in IGF-1R expression. Upregulation of IGF-1R expression after neoadjuvant treatment is a poor prognostic factor in breast cancer patients, providing a rationale for incorporating anti-IGF-1R drugs in the management of these patients.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism
Breast Neoplasms / drug therapy
Breast Neoplasms / metabolism*
Breast Neoplasms / mortality*
Breast Neoplasms / pathology
Female
Follow-Up Studies
Gene Expression
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Middle Aged
Neoadjuvant Therapy
Neoplasm Staging
Prognosis
Receptor, IGF Type 1 / genetics
Receptor, IGF Type 1 / metabolism*
Up-Regulation

Substances

Biomarkers, Tumor
Receptor, IGF Type 1

Grants and funding

This study was financially supported by a personal research grant of the Dutch Research Council for Hanneke van Laarhoven (016.096.010). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.