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

• Published in: PloS one Vol. 10; no. 2; p. e0117745
• Main Authors: Heskamp, Sandra, Boerman, Otto C, Molkenboer-Kuenen, Janneke D M, Wauters, Carla A, Strobbe, Luc J A, Mandigers, Caroline M P W, Bult, Peter, Oyen, Wim J G, van der Graaf, Winette T A, van Laarhoven, Hanneke W M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13.02.2015; Public Library of Science (PLoS)
• Subjects: Adjuvant chemotherapy; Aged; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Biopsy; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Cancer; Cancer patients; Cancer therapies; Chemotherapy; Colorectal cancer; Comparative analysis; Endocrine therapy; Female; Follow-Up Studies; Gene Expression; Hospitals; Humans; Immunohistochemistry; Insulin; Insulin-like growth factors; Kaplan-Meier Estimate; Kinases; Laboratories; Medical diagnosis; Medical prognosis; Medical research; Metastasis; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Nuclear medicine; Oncology; Paraffin; Pathology; Patient outcomes; Patients; Prognosis; Receptor, IGF Type 1 - genetics; Receptor, IGF Type 1 - metabolism; Surgery; Survival; Tumors; Up-Regulation; Netherlands
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0117745

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. 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. 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. 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.