TY - JOUR
T1 - Upregulation of IGF-1R Expression during Neoadjuvant Therapy Predicts Poor Outcome in Breast Cancer Patients
AU - Heskamp, Sandra
AU - Boerman, Otto C.
AU - Molkenboer-Kuenen, Janneke D. M.
AU - Wauters, Carla A.
AU - Strobbe, Luc J. A.
AU - Mandigers, Caroline M. P. W.
AU - Bult, Peter
AU - Oyen, Wim J. G.
AU - van der Graaf, Winette T. A.
AU - van Laarhoven, Hanneke W. M.
PY - 2015
Y1 - 2015
N2 - 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
AB - 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
U2 - https://doi.org/10.1371/journal.pone.0117745
DO - https://doi.org/10.1371/journal.pone.0117745
M3 - Article
C2 - 25680198
SN - 1932-6203
VL - 10
SP - e0117745
JO - PLOS ONE
JF - PLOS ONE
IS - 2
ER -