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

Heskamp S, Boerman OC, Molkenboer-Kuenen JD, Wauters CA, Strobbe LJ, Mandigers CM, Bult P, Oyen WJ, van der Graaf WT, van Laarhoven HW - PLoS ONE (2015)

Bottom Line: IGF-1R expression was determined immunohistochemically and compared before and after treatment.Changes in membranous IGF-1R expression were associated with overall survival (log-rank test: p = 0.013, multivariate cox-regression: p = 0.086).Changes in other parameters were not significantly associated with survival.

View Article: PubMed Central - PubMed

Affiliation: Department of Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Medical Oncology, Radboud University Medical Center, Nijmegen, 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.

No MeSH data available.


Related in: MedlinePlus

Kaplan-Meier survival curves.Kaplan-Meier survival curve estimates of overall survival of chemotherapy (A) or endocrine therapy (B) treated patients with a tumor showing a downregulation, no change or an upregulation in IGF-1R expression after neoadjuvant treatment (p = 0.060 and p = 0.069, respectively).
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pone.0117745.g003: Kaplan-Meier survival curves.Kaplan-Meier survival curve estimates of overall survival of chemotherapy (A) or endocrine therapy (B) treated patients with a tumor showing a downregulation, no change or an upregulation in IGF-1R expression after neoadjuvant treatment (p = 0.060 and p = 0.069, respectively).

Mentions: Since membranous IGF-1R expression changed during neoadjuvant treatment, we analyzed whether these changes were associated with OS. Kaplan-Meier analysis showed a significant association (log-rank test, p = 0.013, Fig. 2B). Patients whose tumors showed an increase in membranous IGF-1R expression after neoadjuvant therapy had a significantly shorter mean OS compared to patients with no change in expression or a downregulation. Mean OS time for an upregulation, no change, and a downregulation in membranous IGF-1R expression was 3.0 ± 0.5 years, 7.3 ± 1.0 years and 15.0 ± 1.8 years, respectively. Subgroup analysis for patients with metastatic versus non-metastatic disease is presented in Fig. 2B and 2C. In addition, the chemotherapy and endocrine therapy treated tumors were analyzed separately to determine whether the type of treatment may affect the association between change in IGF-1R and OS (Fig. 3). Although the numbers of patients in these subgroups were small, in both treatment groups the patients with a decrease in IGF-1R expression seem to have the longest overall survival (log-rank test chemotherapy p = 0.060, endocrine therapy p = 0.069).


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

Heskamp S, Boerman OC, Molkenboer-Kuenen JD, Wauters CA, Strobbe LJ, Mandigers CM, Bult P, Oyen WJ, van der Graaf WT, van Laarhoven HW - PLoS ONE (2015)

Kaplan-Meier survival curves.Kaplan-Meier survival curve estimates of overall survival of chemotherapy (A) or endocrine therapy (B) treated patients with a tumor showing a downregulation, no change or an upregulation in IGF-1R expression after neoadjuvant treatment (p = 0.060 and p = 0.069, respectively).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4334229&req=5

pone.0117745.g003: Kaplan-Meier survival curves.Kaplan-Meier survival curve estimates of overall survival of chemotherapy (A) or endocrine therapy (B) treated patients with a tumor showing a downregulation, no change or an upregulation in IGF-1R expression after neoadjuvant treatment (p = 0.060 and p = 0.069, respectively).
Mentions: Since membranous IGF-1R expression changed during neoadjuvant treatment, we analyzed whether these changes were associated with OS. Kaplan-Meier analysis showed a significant association (log-rank test, p = 0.013, Fig. 2B). Patients whose tumors showed an increase in membranous IGF-1R expression after neoadjuvant therapy had a significantly shorter mean OS compared to patients with no change in expression or a downregulation. Mean OS time for an upregulation, no change, and a downregulation in membranous IGF-1R expression was 3.0 ± 0.5 years, 7.3 ± 1.0 years and 15.0 ± 1.8 years, respectively. Subgroup analysis for patients with metastatic versus non-metastatic disease is presented in Fig. 2B and 2C. In addition, the chemotherapy and endocrine therapy treated tumors were analyzed separately to determine whether the type of treatment may affect the association between change in IGF-1R and OS (Fig. 3). Although the numbers of patients in these subgroups were small, in both treatment groups the patients with a decrease in IGF-1R expression seem to have the longest overall survival (log-rank test chemotherapy p = 0.060, endocrine therapy p = 0.069).

Bottom Line: IGF-1R expression was determined immunohistochemically and compared before and after treatment.Changes in membranous IGF-1R expression were associated with overall survival (log-rank test: p = 0.013, multivariate cox-regression: p = 0.086).Changes in other parameters were not significantly associated with survival.

View Article: PubMed Central - PubMed

Affiliation: Department of Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Medical Oncology, Radboud University Medical Center, Nijmegen, 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.

No MeSH data available.


Related in: MedlinePlus