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Association between insulin-like growth factor-1 receptor (IGF1R) negativity and poor prognosis in a cohort of women with primary breast cancer
Lund University, Sweden.
Lund University, Sweden; Skåne University Hospital, Sweden.
Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
Lund University, Sweden; Skåne University Hospital, Sweden.
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2014 (English)In: BMC Cancer, ISSN 1471-2407, Vol. 14, no 794Article in journal (Refereed) Published
Abstract [en]

Background: Resistance towards endocrine therapy is a great concern in breast cancer treatment and may partly be explained by the activation of compensatory signaling pathways. The aim of the present study was to investigate if the insulin-like growth factor-1 receptor (IGF1R) signaling pathway was activated or deregulated in breast cancer patients and to explore if any of the markers were prognostic, with or without adjuvant tamoxifen. This signaling pathway has been suggested to cause estrogen independent cell growth and thus contribute to resistance to endocrine treatment in estrogen receptor (ER) positive breast cancer. Methods: The protein expression of IGF1R, phosphorylated Mammalian Target of Rapamycin (p-mTOR) and phosphorylated S6 ribosomal protein (p-S6rp) were investigated by immunohistochemistry using tissue microarrays in two patient cohorts. Cohort I (N = 264) consisted of mainly postmenopausal women with stage II breast cancer treated with tamoxifen for 2 years irrespective of ER status. Cohort II (N = 206) consisted of mainly medically untreated, premenopausal patients with node-negative breast cancer. Distant disease-free survival (DDFS) at 5 years was used as end-point for survival analyses. Results: We found that lower IGF1R expression was associated with worse prognosis for tamoxifen treated, postmenopausal women (HR = 0.70, 95% CI = 0.52 - 0.94, p = 0.016). The effect was seen mainly in ER-negative patients where the prognostic effect was retained after adjustment for other prognostic markers (adjusted HR = 0.49, 95% CI = 0.29 - 0.82, p = 0.007). Expression of IGF1R was associated with ER positivity (p less than 0.001) in the same patient cohort. Conclusions: Our results support previous studies indicating that IGF1R positivity reflects a well differentiated tumor with low metastatic capacity. An association between lack of IGF1R expression and worse prognosis was mainly seen in the ER-negative part of Cohort I. The lack of co-activation of downstream markers (p-mTOR and p-S6rp) in the IGF1R pathway suggested that the prognostic effect was not due to complete activation of this pathway. Thus, no evidence could be found for a compensatory function of IGF1R signaling in the investigated cohorts.

Place, publisher, year, edition, pages
BioMed Central , 2014. Vol. 14, no 794
Keyword [en]
Primary breast cancer; Insulin-like growth factor-1 receptor; Estrogen receptor; Tamoxifen; Prognosis
National Category
Clinical Medicine
URN: urn:nbn:se:liu:diva-112813DOI: 10.1186/1471-2407-14-794ISI: 000345113300001PubMedID: 25362932OAI: diva2:777120

Funding Agencies|Swedish Cancer Society; Swedish Research Council; Gunnar Nilsson Cancer Foundation; Mrs. Berta Kamprad Foundation; Anna and Edwin Bergers foundation; Skane University Hospital Research Foundation; Skane County Councils Research and Development Foundation; Governmental Funding of Clinical Research within the National Health Service

Available from: 2015-01-08 Created: 2014-12-17 Last updated: 2015-01-08

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Olsson, Hans
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Division of Inflammation MedicineFaculty of Health SciencesDepartment of Clinical Pathology and Clinical Genetics
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