Dataset Information

Association between insulin-like growth factor-1 receptor (IGF1R) negativity and poor prognosis in a cohort of women with primary breast cancer.

ABSTRACT:

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 < 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.

SUBMITTER: Aaltonen KE

PROVIDER: S-EPMC4232733 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Publications

Association between insulin-like growth factor-1 receptor (IGF1R) negativity and poor prognosis in a cohort of women with primary breast cancer.

Aaltonen Kristina E KE Rosendahl Ann H AH Olsson Hans H Malmström Per P Hartman Linda L Fernö Mårten M

BMC cancer 20141103

<h4>Background</h4>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 e ...[more]

PMID: 25362932

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Project description:BACKGROUND:Racial disparities in breast cancer survival between Black and White women persist across all stages of breast cancer. The metabolic syndrome (MetS) of insulin resistance disproportionately affects more Black than White women. It has not been discerned if insulin resistance mediates the link between race and poor prognosis in breast cancer. We aimed to determine whether insulin resistance mediates in part the association between race and breast cancer prognosis, and if insulin receptor (IR) and insulin-like growth factor receptor (IGF-1R) expression differs between tumors from Black and White women. METHODS:We conducted a cross-sectional, multi-center study across ten hospitals. Self-identified Black women and White women with newly diagnosed invasive breast cancer were recruited. The primary outcome was to determine if insulin resistance, which was calculated using the homeostatic model assessment of insulin resistance (HOMA-IR), mediated the effect of race on prognosis using the multivariate linear mediation model. Demographic data, anthropometric measurements, and fasting blood were collected. Poor prognosis was defined as a Nottingham Prognostic Index (NPI) >?4.4. Breast cancer pathology specimens were evaluated for IR and IGF-1R expression by immunohistochemistry (IHC). RESULTS:Five hundred fifteen women were recruited (83% White, 17% Black). The MetS was more prevalent in Black women than in White women (40% vs 20%, p?<?0.0001). HOMA-IR was higher in Black women than in White women (1.9?±?1.2 vs 1.3?±?1.4, p?=?0.0005). Poor breast cancer prognosis was more prevalent in Black women than in White women (28% vs 15%. p?=?0.004). HOMA-IR was positively associated with NPI score (r?=?0.1, p?=?0.02). The mediation model, adjusted for age, revealed that HOMA-IR significantly mediated the association between Black race and poor prognosis (??=?0.04, 95% CI 0.005-0.009, p?=?0.002). IR expression was higher in tumors from Black women than in those from White women (79% vs 52%, p?=?0.004), and greater IR/IGF-1R ratio was also associated with higher NPI score (IR/IGF-1R?>? 1: 4.2?±?0.8 vs IR/IGF-1R?=?1: 3.9?±?0.8 vs IR/IGF-1R?<?1: 3.5?±?1.0, p?<?0.0001). CONCLUSIONS:In this multi-center, cross-sectional study of US women with newly diagnosed invasive breast cancer, insulin resistance is one factor mediating part of the association between race and poor prognosis in breast cancer.

Dataset Information

Association between insulin-like growth factor-1 receptor (IGF1R) negativity and poor prognosis in a cohort of women with primary breast cancer.

Background

Methods

Results

Conclusions

Publications

Association between insulin-like growth factor-1 receptor (IGF1R) negativity and poor prognosis in a cohort of women with primary breast cancer.

Similar Datasets

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