20P - Prognostic implications of IGF-1R expression in breast cancer overall and across body mass index groups

Background

The insulin-like growth factor 1 receptor (IGF1R) is involved in cell growth, including cancer cells. Studies have shown varying results regarding the prognostic potential in breast cancer (BC), which may differ according to patient-related factors, i.e. obesity (body mass index (BMI) >30 kg/m²). Obesity is associated with inferior BC prognosis. Here, we hypothesize that tumor IGF1R expression is associated with prognosis in BC patients overall and across BMI groups.

Methods

The study is based on the Malmö Diet and Cancer Study, a prospective cohort study that included participants between 1991 and 1996. A total of 718 women with incident invasive BC diagnosed 1991-2010 were included. IGF1R expression was annotated in the cancer cell cytoplasm (low/high) and membrane (negative/positive) by immunohistochemical staining of tissue microarrays. We followed patients from BC diagnosis date until recurrence, death, emigration, or last day of follow-up (8^th June, 2020). We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (95%CI) of recurrence and death according to IGF1R levels, adjusted for patient and tumor characteristics.

Results

Among 667 BC patients with evaluable IGF1R levels, 174 recurrences and 262 deaths occurred during 8,633 person-years of follow-up. No association between high cytoplasm IGF1R and recurrence risk was observed compared to low IGF1R (HR_cru 1.09 [95%CI 0.80-1.47]; HR_adj 0.97 [95%CI 0.69-1.37]). Similar results were seen for membraneous IGF1R. High cytoplasm IGF1R was associated with increased risk of death in crude analysis (HR_cru 1.75 [95%CI 1.37-2.24]; HR_adj 1.18 [95%CI 0.88-1.57]). Membrane IGF1R positivity was associated with an increased risk of death in crude and adjusted analyses (HR_cru 1.86 [95%CI 1.40-2.45]; HR_adj 1.48 [95%CI 1.07-2.04]). In patients with obesity (n=104), preliminary results suggest that high cytoplasm IGF1R is associated with lower recurrence risk compared to low IGF1R in adjusted analysis (HR_adj 0.36 [95%CI 0.13-0.95]).

Conclusions

In BC patients, high IGF1R tumor expression in cytoplasm and membrane was associated with increased risk of death, but not recurrence. In BC patients with obesity, high IGF1R may be associated with decreased risk of recurrence.

Legal entity responsible for the study

The authors.

Funding

Aarhus University, Mrs Berta KampradFoundation, Swedish Breast Cancer Association, Governmental Funding of Clinical Research within the National Health Service (ALF-Project).

Disclosure

All authors have declared no conflicts of interest.