6P - HbA1c as a prognostic biomarker in early breast cancer among patients without diabetes

Background

Pre-existing diabetes in patients with breast cancer (BC) is associated with inferior prognosis, potentially due to hyperglycemia, which is also associated with tumor growth. Chronic hyperglycemia translates into higher levels of glycosylated hemoglobin (HbA1c). We hypothesized that increased HbA1c is associated with inferior prognosis in patients with BC without diabetes.

Methods

We assembled a cohort of women diagnosed with stage I-III BC during 2010-2020 who consented to give a blood sample at the time of BC diagnosis (single institution) without diabetes diagnosed at the time of blood draw. HbA1c levels were treated as categorical (divided into quartiles) and continuous variables. We followed patients from date of surgery to the first of BC recurrence, contralateral BC, mortality, emigration, or end-of-follow-up (15^th Nov, 2021). We used Cox regression to estimate hazard ratios (HRs) and associated 95% confidence intervals (95%CI) of BC recurrence (incl. contralateral BC) and mortality, according to HbA1c levels, adjusting for patient, tumor, and treatment characteristics.

Results

Among 2,514 patients and 14,126 years of follow-up, 205 recurrences, 43 contralateral BCs, and 271 deaths occurred. Patients within the highest HbA1c quartile(Q4) had an increased risk of recurrence compared with low HbA1c(Q1) in both crude and adjusted analyses (HbA1c-Q4: HR_cru=1.72, 95%CI=1.19-2.47; HR_adj 1.82, 95%CI=1.17-2.81). An increased risk of recurrence was also seen per mmol/mol HbA1c increase, although less clear in the adjusted analysis (HR_cru=1.02, 95%CI=1.00-1.04; HR_adj 1.01, 95%CI=0.99-1.04). Patients with high HbA1c(Q4) had an increased risk of death (HbA1c-Q4: HR_cru=1.88, 95%CI=1.35-2.61) compared with patients in HbA1c-Q1, which attenuated in the adjusted analysis (HbA1c-Q4: HR_adj=1.10, 95%CI=0.75-1.62). An increased risk of death was seen per mmol/mol HbA1c increase in the crude analysis (HR_cru=1.03, 95%CI=1.02-1.04; HR_adj 1.00, 95%CI=0.98-1.02).

Conclusions

High HbA1c levels at the time of BC diagnosis were associated with increased risk of recurrence and death in patients with BC without diabetes. If validated, routine metabolic screening and potential correction of HbA1c in patients with BC could improve clinical outcome.

Legal entity responsible for the study

The authors.

Funding

Novo Nordisk Foundation, NEYE Foundation, the Danish Cancer Society, Fagerlund Stiftelsen, and the Department of Oncology Research Foundation.

Disclosure

All authors have declared no conflicts of interest.