# HbA1c levels and breast cancer prognosis in women without diabetes

## TL;DR

Higher HbA1c levels in non-diabetic breast cancer patients are linked to a greater risk of cancer recurrence, but not overall mortality.

## Contribution

This study identifies HbA1c as a potential metabolic biomarker for predicting breast cancer recurrence in non-diabetic patients.

## Key findings

- Higher HbA1c quartiles were associated with increased risk of new breast cancer events.
- No significant association was found between HbA1c levels and all-cause mortality.
- A log2(HbA1c) increase correlated with higher risk of cancer recurrence.

## Abstract

Diabetes is associated with impaired breast cancer prognosis; however, the effectiveness of glycosylated hemoglobin (HbA1c) as a prognostic biomarker in breast cancer remains uncertain, especially for patients without diabetes. We aimed to determine whether elevated HbA1c is associated with a worse prognosis in breast cancer patients without known diabetes.

The study population comprised women with primary invasive stage I-III breast cancer between 2010 and 2020 surgically treated at Aarhus University Hospital, Denmark, without a diabetes diagnosis at baseline. We assessed HbA1c at breast cancer diagnosis as a categorical (quartiles; HbA1c-Q1 = 21–33 mmol/mol, HbA1c-Q2 = 34–36 mmol/mol, HbA1c-Q3 = 37–38 mmol/mol, HbA1c-Q4 = ≥ 39 mmol/mol) and log2-transformed continuous variable. Follow-up began at the date of primary breast cancer surgery and continued until the first occurrence of either a new breast cancer event (loco-regional or distant recurrence, or contralateral breast cancer), new primary cancer other than breast cancer, death, emigration, or end-of-follow-up (November 15th, 2021). Cox regression models estimated crude and adjusted hazard ratios and associated 95% confidence intervals (95% CIs) of a new breast cancer event and all-cause mortality, adjusting for patient characteristics based on a directed acyclic graph. The lowest HbA1c quartile (HbA1c-Q1) was used as reference.

In total, 2514 women (median age 62 years) were included. During median 5.6 years follow-up for new breast cancer events, 230 (9.1%) events occurred. An escalating risk of new breast cancer events was observed with increasing HbA1c quartiles (adjusted hazard ratios, HbA1c-Q2: 1.09 [95% CI = 0.75–1.60]; HbA1c-Q3: 1.35 [95% CI = 0.88–2.07]; HbA1c-Q4: 1.69 [95% CI = 1.13–2.54]) compared to HbA1c-Q1. During median 6.0 years follow-up for all-cause mortality, 267 deaths (10.6%) occurred. No apparent association was evident between increasing HbA1c quartiles and all-cause mortality (adjusted hazard ratios, HbA1c-Q2: 0.75 [95% CI = 0.52–1.07]; HbA1c-Q3: 0.82 [95% CI = 0.55–1.21]; HbA1c-Q4: 1.06 [95% CI = 0.74–1.53]). Similarly, a log2(HbA1c) increase was associated with an increased risk of new breast cancer events, but not all-cause mortality.

For women with primary breast cancer and no known diagnosis of diabetes, higher levels of HbA1c were associated with an increased risk of new breast cancer events, but not all-cause mortality. HbA1c may serve as a prognostic metabolic biomarker for breast cancer patients without diabetes.

The online version contains supplementary material available at 10.1186/s12885-025-14121-z.