Holm Jonas Busk, Bruun Jens Meldgaard, Christiansen Peer, Thomsen Reimar Wernich, Frystyk Jan, Cronin-Fenton Deirdre, Borgquist Signe
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
BMC Cancer. 2025 Apr 28;25(1):790. doi: 10.1186/s12885-025-14121-z.
Diabetes is associated with impaired breast cancer prognosis; however, the effectiveness of glycosylated hemoglobin (HbA) as a prognostic biomarker in breast cancer remains uncertain, especially for patients without diabetes. We aimed to determine whether elevated HbA 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 HbA at breast cancer diagnosis as a categorical (quartiles; HbA-Q1 = 21-33 mmol/mol, HbA-Q2 = 34-36 mmol/mol, HbA-Q3 = 37-38 mmol/mol, HbA-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 HbA quartile (HbA-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 HbA quartiles (adjusted hazard ratios, HbA-Q2: 1.09 [95% CI = 0.75-1.60]; HbA-Q3: 1.35 [95% CI = 0.88-2.07]; HbA-Q4: 1.69 [95% CI = 1.13-2.54]) compared to HbA-Q1. During median 6.0 years follow-up for all-cause mortality, 267 deaths (10.6%) occurred. No apparent association was evident between increasing HbA quartiles and all-cause mortality (adjusted hazard ratios, HbA-Q2: 0.75 [95% CI = 0.52-1.07]; HbA-Q3: 0.82 [95% CI = 0.55-1.21]; HbA-Q4: 1.06 [95% CI = 0.74-1.53]). Similarly, a log2(HbA) 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 HbA were associated with an increased risk of new breast cancer events, but not all-cause mortality. HbA may serve as a prognostic metabolic biomarker for breast cancer patients without diabetes.
糖尿病与乳腺癌预后不良相关；然而，糖化血红蛋白（HbA）作为乳腺癌预后生物标志物的有效性仍不确定，尤其是对于无糖尿病患者。我们旨在确定HbA升高是否与无已知糖尿病的乳腺癌患者的较差预后相关。
研究人群包括2010年至2020年间在丹麦奥胡斯大学医院接受手术治疗的原发性I-III期浸润性乳腺癌女性，基线时无糖尿病诊断。我们将乳腺癌诊断时的HbA评估为分类变量（四分位数；HbA-Q1 = 21-33 mmol/mol，HbA-Q2 = 34-36 mmol/mol，HbA-Q3 = 37-38 mmol/mol，HbA-Q4 = ≥ 39 mmol/mol）和经log2转换的连续变量。随访从原发性乳腺癌手术日期开始，持续至首次出现以下任何一种情况：新的乳腺癌事件（局部区域或远处复发，或对侧乳腺癌）、非乳腺癌的新原发性癌症、死亡、移民或随访结束（2021年11月15日）。Cox回归模型估计新乳腺癌事件和全因死亡率的粗风险比和调整后风险比及相关的95%置信区间（95%CI），并根据有向无环图对患者特征进行调整。最低的HbA四分位数（HbA-Q1）用作参考。
总共纳入了2514名女性（中位年龄62岁）。在对新乳腺癌事件进行中位5.6年的随访期间，发生了230起事件（9.1%）。随着HbA四分位数的增加，新乳腺癌事件的风险逐渐升高（与HbA-Q1相比，调整后风险比，HbA-Q2：1.09 [95%CI = 0.75-1.60]；HbA-Q3：1.35 [95%CI = 0.88-2.07]；HbA-Q4：1.69 [95%CI = 1.13-2.54]）。在对全因死亡率进行中位6.0年的随访期间，有267人死亡（10.6%）。HbA四分位数增加与全因死亡率之间未发现明显关联（调整后风险比，HbA-Q2：0.75 [95%CI = 0.52-1.07]；HbA-Q3：0.82 [95%CI = 0.55-1.21]；HbA-Q4：1.06 [95%CI = 0.74-1.53]）。同样，log2（HbA）升高与新乳腺癌事件风险增加相关，但与全因死亡率无关。
对于原发性乳腺癌且无已知糖尿病诊断的女性，较高水平的HbA与新乳腺癌事件风险增加相关，但与全因死亡率无关。HbA可能作为无糖尿病乳腺癌患者的预后代谢生物标志物。
