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Chronic hyperglycemia associated with reduced OS in early-stage breast cancer survivors

Erickson K. J Clin Oncol. 2010;doi:10.1200/JCO.2010.29.3183.

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Among breast cancer survivors, chronic elevated HbA1c levels are linked with a statistically significantly higher risk for all-cause mortality, according to data from a recent study. Researchers also found that 90% of women with elevated HbA1c levels did not report having diabetes or prediabetes.

“These data suggest that clinicians should consider measuring HbA1c in patients with breast cancer with symptoms of hyperglycemia or those at high risk for diabetes,” the researchers wrote.

Using blood samples from the Women’s Healthy Eating and Living Study, researchers measured HbA1c levels of 3,003 women who survived early-stage breast cancer. Women were observed for a median of 7.3 years for additional breast cancer events and for 10.3 years for all-cause mortality. The researchers used Cox regression analysis to determine whether baseline HbA1c levels predicted DFS and OS.

Chronic hyperglycemia was defined as HbA1c levels of at least 6.5%. Women with chronic hyperglycemia (5.8%) were an average of 3.5 years older, less likely to have a college education, be of nonwhite ethnicity, be obese and have advanced breast cancer at diagnosis, according to the researchers.

HbA1c was statistically significantly associated with OS (P<.001); 35% of women with HbA1c levels of more than 8% died within the follow-up period. In addition, women with HbA1c levels of 6.5% to 6.9% and at least 7% were 60% (HR=1.6; 95% CI, 1.00-2.57) and three times (HR=3.01; 95% CI, 2.05-4.43) more likely to die during follow-up, respectively, compared with women with HbA1C levels of less than 6.5%.

The HR for continuous HbA1c and OS was 1.20 (95% CI, 1.07-1.34), after adjusting for age, education, ethnicity and physical activity and health. According to the adjusted model, the risk for death among women with HbA1c of 6.5% to 6.9% was not statistically significant. However, HbA1C levels of at least 7% was associated with a 2.4-fold increased risk for death (HR=2.35; 95% CI, 1.56-3.54).

Data also revealed that for DFS there was a nonsignificant 30% increase in risk associated with HbA1c levels of at least 7% (HR=1.26; 95% CI, 0.78-2.02). Previously diagnosed vs. undiagnosed diabetes accounted for the increased risk, the researchers found during follow-up.

Using self-reported diabetes status to stratify the distribution of breast cancer events by HbA1C category, the researchers aimed to determine how undiagnosed disease affected the association between HbA1C and breast cancer events. Less than half of the 3% of patients with HbA1C levels of at least 7% (37 or 91) reported having diabetes on the baseline questionnaire and 10% of the 3% with HbA1C levels of 6.5% to 6.9% (nine of 94) reported diabetes.

Of those who reported having diabetes, 76.8% reported also using blood sugar-lowering medication and had a twofold higher rate of breast cancer events compared with those who did not report diabetes (32.6% vs. 15.6%). Thirteen women reported diabetes but no blood sugar-lowering medication use; two of these women had breast cancer events and HbA1c levels of at least 7%.

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