Clinically defined type 2 diabetes mellitus and prognosis in early-stage breast cancer.
OBJECTIVE
Self-reported diabetes has been associated with poor breast cancer outcomes. Research is needed to investigate the relationship between biologically determined glycemic control and breast cancer prognosis.


METHODS
Archived baseline blood samples from the Women's Healthy Eating and Living Study were used to measure hemoglobin A1C (HbA1C) among 3,003 survivors of early-stage breast cancer (age of diagnosis, 28 to 70 years) observed for a median of 7.3 years for additional breast cancer events and 10.3 years for all-cause mortality. HbA1C levels provide an accurate, precise measure of chronic glycemic levels. Cox regression analysis was performed to assess whether baseline HbA1C levels predicted disease-free and overall survival.


RESULTS
Only 5.8% of women had chronic hyperglycemia (defined as HbA1C levels ≥ 6.5%). Those with HbA1C ≥ 6.5% were older and more likely to be less educated, have nonwhite ethnicity, be obese, and have more advanced breast cancer at diagnosis. HbA1C was significantly associated with overall survival (P(trend) < .001). After adjusting for confounders, risk of all-cause mortality was twice as high in women with HbA1C ≥ 7.0% compared with women with HbA1C less than 6.5% (hazard ratio [HR], 2.35; 95% CI, 1.56 to 3.54). For disease-free survival, there was a nonsignificant 30% increase in risk for HbA1C levels ≥ 7.0% (HR, 1.26; 95% CI, 0.78 to 2.02). During study follow-up, previously diagnosed rather than undiagnosed diabetes seemed to account for the increased risk.


CONCLUSIONS
Chronic hyperglycemia is statistically significantly associated with reduced overall survival in survivors of early-stage breast cancer. Further study of diabetes and its relationship to breast cancer outcomes is warranted.
Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093-0901, USA.
Kirsten
K
Erickson
Ruth E
RE
Patterson
Shirley W
SW
Flatt
Loki
L
Natarajan
Barbara A
BA
Parker
Dennis D
DD
Heath
Gail A
GA
Laughlin
Nazmus
N
Saquib
Cheryl L
CL
Rock
John P
JP
Pierce
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000097:blood* / Q000150:complications* / Q000401:mortality; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications*; D018572:Disease-Free Survival; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006456:Hemoglobinuria / Q000097:blood; D006801:Humans; D008875:Middle Aged; D011379:Prognosis
D006442:Glycated Hemoglobin