Impact of diabetes mellitus on complications and outcomes of adjuvant chemotherapy in older patients with breast cancer

Abstract

Purpose: To evaluate whether diabetes affects patterns of adjuvant chemotherapy use, toxic effects of chemotherapy, and breast cancer outcomes.

Patients and methods: By using the Surveillance, Epidemiology, and End Results-Medicare database, we identified patients aged 66 years or older who had stages I through III breast cancer that was diagnosed between 1992 and 2002. Multivariable regression analyses were performed to determine the effect of diabetes on use of chemotherapy, toxicities, and outcomes. The risks of all-cause mortality and breast cancer-specific (BCS) mortality were estimated with the Kaplan-Meier method.

Results: Our cohort had 70,781 men and women, of whom 14,414 (20.36%) had diabetes. Among people who received chemotherapy (n = 11,826), 21.0% were diabetics. In this group, diabetics had lower odds of receiving anthracyclines (odds ratio [OR], 0.78; 95% CI, 0.71 to 0.87) and taxanes (OR, 0.86; 95% CI, 0.75 to 0.99). Diabetes was associated with increased odds of being hospitalized for any chemotherapy toxicity (OR, 1.38; 95% CI, 1.23 to 1.56), for infection or fever (OR, 1.43; 95% CI, 1.2 to 1.7), for neutropenia (OR, 1.22; 95% CI, 1.03 to 1.45), for anemia (OR, 1.24; 95% CI, 1.05 to 1.47), and for any cause (OR, 1.32; 95% CI, 1.19 to 1.46). Patients with diabetes had higher all-cause mortality (hazard ratio [HR], 1.35; 95% CI, 1.31 to 1.39). There was a significant interaction between diabetes and chemotherapy use for BCS mortality. Diabetic and nondiabetic patients who did not receive chemotherapy had similar BCS mortality, but diabetic patients who did receive chemotherapy had higher BCS mortality than nondiabetic patients (OR, 1.20; 95% CI, 1.07 to 1.35).

Conclusion: In this observational, hypothesis-generating study, patients who have breast cancer and diabetes are at increased risk of chemotherapy-related toxicities compared with nondiabetic patients who are receiving chemotherapy and have higher all-cause mortality.

Fig 1.

Unadjusted all-cause mortality curve of patients with and without diabetes and breast cancer. Five- and 10-year all-cause survival probabilities: 0.64 (95% CI, 0.63 to 0.65) and 0.37 (95% CI, 0.36 to 0.39), respectively, for patients with diabetes, and 0.75 (95% CI, 0.75 to 0.75) and 0.51 (95% CI, 0.50 to 0.52), respectively, for patients without diabetes (P < .0001 for each).

Fig 2.

Unadjusted breast cancer–specific (BCS) mortality curve of patients with and without diabetes and breast cancer who (A) received chemotherapy and who (B) did not receive chemotherapy.