School of Public Health

Gregory S. Calip

The association between cardiometabolic risk factors and breast cancer outcomes


Prevalence of cardiometabolic risk factors contributing to metabolic syndrome is common, and numerous metabolic syndrome components are associated with increased primary breast cancer risk. However, less is known about their relation to breast cancer outcomes. In addition, adherence to chronic medications for metabolic syndrome risk factors such as diabetes is generally low and associated with adverse health outcomes. The growing population of breast cancer survivors and increasingly high prevalence of comorbidity warrants better understanding of medication adherence and clinical management. We sought to evaluate whether metabolic syndrome risk factors increase risk of second breast cancer events (SBCE) and breast cancer-specific mortality and describe whether adherence to oral diabetes medications and clinical control of diabetes vary prior to and following breast cancer treatment.


We conducted a retrospective cohort study among female health plan enrollees ages ≥18 years diagnosed with stage I or II breast cancer between 1990-2008 via the Surveillance, Epidemiology, and End Results registry. Data sources included automated health plan data and medical records. We used Cox regression models to estimate the relation between metabolic syndrome components and SBCE (first of recurrence or second primary) and breast cancer-specific mortality while adjusting for potential confounders. We measured adherence and discontinuation of oral diabetes medications, biguanides (i.e., metformin) and sulfonylureas using medication possession ratios (MPR) and discontinuation rates (DR) in the year prior to incident cancer diagnosis, during treatment and the subsequent three years. We evaluated medication adherence (MPR ≥0.80), persistence (1-DR) and glycemic control (HbA1c ≤7.0%) in corresponding periods.


Among the 4,216 women in the cohort, 26% had ≥3 metabolic syndrome components and 13% developed SBCE during follow-up. Presence of metabolic syndrome (≥3 components) was associated with increased risk of SBCE (HR 1.50, 95% CI 1.08-2.07) and increased risk of breast cancer-specific mortality (HR 1.65, 95% CI 1.02-2.69). Among the 509 oral diabetes medication users, the proportion of adherent users declined during breast cancer treatment (75.3% versus 24.6%, P<0.001), whereas the proportion of high HbA1c (>7.0%) was increased in the year following treatment (34.9% versus 51.1%, P<0.001) compared with baseline.


Risk of SBCE and breast cancer-specific mortality may be altered by cardiometabolic risk factors contributing to metabolic syndrome. Adherence to oral medications for diabetes and glycemic control declines during and following breast cancer diagnosis. Further research in larger more diverse populations as well as other site-specific cancers and comorbidities is warranted.